Dr. Rao is associate professor and vice-chair in the Department of Psychiatry and Behavioral Neurosciences at Loyola University Medical Center in Maywood, Illinois.

Disclosures: Dr. Rao is on the speaker’s bureau of Forest.

Acknowledgments: The author thanks Maria Theodorou for her assistance in compiling the references used in this manuscript.

Please direct all correspondence to: Murali Rao, MD, DFAPA, FAPM, Associate Professor and Vice-Chair, Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, IL 60153; Tel: 708-216-3276; Fax: 708-216-5885; E-mail: mrao1@lumc.edu.

 


 

Focus Points

• Depression should not be discounted as an inevitable natural consequence  to a serious medical illness.
• The utility of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, in diagnosing depression in the medially ill is limited.
• Aggressive treatment of depression utilizing all available modalities along with the treatment of comorbid medical illnesses is important as it affects not only the patient’s improved participation in the treatment but also decreased morbidity.
• The overall effect on the course of the disease itself and mortality needs to be further studied.

 

Abstract

As depression is strongly associated with physical illness, it can be a complex and challenging condition for the medically ill. Approximately 33% of physically ill patients have depressive symptoms, many of which are regarded as understandable responses or reactions to the physical illness. Depressive illness is often under-diagnosed and under-treated, particularly in those with coexisting physical illnesses. The assessment of both conditions and the interaction between them is critical in managing these patients. Studies have clearly established that these depressive disorders are amenable to psychological or pharmacologic treatments.

 

Introduction

Depressed patients are more likely than non-depressed patients to have longer hospital stays and more outpatient visits, suffer greater disability, suffer from poorer quality of life, and experience suicidal thoughts and even commit suicide.

Major depression is at least twice as common in hospitalized medical patients compared to depression in the general population. The prevalence of major depressive disorder (MDD) in patients with comorbid medical illness can be as high as 30% in the hospital setting.1 Presence of comorbid depression is predictive of worse outcomes of medical illness and increased mortality.2 It may be better to risk over diagnosing depression than to leave depression untreated. Studies have shown that treatment of even minor or sub-syndromal depression has beneficial effects on the overall functioning of the physically ill individual and enhances treatment compliance for the co-existing medical illness and the recovery and rehabilitation process. It has been well established that in patients with type-2 diabetes, MDD is both a precursor as well as a comorbid illness. This is also the case in cerebrovascular and cardiovascular diseases.

 

The Association of Depression and Physical Illness

The association of depression and physical illness can be best understood as follows. First, depression can be caused by an underlying physical illness or be an exacerbated response3 or a reaction to the illness. Second, depression can be a consequence of treatment of physical illness with medications (eg, antihypertensives, corticosteroids, and other immunosuppressants) or cancer treatments, especially with interferons.4 Third, depression may be a consequence of various medical illnesses. Depression occurs in approximately 30% to 40% of patients with acute stroke or myocardial infarction, and has been linked to poorer cognitive and physical recovery. Fourth, depression can be a complication.3 Depression should be considered a new strong risk factor among other pre-existing risk factors, especially anxiety or panic states, through increased sympathetic activity; mobilization of free fatty acid from adipose tissue; thrombogenicity and platelet activation, agglutination; thrombus formation; and inflammation, particularly in coronary and cerebrovascular disorders; and possibly in other conditions. Fifth, depression may be a co-existant, pre-existant, or coincidental association3 to a physical illness. Sixth, depression can be contextual; it may be an effect of illness and its impact on life situations (eg, personal, job, relationships, finances) or in the context of metabolic disturbances (eg, hypoactive delirium presenting as depression). Seventh, depression may be a cue or clue to an underlying illness or a prelude to yet to be diagnosed major illness, especially in those who have the first onset of depression in mid-life or later. Approximately 33% of Alzheimer’s patients experience depression in the prodromal and early stages of dementia.5 Last, depression may be a contributing factor to the prolongation of the distress of a physical illness.

 

Detection of Depression

Detection of depression in the medically ill can be difficult for the following reasons.6 First, it may be regarded as a “normal: reaction to physical illness. Second, common vegetative symptoms include weight loss, fatigue, weakness, and anorexia often due to the medical illness. Third, it is difficult to distinguish onset of a depressive syndrome from psychological reactions to life-threatening illness. Last, the effects of impaired cognitive functioning secondary to the medical illness itself may detract from the detection of depression. As a result, the symptom pattern cannot be relied upon to a make a definitive diagnosis.7

To quote Dr. Elizabeth Scott8:

The reason for these disorders largely being unrecognized is fairly complex. But, certainly the conventional classification systems that we use in psychiatry contribute to this. Those classification systems are often not helpful in patients with physical illness. That’s because these systems largely depend on vegetative symptoms, as part of their diagnostic criteria. Symptoms such as sleep or appetite disturbance, changes in weight, changes in neuro-cognitive status, short-term memory or concentration, or changes in energy level also are symptoms of the underlying physical illness itself and then it becomes hard to tease out what’s the underlying physical illness or the disease process and what’s the contribution of depression or anxiety and also it makes it hard to gauge the severity of depressive or anxiety symptoms. Psychiatrists generally have a lack of agreement or consensus about the appropriate diagnostic criteria or classification systems to use in these patients…Physicians and patients themselves often assume that these symptoms are a reaction to the underlying physical illness, or…part of the disease process itself, so they often feel that they don’t merit separate identification assessment or intervention.

Screening instruments such as the Beck Depression Inventory cannot replace clinical assessment. When usual resilience to illness is replaced by pervasive low mood, depression characterized by lack of interest in life should be strongly suspected; empirical trial of treatment should be considered, especially in view of newer, safer antidepressants and psychological treatments.4 Although depression associated with medical illness has been shown to increase mortality, the benefits of treating depression on medical morbidity and mortality have yet to be established.9

 

Alternative Approaches to Help Detect Comorbid Depression

The Inclusive Approach

Instead of excluding symptoms appearing to be caused by a medical condition (eg, fatigue), the inclusive approach considers all symptoms describing depression. The inclusive approach is easy to use and sensitive to functional impairment.10

 

Substituting the “Classic” Vegetative Symptoms

Classic vegetative symptoms include change in appetite and sleep, fatigue and loss of energy, diminished ability to think or concentrate, indecisiveness, psychomotor slowing, tearfulness, depressed appearance, social withdrawal and decreased talkativeness, brooding, self-pity, pessimism, lack of reactivity to environmental events, and latency in responses.11

 

Modifying DSM-IV Criteria

One alternative approach to help detect comorbid depression is to modify the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition,12 to include the criteria in Table 1.13

 

 

Eliciting Positive Answers

Eliciting positive answers to the questions in Table 2 should raise awareness of the possibility of depression.

 

 

Asking Useful Questions

It is important to ask prime medical questions eliciting emotion and cognitive symptoms (Table 3).14 For example, during the past month, has the patient been frequently bothered by feeling down, depressed, or hopeless? During the past month, has he or she held little interest or experienced meager pleasure from certain activities? More simply, the patient could be directly asked if he or she felt sad or depressed, which seems to be the simplest and most yielding research question.

 

 

 

Prevalence Rates of Depression in Various Medical Conditions

As per the United States Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, the prevalence rates of depression in various medical conditions are listed in Table 4 and Figure 1.15-27

 

 

 

Cardiovascular System

According to Ginzburg, “the damage to the heart, with its symbolic meaning as the essence of the human being may shatter the patient’s sense of wholeness and safety.”28

Figure 2 shows cumulative mortality for depressed and non-depressed patients following a heart attack.29

 

As first reported by Frasure-Smith and colleagues,29 MDD in patients hospitalized following a myocardial infarction is an independent risk factor for mortality at 6 months and increases mortality 3–5 fold. Its impact is at least equivalent to that of left ventricular dysfunction and history of previous myocardial infarction.

A prospective cohort study by Surtees and colleagues30 found that MDD was associated with an increased risk of ischemic heart disease mortality. This association was independent of established risk factors for ischemic heart disease and remained undiminished several years after the original assessment.

One study31 has shown that, after acute coronary syndromes, depressed patients have elevated levels of inflammatory markers, thus suggesting chronic endothelial activation among these patients.

Depression may itself predispose to vascular disease. Mechanisms proposed for the linkage between depression and cardiovascular disease include the effects of hypercortisolemia (glucocorticoids inhibiting inflammation processes38 or by reducing glucocorticoid signaling leading to abnormal brain functioning32-24), immune activation, depression-related platelet aggregation leading to increased thrombosis, depression-induced impairment of arterial endothelial functioning, and abnormal folate or homocysteine metabolism. Although these mechanisms have been proposed to relate depression to cardiovascular diseases, depression could also be linked to cerebrovascular disease.32

 

Cerebrovascular System

Depression occurs in approximately 40% of patients with acute stroke and has been linked to poorer cognitive and physical recovery. An association between depressive symptoms and stroke mortality was reported by Morris and colleagues,35 who found that stroke patients with in-hospital depression were 3.5 times more likely to die during 10 years of follow up than patients without depression.

Treatment with fluoxetine or nortriptyline for 12 weeks during the first 6 months poststroke significantly increased the survival of both depressed and nondepressed patients. This finding suggests that the pathophysiologic processes determining the increased mortality risk associated with poststroke depression last longer than the depression itself and can be modified by antidepressants.36

Based on the above, one could wonder if depression is a “contributor or a consequence” of both cardiovascular and cerebrovasular pathologies (Figure 3).37,38 It remains possible that the high rate of depression in both conditions represents a common vascular mechanism.39

 

 

 

Cancer

The prevalence of depression among cancer patients ranges between 23% and 60%. Acute stress and anxiety and/or dysphoric states following discovery of cancer (a traumatic life event) are poorly understood in traditional medical settings. Pain and depression are the most common neuropsychiatric presentations, and they are followed by fatigue, distress, and various disabilities. As the disease progresses, immunologic changes and the effect of treatment could be an additional burden contributing to MDD. Increased levels of cytokines, (eg, interleukin) secreted by the immune system to fight cancer or infections could also result in “sickness behavior syndrome,” characterized by a depressed mood, sleepiness, and poor concentration (Figure 4).40 Higher than normal plasma IL-6 concentrations were associated with a diagnosis of MDD in cancer patients. IL-6 may contribute to sickness behavior that has overlapping symptoms with MDD.41

 

While helping to bolster the immunologic response, it is equally important to acknowledge the patient’s symptoms and treat them vigorously with cognitive-behavioral therapy, stress management, and antidepressant drug therapy.

 

Diabetes Mellitus

Depression as a precursor and as a consequence to type 2 diabetes has been studied. Prevalence of depression in adult diabetics is 3–5 times compared to prevalence in general population. Fourteen percent to 15% of patients diagnosed with type-2 diabetes have MDD. Thirty-three percent of all patients with neuropathy, retinopathy, and nephropathy are depressed. MDD in diabetes indicates poorer prognosis, worse glucose control, increased symptoms, decreased adherence to prescription plans, increased complications, decreased overall functional well being, and occasionally suicidality with complications.

Following a large population-based study in Norway, Engum and colleagues21 concluded that diabetes did not predict symptoms of depression or anxiety. Rather, symptoms of depression and anxiety emerged as significant risk factors for onset of type-2 diabetes independent of established risk factors for diabetes, such as socioeconomic factors, lifestyle factors, and markers of the metabolic syndrome.

The studies, presented at the meeting of the European Association for the Study of Diabetes,42 add to a growing body of evidence linking depression and other mental disorders to diabetes risk. Symptoms of depression or psychological stress were associated with increased risk of type-2 diabetes in men, but not in women, as per Swedish researchers.42 “People with diabetes had a higher prevalence of all mental illnesses compared with people without diabetes,” according to researchers from Canada.43 In particular, they noted that the rate of affective and anxiety disorders was >30% higher in people with diabetes who were <50 years of age. Other researchers have found hippocampal changes in patients with juvenile onset diabetes.

 

Neurologic Illnesses

Table 5 provides the rates of depression in neurologic illnesses.44

 

 

 

Aging, Frailty, and Alzheimer’s Disease

Physical frailty and need for assistance in daily living often causes dysphoria. However, depression should not be accepted as a normal part of aging, as untreated depression in the elderly causes needless suffering. Depression can render mild cognitive impairment to appear like dementia, thus confounding diagnosis and prognostication. A history of early onset depression increases the risk for Alzheimer’s disease compared to those with no history.45

 

HIV/AIDS

In addition to social stigma in the early stages, even when physically well, drug issues, HIV’s later physical effects of nausea and fatigue with anti-retro virals, HIV-related apathy, mood disorders, and cognitive impairments are seldom recognized early in the course of the disease. The cerebral events may remain compartmentalized and not necessarily reflected in the routine assessment of peripheral markers such as viral loads or T-cell counts.

 

Musculoskeletal Rehabilitation

See Table 6 for the prevalence of psychiatric disorders in musculoskeletal rehabilitation.46

 

 

 

Conclusion

In addition to the knowledge that depression contributes both to disability and diminished survival among medically ill, it is increasingly evident that MDD is a multi-systemic disorder that affects both brain and bodily functions.40

The inter-relationship between the two is rather complex. Inflammation could be the common link through neuro-immuno-endocrine mechanisms contributing to both psychological and somatic symptoms such as depression and cardiovascular diseases.27,47,48 As more evidence accumulates, it seems clear that late-onset depression in particular is not just a mood disorder but could be a warning signal of an impending major or catastrophic physical illness. It is well known that depression is a heralding symptom of undiagnosed medical conditions including multiple sclerosis, Parkinson’s disease, hypo- or hyperthyroidism, Cushing’s disease, and pancreatic cancer. The assessment of both conditions and the interaction between them is critical in managing these patients.1 When the medical illness is treated, the depression often gets better. While the importance of recognition and treatment of comorbid depression in helping reduce disability and suffering is very clear, the effect of treatment on the course of the comorbid illnesses themselves and the overall effect on survival need to be further studied. Also in need of further investigation are yet-to-be-discovered, non-antidepressant, disease-modifying effects of selective serotonin reuptake inhibitors or other newer agents on diabetes, stroke, multiple sclerosis, and Alzheimer’s disease (among other diseases).

Considering the available evidence, it is clearly prudent to include aggressive treatment of comorbid depression, utilizing all available modalities—including psychopharmacologic agents—in the management of all physical illnesses. PP

 

References

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3.    Peveler R, Carson A, Rodin G. Depression in medical patients. BMJ. 2002;325(7356):149-152.
4.    Rapp MA, Schnaider-Beeri M, Grossman HT, et al. Increased hippocampal plaques and tangles in patients with alzheimer disease with a lifetime history of major depression. Arch Gen Psychiatry. 2006;63(2):161-167.
5.    Wyszynski AA, Wyszynski B. Manual of Psychiatric Care for the Medically Ill. 1st ed. Washington, DC: American Psychiatric Publishing, Inc.; 2004.
6.    Hickie IB, Davenport TA, Naismith SL, Scott EM. SPHERE: a national depression project. SPHERE National Secretariat. Med J Aust. 2001;175(suppl):S4-S5.
7.    Royal College of Physicians of London and Royal College of Psychiatrists. The Psychological Care of Medical Patients: A Practical Guide. Wiltshire, England: Sarum ColourView Group; 2003.
8.    Scott E. Depression and Anxiety in the Medically Ill. SPHERE: A National Depression Project. Available at: www.spheregp.com.au. Accessed August 5, 2008.
9.    Kroenke K. Patients presenting with somatic complaints: epidemiology, psychiatric comorbidity and management. Int J Methods Psychiatr Res. 2003;12(1):34-43.
10.    Koenig HG, George LK, Peterson BL, et al. Depression in medically ill hospitalized older adults: prevalence, characteristics, and course of symptoms according to six diagnostic schemes. Am J Psychiatry. 1997;154:1376-1383.
11.    Endicott J. Measurement of depression in patients with cancer. Cancer. 1984;53(10 suppl):2243-2248.
12.    Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
13.    Cavanaugh S, Clark DC, Gibbons RD. Diagnosing depression in the hospitalized medically ill. Psychosomatics. 1983;24(9):809-815.
14.    Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ. 2003;327(7424):1144-6.
15.    Folks DG. The interface of psychiatry and irritable bowel syndrome. Curr Psychiatry Rep. 2004;6(3):210-215.
16.    Mikkelsen RL, Middelboe T, Pisinger C, Stage KB. Anxiety and depression in patients with chronic obstructive pulmonary disease (COPD). A review. Nord J Psychiatry. 2004;58(1):65-70.
17.    Krueger RF, Tackett JL, Markon KE. Structural models of comorbidity among common mental disor¬ders: connections to chronic pain. Adv Psychosom Med. 2004;25:63-77.
18.    Cruess DG, Petitto JM, Leserman J, et al. Depression and HIV infection: impact on immune function and disease progression. CNS Spectr. 2003;8(1):52-58.
19.    Iosifescu DV, Bankier B, Fava M. Impact of medical comorbid disease on antidepressant treatment of major depressive disorder. Curr Psychiatry Rep. 2004;6(3):193-201.
20.    Parker JC, Wright GE. The implications of depression for pain and disability in rheumatoid arthritis. Arthritis Care Res. 1995;8(4):279-283.
21.    Engum A, Mykletun A, Midthjell K, Holen A, Dahl AA. Depression and diabetes: a large population-based study of sociodemographic, lifestyle, and clinical factors associated with depression in type 1 and type 2 diabetes. Diabetes Care. 2005;28(8):1904-1909.
22.    Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB. Sex and depression in the national comorbidity survey. I: lifetime prevalence, chronicity and recurrence. J Affect Disord. 1993;29(2-3):85-96.
23.    Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the national comorbidity survey replication (NCS-R). JAMA. 2003;289(23):3095-3105.
24.    Evans DL, Staab JP, Petitto JM, et al. Depression in the medical setting: biopsychological interactions and treatment considerations. J Clin Psychiatry. 1999;60(suppl 4):40-55.
25.    Astrom M, Adolfsson R, Asplund K. Major depression in stroke patients. A 3-year longitudinal study. Stroke. 1993;24(7):976-982.
26.    Depression Guideline Panel. Depression in Primary Care: Vol 1. Detection and Diagnosis. Clinical Practice Guideline No. 5. Rockville, MD: US Department of Health; 1993.
27.    Depression in Primary Care: Vol 1. Detection and Diagnosis. Clinical Practice Guideline No. 5. Rockville, MD: US Dept of Health and Human Services. Public Health Service, Agency for Health Care Policy and Research; 1993: no. 93-0550.
28.    Porter V. Depression and Stress Hit Hard on the Heart. Medscape Cardiology. 2003: 7(1). Available at: www.medscape.com/viewarticle/449909. Accessed August 7, 2008.
29.    Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction. Impact on 6-month survival. JAMA. 1993;270(15):1819-1825.
30.    Surtees PG, Wainwright NW, Luben RN, Wareham NJ, Bingham SA, Khaw KT. Depression and isch¬emic heart disease mortality: evidence from the EPIC-norfolk United Kingdom prospective cohort study. Am J Psychiatry. 2008;165(4):515-523.
31.    Lesperance F, Frasure-Smith N, Theroux P, Irwin M. The association between major depression and levels of soluble intercellular adhesion molecule 1, interleukin-6, and C-reactive protein in patients with recent acute coronary syndromes. Am J Psychiatry. 2004;161(2):271-277.
32.    Kales HC, Maixner DF, Mellow AM. Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry. 2005;13(2):88-98.
33.    Pace TW, Hu F, Miller AH. Cytokine effects on glucocorticoid receptor function. Brain Behav Immun. 2007;21(1):9-19.
34.    Andrea Danese, Moffitt TE, Pariante CM, Ambler A, Poulton R, Caspi A. Elevated inflammation levels in depressed adults. Arch Gen Psychiatry. 2008;65(4):409-416.
35.    Morris PL, Robinson RG, Andrzejewski P, Samuels J, Price TR. Association of depression with 10-year poststroke mortality. Am J Psychiatry. 1993;150(1):124-129.
36.    Jorge RE, Robinson RG, Arndt S, Starkstein S. Mortality and poststroke depression: a placebo-controlled trial of antidepressants. Am J Psychiatry. 2003;160(10):1823-1829.
37.    Hays JC, Krishnan KR, George LK, Blazer DG. Age of first onset of bipolar disorder: demographic, family history, and psychosocial correlates. Depress Anxiety. 1998;7(2):76-82.
38.    Frasure-Smith N, Lesperance F. Depression and other psychological risks following myocardial infarction. Arch Gen Psychiatry. 2003;60(6):627-636.
39.    Aben I, Verhey F, Strik J, Lousberg R, Lodder J, Honig A. A comparative study into the one year cumula¬tive incidence of depression after stroke and myocardial infarction. J Neurol Neurosurg Psychiatry. 2003;74(5):581-585.
40.    Insel TR, Charney DS. Research on major depression: strategies and priorities. JAMA. 2003;289(23):3167-3168.
41.    Musselman DL, Miller AH, Porter MR, et al. Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am J Psychiatry. 2001;158(8):1252-1257.
42.    Östenson CG, Eriksson AK, Granath F, Hilding A, Efendic S, Ekbom A. Depressive symptoms and risk of type 2 diabetes and pre-diabetes in a prospective study of middle aged Swedish men and women. Paper presented at: 43rd Annual Meeting of the European Association for the Study of Diabetes; September 20, 2007; Amsterdam, Netherlands.
43.    Osterweil, N. Studies Link Depression and Type 2 Diabetes. EASD: European Association for the Study of Diabetes Meeting. MedPage Today. Reviewed by Agus, Z. Sept 21, 2007. Available at: www.medpagetoday.com/MeetingCoverage/EASD/tb/6752. Accessed August 7, 2008.
44.    Geerlings MI, den Heijer T, Koudstaal PJ, Hofman A, Breteler MM. History of Depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology. 2008:70(15):1258-1264.
45.    Schiffer RB. Goldman consensus statement on depression in MS. Goldman Consensus Group. Multiple Sclerosis. 2005;11:328-337.
46.    Harter M, Reuter K, Weisser B, Schretzmann B, Aschenbrenner A, Bengel J. A descriptive study of psychiatric disorders and psychosocial burden in rehabilitation patients with musculoskeletal diseases. Arch Phys Med Rehabil. 2002;83(4):461-468.
47.    Evans DL, Charney DS, Lewis L, et al. Mood disorders in the medically ill: scientific review and recommendations. Biol Psychiatry. 2005;58(3):175-189.
48.    Berkman LF, Blumenthal J, Burg M, et al. Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the enhancing recovery in coronary heart disease patients (ENRICHD) randomized trial. JAMA. 2003;289(23):3106-3116.

 

Dr. Levenson is professor in the Departments of Psychiatry, Medicine, and Surgery, chair of the Division of Consultation-Liaison Psychiatry, and vice chair for clinical affairs in the Department of Psychiatry at Virginia Commonwealth University School of Medicine in Richmond.

Disclosure: Dr. Levenson reports no affiliation with or financial interest in any organization that may pose a conflict of interest.

 


 

This column continues a series reviewing the interface between dermatology and psychiatry. Part one focused on atopic dermatitis and psoriasis.1 This second installment reviews alopecia areata, urticaria, and angioedema. Dermatologists and primary care physicians frequently encounter important psychiatric issues affecting diagnosis and management of the patient with dermatologic complaints. Psychiatrists contend with frequent pruritus and rashes in their patients. A study of psychiatric inpatients that excluded those with known skin diseases found that 33% of patients reported itching.2 Psychological factors affect many dermatologic conditions including atopic dermatitis, psoriasis, alopecia areata, urticaria and angioedema, and acne vulgaris. Some dermatologic conditions are best considered idiopathic functional disorders, such as idiopathic pruritus, which can be generalized or focal (eg, pruritus ani, vulvae, and scroti). Some primary psychiatric disorders present with primarily physical symptoms to dermatologists, including body dysmorphic disorder (BDD) and delusional disorder, somatic type (eg, delusions of parasitosis or of a foul body odor). Indeed, most patients with delusions of parasitosis or BDD avoid seeing psychiatrists or other mental health professionals and resist referral. Dermatologists also see patients with compulsive behaviors that may be part of obsessive-compulsive disorder (OCD), or stand alone (eg, trichotillomania, psychogenic excoriation, and onychophagia). Factitious skin disorders include factitious dermatitis (also called dermatitis artefacta) and psychogenic purpura. Another important aspect of the interface between psychiatry and dermatology is the range of dermatologic adverse reactions to psychotropic drugs.3,4

 

Alopecia Areata

Alopecia areata is characterized by nonscarring hair loss in patches of typically well-demarcated smooth skin, most noticeably on the scalp but the eyebrows, eyelashes, beard, and body hair can all be affected. Involvement varies from a single patch to multiple patches or total hair loss. It can affect the entire scalp (alopecia totalis) or cause loss of all body hair (alopecia universalis). Breakage of the hair shaft results in characteristic “exclamation-mark” hairs. The peak incidence of alopecia areata is in the third to fifth decades of life. It is a relatively common condition affecting 0.15% of the population. Approximately 1% of the United States population will have at least one episode by 50 years of age, with equal incidence in men and women. One-third of patients with alopecia areata completely recover after a single episode, but the rest have recurrences or never recover from the first episode. Although in many cases it can be a self-limiting condition, hair loss can often have severe social and emotional impacts.

 

Alopecia Areata and Stress

Alopecia areata was at one time considered a “psychosomatic illness” because of the apparent influence of stress on the disorder and the frequency of comorbid psychiatric symptoms. However, empirical literature has shown mixed results and debate continues about the role of psychiatric factors in the development of alopecia areata.3,4 Some recent studies described here will convey the complexity of the issues.

A case-control study comparing adults with alopecia areata to controls with skin diseases considered unaffected by stress reported that 66% of those with alopecia areata had experienced stressful events compared to 22% of controls (odds ratio=7.75). Alopecia areata patients also had a higher mean number of stressful life events. Especially common in patients with alopecia areata were family problems (45.6% of subjects) and personal problems (35.7% of subjects).5

Another cross-sectional case-control study6 of 52 adult patients diagnosed with alopecia areata and 52 age- and sex-matched individuals without any hair loss found no statistically significant difference between the patient and control groups with regard to the total scores of stressful major life events, depression, or anxiety. The total number of stressful life events was higher in patients who attributed their disease to a stressful life event than in those who did not, but this could either indicate that stressful life events may act as a trigger in a subset of patients, or a reporting bias. A similar case-control study7 found an increase in stressful life events in patients with recurrent alopecia areata but not in those with first episodes. A significantly higher degree of trait-anxiety and perceived distress were observed among patients in both alopecia groups compared to the control subjects, but these results do not allow any conclusions about causality.

 

Psychosocial Morbidity in Alopecia Areata

A small cross-sectional study8 found that 66% of patients with alopecia areata had psychiatric comorbidity, mainly adjustment disorders, generalized anxiety disorder, and depressive episodes. The patients’ overall adaptation to the illness was satisfactory, showing few adverse effects in family or social life, work, or sexual adjustment. Poor adjustment was associated with a dependent or antisocial personality, generalized anxiety, and depression.8

There has been little attention in the literature to the psychosocial consequences of alopecia areata in children. A small case-control cross-sectional study9 in children with alopecia areata compared with control children who visited a pediatrician “for a mild condition,” reported that the children with alopecia were more anxious, depressed, withdrawn, aggressive, and/or delinquent. They had more inattention, somatic complaints, and problems in social relations. Girls with alopecia appeared to more adversely psychologically affected than boys.

 

Alopecia Areata Treatments

A 2008 Cochrane review10 of treatment for alopecia areata concluded that very few treatments for alopecia areata have been well evaluated in randomized trials. No randomized controlled trials could be found establishing efficacy of the most commonly used oral or topical dermaceuticals. Most of the published trials are so small, brief, and flawed that any important clinical benefits are inconclusive. Delamere and colleagues10 concluded, “Considering the possibility of spontaneous remission especially for those in the early stages of the disease, the options of not being treated therapeutically or, depending on individual preference wearing a wig may be alternative ways of dealing with this condition.”

 

Psychiatric and Psychological Treatments for Alopecia Areata

Antidepressants have been reported in case reports to both cause and benefit alopecia areata.11-13 In a very small double-blind, placebo-controlled trial,14 patients taking imipramine 75 mg/day had significantly more hair regrowth than did control subjects, an effect that was independent of  reductions in anxiety or depression. There have also been case reports of alopecia areata associated with antipsychotics.15,16 Uncontrolled studies of psychotherapy and relaxation techniques have been promising in the treatment of alopecia areata, but more study is needed. A typical example is an open trial of hypnotherapy, added as a complementary treatment or used as the only treatment for alopecia areata. Hypnosis was reported to result in improvement in anxiety and depression. In addition, scalp hair growth of 75% to 100% was seen in 12 of 28 patients, 5 of whom relapsed.17

 

Urticaria and Angioedema

Urticaria (hives) is characterized by circumscribed, elevated, red, usually pruritic edematous patches (wheals) involving the superficial dermis. Angioedema occurs when the edema extends into deeper tissue layers. Urticaria and angioedema are a result of the release of histamine and other vasoactive substances from mast cells or basophils. Urticaria is common, with a peak incidence between 20–40 years of age, higher in women than men.3,4 Acute urticaria is usually caused by an allergic reaction or infection, resolving spontaneously or easily treated. Some chronic or recurrent urticarias are hereditary, and some are physically induced, such as cold, solar exposure or delayed pressure urticaria. The cause of chronic urticaria or angioedema cannot be identified in the majority of cases, though autoimmune pathogenesis is suspected. Approximately 33% of patients with chronic idiopathic urticaria have circulating functional autoantibodies, but their role in the disease is unclear. Chronic idiopathic urticaria often responds poorly to standard dermatological treatment. Chronic idiopathic urticaria resolves spontaneously in 30% to 55% of patients within 5 years,18 but some patients have persistent symptoms for many years.

 

Urticaria and Stress

It is widely believed that stress can precipitate acute urticaria, and contribute to the pathogenesis of chronic urticarias. In one study,19 81% of patients with chronic idiopathic urticaria believed that their illnesses were due to stress. Stress so often seemed a precipitant to angioedema that for many years clinicians referred to it as angioneurotic edema. However, the evidence base for this belief about stress inducing urticaria is rather limited. Small controlled retrospective studies found that patients with chronic urticaria were more likely to have been exposed to stressful life situations before disease onset than those with fungal skin infections20 or other skin diseases.21 A larger cross-sectional study compared patients with chronic idiopathic urticaria to those with tinea pedis. In the 6 months preceding disease onset, patients with chronic idiopathic urticaria had significantly more life events, higher impact from life events, more somatic symptoms, more severe insomnia, less family support, and more negative coping tendencies. Good ego function, better coping strategies, and family support were associated with decreased frequency of urticaria.22

There are more data regarding psychiatric comorbitity in patients with chronic idiopathic urticaria (CIU), documenting higher rates of symptoms of anxiety and depression than healthy controls.23-25 A Turkish study using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition found that 49% of CIU patients had at least one Axis I diagnosis, and 45% had at least one personality disorder. The most common Axis I disorder was OCD (26%), and the most common Axis II disorder was obsessive-compulsive personality disorder (30%). OCD, major depressive disorder, and obsessive-compulsive and avoidant personality disorders were all more prevalent compared to a healthy control group.26

A similar study in Turkey22 found that 60% had psychiatric disorders, 66% of which were depressive disorders.19 The relationship between chronic idiopathic urticaria and anxiety/depression is likely bidirectional. One possible intervening factor is that both cause insomnia.22

Health-related quality of life  is markedly reduced in CIU patients,19,23,27,28 to an extent comparable to that of patients with chronic heart disease.28 Quality of life is significantly more impaired in chronic urticaria patients with psychiatric comorbidity, but is not significantly affected by age, sex, the absence or presence of angioedema, or the course or cause of the urticaria.27

 

Treatment of Chronic Urticaria

The first step in treatment is the avoidance of identifiable underlying causative or exacerbating factors. Histamine (H) receptor antagonists remain the mainstay of oral treatment for all forms of urticaria.18 Second-generation less sedating antihistamines (loratadine, fexofenadine, and cetirizine) are first-line agents.29 Sedating antihistamines like diphenhydramine are useful for the control of chronic idiopathic urticaria if itching is causing sleep disturbance. The tricyclic antidepressant doxepin is a potent H1 and H2 antihistamine, and is considered a standard treatment option for chronic urticaria.18,30 It has been found effective at low dosage for chronic urticaria in two small randomized controlled trials, one comparing it to placebo31 and one comparing it to diphenhydramine.32 In the latter trial,32 doxepin 10 mg TID was more effective than diphenhydramine 25 mg TID. It would be especially suitable for patients with comorbid depression. It remains controversial whether the addition of an H2 receptor antagonist or a leukotriene antagonist is helpful.18 For CIU, second-line agents include cyclosporine (effective in approximately 75% of patients), oral corticosteroids, intravenous immunoglobulins, and plasmapheresis.18,30

There has been only one controlled study33 of psychological treatment of chronic idiopathic urticaria, in which hypnosis combined with relaxation techniques reduced pruritus but not the number of wheals. PP

 

References

1. Levenson JL. Psychiatric Issues in Dermatology, Part 1: Atopic Dermatitis and Psoriasis. Primary Psychiatry. 2008;15(7):35-38.
2. Mazeh D, Melamed Y, Cholostoy A, Aharonovitzch V, Weizman A, Yosipovitch G. Itching in the psychiatric ward. Acta Derm Venereol. 2008;88(2):128-131.
3. Arnold L. Dermatology. In: Levenson JL, ed. American Psychiatric Publishing Textbook of Psychosomatic Medicine. American Psychiatric Publishing, Washington, DC, 2005:629-646.
4. Arnold L. Dermatology. In: Levenson JL, ed. Essentials of Psychosomatic Medicine. Washington, DC: American Psychiatric Publishing; 2007:237-260.
5. Manolache L, Benea V. Stress in patients with alopecia areata and vitiligo. J Eur Acad Dermatol Venereol. 2007;21(7):921-928.
6. Güleç AT, Tanriverdi N, Dürü C, Saray Y, Akçali C. The role of psychological factors in alopecia areata and the impact of the disease on the quality of life. Int J Dermatol. 2004;43(5):352-356.
7. Brajac I, Tkalcic M, Dragojevi DM, Gruber F. Roles of stress, stress perception and trait-anxiety in the onset and course of alopecia areata. J Dermatol. 2003;30(12):871-878.
8. Ruiz-Doblado S, Carrizosa A, García-Hernández MJ. Alopecia areata: psychiatric comorbidity and adjustment to illness. Int J Dermatol. 2003;42(6):434-437.
9. Liakopoulou M, Alifieraki T, Katideniou A, et al. Children with alopecia areata: psychiatric symptomatology and life events. J Am Acad Child Adolesc Psychiatry. 1997;36:678-684.
10. Delamere FM, Sladden MM, Dobbins HM, Leonardi-Bee J. Interventions for alopecia areata. Cochrane Database Syst Rev. 200816;(2):CD004413.
11. Ricciardi A, Ruberto A, García-Hernández MJ, et al. Alopecia areata with comorbid depression: early resolution with combined paroxetine-triamcinolone treatment. J Eur Acad Dermatol Venereol. 2006;20(8):1000-1001.
12. Ruiz-Doblado S, Carrizosa A, García-Hernández MJ, Rodríguez-Pichardo A. Selective serotonin re-uptake inhibitors (SSRIs) and alopecia areata. Int J Dermatol. 1999;38(10):798-799.
13. Parameshwar E. Hair loss associated with fluvoxamine use. Am J Psychiatry. 1996;153(4):581-582.
14. Perini G, Zara M, Cipriani R, et al. Imipramine in alopecia areata. A double-blind, placebo-controlled study. Psychother Psychosom. 1994;61(3-4):195-198.
15. Kubota T, Ishikura T, Jibiki I. Alopecia areata associated with haloperidol. Jpn J Psychiatry Neurol. 1994;48(3):579-581.
16. Kubota T, Ishikura T, Jibiki I. Three cases of alopecia areata induced by zotepine. Acta Neurol (Napoli). 1993;15(3):200-203.
17. Willemsen R, Vanderlinden J, Deconinck A, Roseeuw D. Hypnotherapeutic management of alopecia areata. J Am Acad Dermatol. 2006;55(2):233-237.
18. Kozel MM, Sabroe RA.Chronic urticaria: aetiology, management and current and future treatment options.Drugs. 2004;64(22):2515-2536.
19. Ozkan M, Oflaz SB, Kocaman N, et al. Psychiatric morbidity and quality of life in patients with chronic idiopathic urticaria. Ann Allergy Asthma Immunol. 2007;99(1):29-33.
20. Fava GA, Perini GI, Santonastaso P, et al. Life events and psychological distress in dermatologic disorders: psoriasis, chronic urticaria and fungal infections. Br J Med Psychol. 1980;53:277-282.
21. Lyketsos GC, Stratigos J, Tawil G, et al. Hostile personality characteristics, dysthymic states and neurotic symptoms in urticaria, psoriasis and alopecia. Psychother Psychosom. 1985;44:122-131.
22. Yang HY, Sun CC, Wu YC, Wang JD. Stress, insomnia, and chronic idiopathic urticaria-a case-control study. J Formos Med Assoc. 2005;104(4):254-263.
23. Engin B, Uguz F, Yilmaz E, Ozdemir M, Mevlitoglu I.The levels of depression, anxiety and quality of life in patients with chronic idiopathic urticaria. J Eur Acad Dermatol Venereol. 2008;22(1):36-40.
24. Brzoza Z, Kasperska-Zajac A, Badura-Brzoza K, et al. Decline in dehydroepiandrosterone sulfate observed in chronic urticaria is associated with psychological distress. Psychosom Med. 2008;70(6):723-728
25. Conrad R, Geiser F, Haidl G, et al. Relationship between anger and pruritus perception in patients with chronic idiopathic urticaria and psoriasis. J Eur Acad Dermatol Venereol. 2008 Mar 18. [Epub ahead of print]
26. Uguz F, Engin B, Yilmaz E.Axis I and Axis II diagnoses in patients with chronic idiopathic urticaria. J Psychosom Res. 2008;64(2):225-229.
27.  P, Eckhardt-Henn A, Dechene M, et al. Quality of life in patients with chronic urticaria is differentially impaired and determined by psychiatric comorbidity. Br J Dermatol. 2006;154(2):294-298.
28. O’Donnell BF, Lawlor F, Simpson J, et al. The impact of chronic urticaria on the quality of life. Br J Dermatol. 1997;136:197-201.
29. Grob JJ, Lachapelle JM. Non-sedating antihistamines in the treatment of chronic idiopathic urticaria using patient-reported outcomes. Curr Med Res Opin. 2008 Jul 22: epub ahed of print.
30. Fromer L.Treatment options for the relief of chronic idiopathic urticaria symptoms. South Med J. 2008;101(2):186-192.
31. Goldsobel AB, Rohr AS, Siegel SC, et al. Efficacy of doxepin in the treatment of chronic idiopathic urticaria. J Allergy Clin Immunol. 1986;78(5 Pt 1):867-873.
32. Greene SL, Reed CE, Schroeter AL: Double-blind crossover study comparing doxepin with diphenhydramine for the treatment of chronic urticaria. J Am Acad Dermatol. 1985;12:669-675.
33. Shertzer CL, Lookingbill DP. Effects of relaxation therapy and hypnotizability in chronic urticaria. Arch Dermatol. 1988;123:913-916.

e-mail: ns@mblcommunications.com

 

Dr. Sussman is editor of Primary Psychiatry as well as professor of psychiatry and interim chairman in the Department of Psychiatry at the New York University School of Medicine in New York City.

Dr. Sussman reports no affiliation with or financial interest in any organization that may pose a conflict of interest.


 

It seems logical that someone with a chronic medical illness would become depressed as a consequence of prolonged pain, suffering, disability, or all of these, coupled with doubts about the prospects of recovery. Yet, there is surprisingly little discussion about depression as a natural consequence of a serious medical illness. Murali Rao, MD, DFAPA, FAPM, reviews some of the shortcomings in the current approaches to this patient population. Rao reports that approximately 33% of physically ill patients have depressive symptoms and major depressive disorder is at least twice as common in hospitalized medical patients compared to depression in the general population. However, he notes that one major limitation is the lack of guidance on diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision1 with respect to depression in the medically ill. As a result, depressive illness is often under-diagnosed and under-treated in those with coexisting physical illnesses. The assessment of both conditions and the interaction between them is critical in managing these patients. Rao describes approaches to diagnosis in these cases and recommends therapeutic interventions.

Another important topic is dyspareunia. As with many aspects relating to sexual function and dysfunction, the diagnosis and management of pain associated with sex is typically neglected in all phases of medical education. This leads to under-diagnosis and delays in treatment. As noted by Sharon Butcher, MD, and Frank W. Ling, MD, pain with intercourse, ie, dyspareunia, is a common disorder affecting a large percentage of women. As noted by the authors, approximately 50% of all female patients have complaints related to sexuality, yet only 18% of practitioners report routinely obtaining a sexual history. There are effective treatments available, but these need to be tailored to the individual patient and her idiosyncratic circumstances. They review the various causes of pain associated with sex and the types of physical examination associated with each of the anatomic causes of pelvic pain. They also clarify the benefits and risks the roles of medical and surgical treatment play in the management of pain with sex.

Recent articles2,3 have discussed the intense research interest in drugs that work on the glutamate system. A major impetus for this work has come from evidence that the anesthetic agent ketamine can have beneficial mood effects in patients with severe, longstanding depression, Stephen Ross, MD, discusses another aspect of ketamine and addiction. He reviews ketamine’s 4-decade history of safe and effective use as an anesthetic agent, as well as its history as a drug of abuse. The article includes a brief historic review of research and use of ketamine for a variety of medical and psychiatric conditions; a discussion of the addictive liability of ketamine, including biologic mechanisms; the potential anti-addictive properties of ketamine with an exploration of biologic and psycho-spiritual mechanisms of action; and the effects of drugs of abuse, in particular alcohol. Ross speculates that application of ketamine, in conjunction with addiction psychotherapy, could prove to be an effective and reliable treatment for substance abuse.

Rosemary Basson, MD, offers a new conceptualization of women’s sex response that reflects current data. These include the broad range of women’s sexual desire and its overlap with subjective sexual arousal, as well as the common lack of correlation between desire and subjective arousal on the one hand and objective increases in genital congestion on the other. Basson presents recommendations to revise official definitions of women’s sexual disorders of desire and arousal. After addressing any mental health or interpersonal issues, she suggests that combinations of psychoeducation, cognitive-behavioral therapy, and sex therapy are available. Mindfulness techniques are presented as promising interventions. Identification of women whose sexual disorder is based on deficiency of sex hormone activity remains challenging. The author concludes that testosterone supplementation for loss of both initial and triggered desire requires investigation. She describes other investigational pharmacologic adjuncts for treating genital sexual arousal disorder.

The impetus behind Marc Galanter, MD, and colleagues’ article on addressing patients’ spirituality in medical treatment is derived from the following sources. First, there is a requirement of spiritual assessment of patients by the Joint Commission on Accreditation of Hospital Organizations; second, there have been recent publications in the medical literature pointing to the need for increased attention to this issue; third, there has been concern over this issue among colleagues at New York University and in national medical organizations. The authors note that many patients have strong spiritually grounded feelings related to their ability to cope with illness. They summarize the role of spiritually oriented programs in terms of programs that are specifically religiously oriented. Such interventions may be effective in improving patients’ outlook on their medical care, as well as their ability to identify with the mission of hospital staff, thereby promoting greater compliance with the treatment regimens proposed. PP

 

References

1.    Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
2.    aan het Rot M, Charney DS, Mathew SJ. Intravenous ketamine for treatment-resistant major depressive disorder. Primary Psychiatry. 2008;15(4):39-47.
3.    Mathew SJ, Sussman N. In session with Sanjay J. Mathew, MD: ketamine: new pathways of medication. Primary Psychiatry. 2008;15(6):31-34.

 

Dr. Kornstein is professor of Psychiatry and Obstetrics/Gynecology, executive director of the Institute for Women’s Health, and executive director of the Mood Disorders Institute at Virginia Commonwealth University in Richmond. Dr. Culpepper is professor and chairman in the Department of Family Medicine at Boston University Medical Center in Massachusetts.

Disclosures: Dr. Kornstein is on the advisory boards of or receives honoraria from Biovail, Bristol-Myers Squibb, Eli Lilly, Forest, Neurocrine, Pfizer, Sepracor, and Wyeth; and receives research support from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, the Department of Health and Human Services, Eli Lilly, Forest, the National Institute of Mental Health,  Novartis, Sanofi-Synthelabo, Sepracor, and Wyeth. Dr. Culpepper is a consultant to Eli Lilly, Forest, Pfizer, and Wyeth; and on the speaker’s bureaus of Forest, Pfizer, and Wyeth.

Acknowledgments: The authors would like to thank Grant Steen, PhD, for his assistance.

Please direct all correspondence to: Susan G. Kornstein, MD, Dept of Psychiatry, Virginia Commonwealth University, PO Box 980710, Richmond, VA 23298-0710; Tel: 804-828-5637; Fax: 804-828-5644; E-mail: skornste@vcu.edu.

 

 

Abstract

 

According to recent data, women are at increased risk for depression during the menopausal transition, even in the absence of a psychiatric history. As a result, it is important to identify biologic, psychiatric, and social risk factors for depression. An English language electronic literature search using the PubMed database (1986–2006) was conducted using the search terms depression, depressive, depressed, menopause, perimenopause, postmenopause, and climacteric. Relevant references were extracted and summarized. The authors of this article identified risk factors for menopausal depression reported in at least two primary references. It was found that a variety of biologic, psychiatric, and psychosocial factors interact to increase vulnerability to depression during the menopausal transition. These findings are consistent with a biopsychosocial model for perimenopausal depression. Depression in the context of the menopausal transition may be difficult to recognize. Thus, physicians should be aware of the various factors that can increase an individual patient’s risk for illness during this time period.

 

Introduction

Currently, 21.5 million women 45–54 years of age live in the United States1 and virtually all of these women will have entered menopause within the next decade. Crude calculation suggests that nearly 2 million American women per year will go through the menopausal transition. The life expectancy of women is now approximately 80 years, so many women will live 33% of their lives after menopause.2 Successful transition into menopause enhances health-related quality of life3,4 and may increase satisfaction in the postmenopausal phase.4

This article will summarize relevant evidence regarding the risk of depression during the menopausal transition and discuss contributing factors that can assist clinicians in diagnosing and treating depression in midlife women. The authors conducted an electronic literature search using the PubMed database (1986–2006; English language) using the search terms depression, depressive, depressed, menopause, perimenopause, postmenopause, and climacteric. Relevant references (and cross-references) were extracted and summarized. Risk factors for menopausal depression reported in at least two primary references were identified.

 

The Menopausal Transition

The Stages of Reproductive Aging Workshop (STRAW) standardized terminology relating to menstruation and menopause.5 The final menstrual period typically occurs when women are 42–58 years of age (mean age=52), and this event is the zero point for the STRAW staging system. Menarche marks entry into the reproductive phase of a woman’s life (Stage –5, relative to the zero point), after which it can take several years for a regular menstrual cycle to become established. Reproductive maturity is associated with menstrual periods that occur every 21–35 days (Stages –4 and –3), with the late reproductive stage (Stage –3) characterized by a gradual increase in levels of follicle-stimulating hormone (FSH). The early menopausal transition (Stage –2) begins when rising FSH levels lead to variability in menstrual cycle length, with cycles varying by >1 week from the normal cycle length. The late phase of the menopausal transition (Stage –1) is associated with higher levels of FSH and greater variability of the cycle, with ≥2 skipped cycles and an interval of amenorrhea lasting at least 60 days (Figure 1).5

 

Female reproductive senescence is defined by the depletion of oocytes in the ovary,5 and reproductive aging thus consists of a progressive loss of oocytes through atresia or ovulation. Menopause begins at the final menstrual period, but this point cannot be recognized with surety until after 12 months of amenorrhea. The early postmenopause (Stage +1) lasts 5 years and includes the 12-month period of amenorrhea that defines the beginning of the menopause. The late postmenopause (Stage +2) lasts for the rest of a woman’s life. Many menopausal symptoms, especially vasomotor symptoms such as hot flashes, are most severe during Stage –1 or Stage +1, in what has been called the “perimenopause.”5

The transition to menopause is a normal facet of aging, and most women do not become clinically depressed during this phase.6 However, for some women it may be associated with mood changes, including depressive symptoms—similar to other reproductive life events associated with hormonal fluctuations, including the premenstrual phase of the cycle,7-10 pregnancy,11-13 and the postpartum period.8,12,14-17 Understanding and recognizing physical, psychosocial, and psychiatric factors that increase the risk for depression during the menopausal transition and how these factors interact to modulate the risk imparted by the menopausal transition itself is important, particularly for primary care physicians (PCPs) who are likely to be confronted by these issues frequently as increasing numbers of women approach menopause.

 

Risk of Depression During the Menopausal Transition

The menopausal transition is often associated with an increase in depressive symptoms,18-22 and recent evidence suggests that the transition to menopause is a risk factor for depression in and of itself.17,23 In fact, the menopausal transition has been associated with an increased risk of depression in women with or without a previous history of depression.

A prospective study following 29 asymptomatic premenopausal women through the transition to menopause examined the relationship between the onset of depressive symptoms and perimenopause.24 The study found that the risk of depression during the 2-year period centered at the final menstrual period was 14-fold higher than risk during a 31-year premenopausal phase, and that a psychiatric history was not necessary for women to experience depression during this time.

More recently, two studies examined the risk for perimenopausal depression in women with no prior history of mood disturbance, with consistent findings. One study included 460 premenopausal women, who were followed prospectively for 3 years; menopausal status was determined every 6 months based on menstrual cycle changes ascertained through patient interviews.17 Among women who entered the menopausal transition, 32.5% had a new onset of depressive symptoms, whereas 20.0% of women who remained premenopausal became depressed. The adjusted odds ratio (OR) for depression among women who entered the perimenopause was 1.8, compared with premenopausal women.17 Findings were similar when a more stringent definition of depression was applied. The adjusted OR for severe first onset of depression (defined as women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]25 criteria for major depressive disorder (MDD), self-reported depression most of the day nearly every day plus symptoms of anhedonia, or had a Center for Epidemiologic Studies Depression Scale score >24) in perimenopausal women compared with premenopausal women was 1.9, with incidence rates of 16.6% versus 9.5%, respectively.

The other study, an 8-year longitudinal study of 436 women, found that high depression scores were 4-fold more likely to occur during the menopausal transition (again determined based on menstrual cycle changes), relative to the premenopausal phase (P<.001).23,26 Increased levels of FSH and luteinizing hormone (LH) as well as increased variability of estradiol, FSH, and LH were all correlated with depressive symptoms. In a multivariate model, depressed women were 4.6-fold more likely to have elevated FSH levels and 3.0-fold more likely to have elevated LH levels (P<.002, for both).23 These relationships remained significant after adjusting for smoking, vasomotor symptoms, poor sleep, health status, employment, and marital status.

Studies that have included women with prior psychiatric diagnoses have found that those with a history of MDD prior to menopause are at particularly high risk for development of depression in the perimenopausal period.26-28 In addition, a history of prior depression related to the reproductive cycle, including premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), ovarian cancer-related dysphoria, and/or postpartum MDD is associated with depression during the menopausal transition.29-31

Taken together, these findings suggest that the changing hormonal milieu during the menopausal transition is associated with onset of depression, even among women with no history of mood disturbance. Furthermore, some women may be particularly vulnerable to developing depression during times of hormonal flux. However, the risk for depression during the menopausal transition is influenced by multiple factors, which will be discussed in more detail below.

 

Risk Factors for Depression During the Menopausal Transition

Women at midlife face a unique set of circumstances including physical changes related to aging in general and to the menopause in particular, psychosocial adjustments related to changing roles and responsibilities within the family, and a variety of potential life stressors.32 These issues, in addition to psychiatric considerations (eg, history of or current mood or anxiety disorder), have an impact on the likelihood of depression in women as they transition to menopause.33

 

Physical Context of the Menopausal Transition

Hormonal changes, such as the widely fluctuating hormone levels that are the hallmark of the menopausal transition,32 may be associated with mood changes. Hormonal fluctuations may have direct effects on mood. Although the mechanism is poorly understood, preclinical studies suggest that estrogen has effects on areas of the brain involved in regulation of mood including the prefrontal/frontal cortex, hippocampus, amygdala, hypothalamus, dorsal raphe, and locus coeruleus.34-36 Specifically, estrogens have been reported to influence monoamine systems via modulation of the firing rate, synthesis, release rate, and elimination pathways.37-44 There may also be indirect effects; for example, physical symptoms related to menopause, including hot flashes and insomnia, may be problematic enough to affect mood in a kind of “domino effect” of menopause-related depression.31 Alternatively, complications in the management of chronic medical conditions or comorbidities may also contribute to the risk of depression during the menopausal transition.

Ovarian hormones or fluctuations in hormone levels have been implicated in the regulation of mood and behavior.44 For example, women have about twice the risk of depression as men,15,27 and analysis of the age at onset of depression shows that the risk difference between females and males arises in early adolescence and persists through the mid-50s,27 roughly the ages that correspond to menarche and menopause. Furthermore, psychiatric illnesses—including depression, anxiety, bipolar disorder, schizophrenia, bulimia nervosa, and substance abuse—can undergo cyclic fluctuations in symptom severity, with worsening of symptoms during the premenstrual period.8 These exacerbations may reflect the intensification of an underlying psychiatric disorder and/or the onset of symptoms that occur only during the premenstrual phase of the cycle. In addition, hormonal fluctuations during the postpartum period can also lead to mood disturbance.45 During the menopausal transition, acute hormonal changes that occur during a normal menstrual cycle are superimposed upon gradual menopause-related changes in hormones.46 This hormonal unpredictability can potentially intensify the emotional lability that is a natural part of the menstrual cycle.

As previously mentioned, there is an increased risk of clinical depression associated with the menopausal transition.19,21,26,32,47-51 Yet, the heightened risk of depression related to menopause is transitory19 and changes over time, concurrent with the hormonal changes characteristic of each stage of the menopausal transition. Recent results suggest that the risk of depression increases during early to late perimenopause, but decreases afterward.26,52 The likelihood of depressive symptoms is lower for women with a rapidly increasing FSH profile.26 Since rapid changes in FSH are associated with a relatively short duration of the menopausal transition, this evidence is consistent with the finding that depression is less of a problem if the menopausal transition takes no longer than 27 months.19

In some women of reproductive age there is a cyclic exacerbation of chronic medical conditions during the menstrual cycle, including migraine, epilepsy, asthma, diabetes, rheumatoid arthritis, and irritable bowel syndrome, that is thought to be related to rapid changes in concentrations of circulating ovarian steroids.9,53,54 Likewise, the hormonal fluctuations associated with the menopausal transition may exacerbate symptoms or complicate management of some chronic medical conditions.54-57 Such challenges may have a negative impact on mood for some women.

Approximately 40% of women seek medical attention to alleviate symptoms of the menopausal transition.58 Physical complaints associated with the hormonal fluctuations of the perimenopause include headache, insomnia, vasomotor symptoms (eg, hot flashes and night sweats), and genital atrophy. Hot flashes are the core symptom that reflect the brain’s response to the changing hormonal milieu, particularly fluctuating levels of estrogen.59 Evidence shows that vasomotor symptoms are strongly associated with depression during the menopausal transition. In a cohort of 309 women followed prospectively for 3 years, hot flashes and night sweats increased the odds of depression 1.8-fold and insomnia increased the odds of depression 4.0-fold.18 In another study, perimenopausal women with vasomotor symptoms were 4.4-fold more likely to be depressed than were women without vasomotor symptoms.21

 

Psychosocial Context of the Menopausal Transition

Depression at the menopausal transition may not necessarily be precipitated only by changes in hormones. Many women have a subjective experience of loss or “exit events” at this time, as children mature and leave the home, living circumstances change, elderly parents become ill or pass away, and marriages evolve or end.32 Race and ethnicity appear to influence the risk for depression in middle-aged women until adjustment is made for psychosocial factors such as poverty, at which point racial and ethnic differences are no longer significant.60 In general, having a social support network is protective from depression, whereas a sense of loss of control is a risk factor.61 In some studies, the importance of social factors such as inadequate income was greater than menopausal status in causing depression.20 Although the number of women living alone increases with age, many women report an improvement in mood after the last child leaves the home.62

Adverse life events can have a powerful impact on the risk of depression during the menopausal transition.17,31,63,64 Stressful life events, especially those of a chronic nature, generally increase the risk of depression.33 In addition, women with high levels of trait anxiety or a pessimistic outlook are more prone to depression and more vulnerable to stressful life events.63 Women with negative life events, low self-esteem, a troubled relationship with a life partner or children, or a weak social support network are at greater risk for depression.64 Presence of adverse life events increases the risk of depression during the menopausal transition by approximately 26% compared with women without such events, and the risk is even greater if the life events occur against a background of vasomotor symptoms.17 In short, life stressors such as aging, general health problems, caring for elderly parents, marital problems, career changes, children leaving home, and other life losses may contribute to depression, completely apart from other biologic and psychiatric risk factors.

A prospective cohort study investigated the determinants of depression in Dutch women going through the menopausal transition, after excluding women who used hormone therapy or who were status post hysterectomy or oophorectomy.50 Self-reported depressive symptoms from 2,103 women were analyzed to determine which social factors correlated with depression. A range of social factors was found to increase the risk of depression significantly. The OR for depression was higher in the context of job loss or unemployment (OR=3.1), inability to work (OR=1.7), financial difficulties (OR=2.9), death of a life partner (OR=2.6), death of a child (OR=5.9), or having a previous episode of depression (OR=2.0). It is important to note that because history of MDD was via self-report in this study, some women may have had earlier depressive episodes that remained undiagnosed (and thus were not reported); in addition, recall of social factors (eg, divorce, job loss) was likely to be stronger. Other studies, which will be reviewed in more detail in the next section, have shown stronger associations between psychiatric history and risk during the menopausal transition. Nevertheless, these data provide a clear demonstration of the importance of social factors in depression during menopausal transition.

Another important factor that contributes to the risk of depression is a woman’s attitude toward menopause. While research in the United States tends to focus on the negative aspects of menopause, some cultures are more attuned to the positive outcomes of the menopausal transition.46 For example, in certain African tribes, women are said to relish the increase in freedom and social influence that is attained after menopause.46 Menopause frees women from the burden of childbirth, the worries of contraception, and the cultural restrictions that may apply to women who still menstruate. Many reports suggest that the psychological reaction of women to menopause reflects the values of the society in which they live, and the social status assigned to aging women.46

 

Psychiatric Risk Factors for Depression During the Menopausal Transition

Psychiatric History
The most significant risk factor for developing depression during the menopausal transition is a history of depression.19 A 5-year longitudinal study tracked 2,565 women and found that prior depression is the single best predictor of depression during the menopausal transition, with an adjusted OR of 9.6 (P<.0001).19 Prior depression was a better predictor than was use of hormone replacement therapy (OR=1.0), stage of menopause (OR<2.1), or menopausal symptom severity (OR=3.6). In addition, women who became depressed during a prior reproductive event are at greater risk of menopause-related depression.28-31 For example, women with a history of severe PMS or PMDD appear to be more likely to suffer from depression during the menopausal transition.30,31,51 Interestingly, women with a lifetime history of MDD may be more likely to show an early decline in ovarian function,17,22 suggesting that the relationship between mood and the reproductive system is bi-directional (ie, hormonal changes associated with reproductive life events can influence mood and the presence of mood disorder can influence reproductive life events).


Genetic Factors

Although there has been no research specifically focused on a potential genetic risk for depression during the menopausal transition, genetic factors have been shown to interact with stress to influence the risk for depression. A study of 549 male and female twins found an interaction between stressful life events and a genetic liability for depression.65 Twins with one specific form of the serotonin transporter gene were at significantly greater risk of depression following common life stressors. Twins having alternative forms of the serotonin transporter gene were at lower risk.65 These results replicate an earlier prospective longitudinal analysis of a birth cohort which also found a functional polymorphism in the promoter region of the serotonin transporter gene that varies in a way that moderates the effect of stress on depression.66 People with one specific allele of the serotonin promoter were more likely to show depressive symptoms in relation to stressful life events. This vulnerability revealed a gene-by-environment interaction (ie, an individual’s response to the environment is moderated by their genetic makeup).66 A third analysis of the association between functional variation in the serotonin protein and depression confirmed that people with one particular variant of this gene are at increased risk of depression following relatively mild stressors.65

A second possible genetic component is a potential genetic vulnerability related to the menopausal transition. Although there is not yet direct evidence of a genetic risk specific to menopause, there is evidence demonstrating a genetic component related to premenstrual symptoms that is largely independent of the risk for MDD. Studies investigating the heritability of menstrual and premenstrual symptoms found that the environmental and genetic risk factors for premenstrual symptoms were not closely related to those associated with lifetime MDD.67,68 A similar phenomenon may be associated with other reproductive events including the menopause, ie, there may be a genetic predisposition to depressive symptoms during the menopausal transition.

Neuroendocrine Effects of Estrogen
Estrogen is known to have very powerful neuroendocrine effects in the brain. Acute increases in estrogen can blunt the response to stress, whereas chronic increases in estrogen downregulate serotonin receptors and increase the risk of depression and anxiety.69 Estrogens exert an agonistic effect on serotonergic activity by increasing the number of serotonergic receptors and by increasing the transport and uptake of serotonin. Estrogens also increase synthesis of serotonin, upregulate serotonin receptors, downregulate serotonin receptors, and decrease the activity of an enzyme (monoamine oxidase) involved in serotonin metabolism.70 The cumulative effect of estrogen on the serotonin system is thus to enhance serotonergic activity.

Estrogens appear to also increase noradrenergic activity by increasing receptor turnover, decreasing noradrenergic reuptake, and decreasing both the number and the sensitivity of dopamine-2 receptors.71 Animal studies suggest that there are potent behavioral effects associated with estrogen withdrawal or fluctuations in estrogen; bilateral ovariectomy of mice increases the duration of immobility—which is often taken as a measure of behavioral depression—while estrogen replacement decreases depressive-like behavior.72

 

The Transition Triad: A Biopsychosocial Model of Depression

Women experience depression during the menopausal transition because of a wide range of factors. It is only by understanding biologic, psychiatric, and social risk factors that we can begin to evaluate depression in midlife women.

The morbidity associated with mood disorders during midlife may be quite significant; as life expectancy continues to increase, it will become increasingly important to prevent, recognize, and treat depression during the menopausal transition in order to reduce the possibility of long-term sequelae.31 Women report symptoms of physical illness at higher rates, visit physicians more often, and make greater use of healthcare services than do men.54 This gives PCPs the opportunity to intervene in the lives of women who may not realize that they have a treatable problem. Awareness of the biopsychosocial factors that can impact depression during the menopausal transition may assist clinicians in the challenge of distinguishing symptoms of MDD from menopausal symptoms, and may help in the diagnosis and treatment of women with new-onset depression.

 

Evaluating Depression During the Menopausal Transition

Recognizing depression in the context of the menopausal transition can be challenging. First, there is considerable overlap between menopause-related symptoms and symptoms of MDD, including diminished energy level, poor concentration, sleep disturbance, weight change, and decreased libido (Figure 2).59,73 In addition, it may be difficult to differentiate whether mood symptoms are simply reactions to the myriad life stressors that can affect midlife women or are indicative of a psychiatric diagnosis.

 

 

Screening for depression in primary care can be done relatively quickly and easily by asking just two questions: “During the past month, have you often been bothered by feeling down, depressed, or hopeless?” and “During the past month, have you been bothered by little interest or pleasure in doing things?”74 When 421 patients were given a psychiatric interview and a screening questionnaire comprised of 27 items, these two questions were clinically most useful, offering 97% sensitivity and 67% specificity for a diagnosis of clinical depression.73 If these questions are answered in the affirmative, a more thorough evaluation for depression is needed. Although the study sample included women and men of all ages and this was not a menopause-specific study, this screening tool for depression, used in conjunction with a clinical interview (which should include an assessment of reproductive status and history, current menopausal status, a review of changes in menstrual pattern, and a history of reproductive-related mood disturbance) and an evaluation of the presence and severity of somatic symptoms (which should include vasomotor symptoms, sleep disturbances, and changes in sexual function) provides an efficient and effective means of identifying depression during the menopausal transition in clinical practice.

 

Treating Depression During the Menopausal Transition

Management of depression during the menopausal transition should be part of a comprehensive treatment strategy designed to address the needs of the patient as a whole. As with depression at other times in a woman’s life, antidepressant therapy may be indicated. When selecting a therapy, it is important to consider whether treatment outcomes are affected by factors such as age, sex, and menopausal status.

As discussed previously, the neuroendocrine effects of estrogen are mediated at least in part by serotonergic activity in the brain.71,75 This mechanism could suggest that one therapeutic approach to menopausal depression would be to use antidepressants that modulate serotonin at the synapse.14 Alternatively, if estrogen serves to augment the serotonin system, it is possible that loss of this effect could result in a dampening of the efficacy of purely serotonergic agents in postmenopausal women compared with their use in premenopausal women.44 Unfortunately, relatively few studies have tested these hypotheses in a clinical setting. Of those that have evaluated the effect of gender and/or menopausal status on outcomes76-85 the evidence has not been entirely consistent, though differences could be attributable to small sample sizes and lack of statistical power to detect such interactions in some studies rather than discrepant findings.

In general, several studies have shown that compared with men, women may respond differently to some antidepressants,77,79,81,82 and postmenopausal women may respond differently than premenopausal women.76-83 For example, when the efficacy of sertraline, a selective serotonin reuptake inhibitor (SSRI), was compared to imipramine, a tricyclic antidepressant (TCA), gender- and menopause-related differences in response rates were found. Women were significantly more likely to show a favorable response to the SSRI, whereas men were more likely to benefit from the TCA; among the women, the difference between the two agents was found only in premenopausal women.82 More recently, a study in primary care patients found that menopause negatively affected response to SSRIs in depressed women.79 Specifically, the likelihood of responding to SSRIs was two times greater in premenopausal women compared with postmenopausal women. Other studies evaluating age as a proxy for menopausal status have found that antidepressant response in younger and older women differs, with younger women generally more treatment-responsive to SSRIs.76,80,83 Martenyi and colleagues81 reported that women in their reproductive years (defined in this study as <44 years of age) tended to be more responsive to SSRI treatment than to the predominantly noradrenergic tetracyclic antidepressant maprotiline. A meta-analysis of eight double-blind clinical trials of 2,045 patients randomized to treatment with the serotonin norepinephrine reuptake inhibitor (SNRI) venlafaxine, SSRIs, or placebo76 found poorer response in the older women compared with the younger women taking SSRIs, with no such difference observed among women taking the SNRI. However, older women taking SSRIs and concomitant hormone therapy had a comparable response to younger women taking SSRIs alone.76

These results are controversial, as some studies have failed to replicate the finding of gender and/or menopausal status differences in antidepressant response.78,80,84 For example, a re-analysis of data from two clinical studies found no evidence that women have a preferential response to SSRIs or that men have a better TCA response.80 Another analysis of data from nine clinical trials found that women and men in all age groups had comparable response rates to TCAs and to the SSRI fluoxetine, although older women did show a superior response to TCAs compared with younger women.78 Finally, a post-hoc analysis of a study in 184 depressed women treated with fluoxetine failed to find a significant difference in response or remission rates among the pre-, peri-, and postmenopausal groups.84 Postmenopausal women did have significantly more residual symptoms following acute-phase treatment, though this difference was no longer significant when adjusted for baseline severity. It is important to note that the lack of statistical differences in this study might have been a function of the small sample sizes in the peri- (N=28) and postmenopausal (N=35) groups and hence low statistical power to detect differences in outcomes.84

It also remains unclear if the potentially diminished antidepressant efficacy in older or postmenopausal women is limited to SSRIs. Available studies suggest that the response to SNRI treatment is comparable in older and younger women.76,85 Prospective studies designed to specifically address the issue of a treatment-by-menopausal-status interaction are warranted to confirm the preliminary data described above.

 

Use of Estrogen in Treatment of Menopausal Depression

Hormone therapy has been used for many years to treat menopausal symptoms, and in more recent years tested as an option for peri- and postmenopausal mood disturbance.16,44,48,59,86 The value of hormone therapy as augmentation for antidepressant response has been evaluated in a handful of studies, with mixed results. In a double-blind study of fluoxetine in elderly depressed patients,87 fluoxetine treatment was significantly more effective than placebo in women who were taking concomitant estrogen therapy but not among those women who were not taking estrogen. A similar analysis in a study of sertraline demonstrated that older depressed women (>60 years of age) taking estrogen had significantly greater global improvement and quality of life than those not receiving estrogen.88 In contrast to these results, a reanalysis of data from a relapse prevention study found similar efficacy in fluoxetine-treated women ≥45 years of age with and without estrogen therapy.89 Finally, a small recently published pilot trial in postmenopausal women found that hormone therapy did not alter the response rate to treatment with sertraline, though hormone therapy may accelerate the treatment effect.90

The efficacy of estrogen as a monotherapy for depression also has been assessed in peri- and postmenopausal women. Preliminary data by Schmidt and colleagues86 suggested a role for estradiol in a double-blind, placebo-controlled, randomized clinical trial of 34 perimenopausal women with predominantly minor depression. These preliminary findings have since been replicated in a somewhat larger group of perimenopausal women91 with MDD, dysthymic disorder, or minor depressive disorder randomized to treatment with transdermal estradiol or placebo. Results were consistent regardless of DSM-IV diagnosis. However, evidence does not support the efficacy of estrogen as monotherapy for postmenopausal depression. In a randomized controlled trial of mild-to-moderate depression in postmenopausal women92 there was no difference between estrogen and placebo after 8 weeks of treatment. The authors concluded that estradiol cannot be considered effective treatment for postmenopausal depression.92

In summary, available evidence suggests a possible role for hormone therapy as monotherapy in perimenopausal women. The use of hormone therapy as an augmenting agent for antidepressant therapy is interesting but remains to be demonstrated prospectively in a randomized controlled trial. A careful consideration of the risks and benefits of these options should be made in conjunction with the patient, particularly in light of the widely publicized potential risks associated with hormone therapy for some patients.93 Although hormone therapy has been the mainstay of treatment for menopausal symptoms for many years, women are now increasingly likely to treat menopausal symptoms with nonhormonal treatments (eg, antidepressants; gabapentin; and alternative therapies, including exercise, herbal products, dietary supplements, and mind-body techniques).94 As such, there may be similar reluctance among some patients to consider estrogen as a therapeutic option for depression. Recently published data from the Women’s Health Initiative trial suggest there is a differential risk-benefit profile depending on years since menopause.95,96 These data should be taken into consideration when assessing options for short-term treatment during the menopausal transition.97  

 

Conclusion

Although we now have a clearer understanding of the risk for depression during the menopausal transition, many unanswered questions remain regarding the approach to treatment in peri- and postmenopausal women. Whether estrogen can be prescribed safely for a brief period of time at the menopausal transition warrants continued study. Some of the larger, prospective clinical trials of antidepressants such as fluoxetine, sertraline, venlafaxine, and duloxetine should be replicated with a larger sample size before recommendations for one treatment class over another can be made with confidence. We must also continue to search for antidepressants that work by different mechanisms, which may prove more effective for perimenopausal women. Finally, management of depression during the menopausal transition should be part of a comprehensive treatment strategy that addresses the needs of the patient as a whole. PP

 

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93. Rossouw JE, Anderson GL, Prentice RL et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
94. Ma J, Drieling R, Stafford RS. US women desire greater professional guidance on hormone and alternative therapies for menopause symptom management. Menopause. 2006;13(3):506-516.
95. Manson JE, Allison MA, Rossouw JE et al. Estrogen therapy and coronary-artery calcification. N Engl J Med. 2007;356(25):2591-2602.
96. Rossouw JE, Prentice RL, Manson JE et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297(13):1465-1477.
97. Burger HG. WHI risks: any relevance to menopause management? Maturitas. 2007;57(1):6-10.

 

Latest Clinical Trial Data On Disease-Modifying Therapies from the 2008 International Conference on Alzheimer’s Disease

Clinical trial results examining a diversity of promising Alzheimer’s disease therapies were presented at the 2008 Alzheimer’s Association International Conference on Alzheimer’s Disease in Chicago. The therapies presented targeted a wide variety of possible mechanisms of action and revealed both advancements and setbacks in the larger effort to develop disease-modifying treatments for Alzheimer’s disease.

Data from the Phase III trials of tarenflurbil, formerly considered one of the more promising potential treatments, were discouraging. Robert C. Green, MD, MPH, of Boston University School of Medicine, reported on the randomized, double-blind, placebo-controlled trials of tarenflurbil, a selective amyloid-lowering compound that was shown in non-clinical trials to modulate gamma secretase activity. Over 1,649 subjects with mild Alzheimer’s disease were given tarenflurbil 800 mg  BID or placebo BID for 18 months. Primary outcome measures were defined as standard measures of cognition on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and activities of daily living on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The results showed no difference between groups: both declined approximately 7 points on the ADAS-cog and 10 points the ADCS-ADL. While tarenflurbil was generally well tolerated, it showed slightly higher incidences of anemia, infections, and gastrointestinal ulcers than placebo.

“It is definitive that there is no efficacy,” said Dr. Green. Myriad Genetics has discontinued its development of tarenflurbil for Alzheimer’s disease.

Other therapeutic targets showed more promise. PBT2, a metal-protein-attenuating compound, is being explored by Prana Biotechnology for its effect on the toxicity of amyloid-β (Aβ) toxicity on the brain. PBT2 is thought to reduce the toxicity of Aβ by preventing the interaction of Aβ with copper and zinc. A Phase IIa trial of PBT2 was conducted to determine its safety and tolerability and to observe the preliminary efficacy of the compound on memory and thinking. In the randomized, double-blind, placebo-controlled 12-week trial, 29 subjects with mild Alzheimer’s disease received placebo, 20 received PBT2 50 mg/day, and 29 received PBT2 250 mg/day.

Jeffrey L. Cummings, MD, director of the Mary S. Easton Centre for Alzheimer’s Disease at the David Geffen School of Medicine at the University of California, Los Angeles, reported the findings: The 250 mg group showed statistically significant improvement in two of the four executive function tests after 12 weeks. No significant trends were observed on the safety of the compound, no serious adverse events were reported, and tolerability was comparable to placebo. The trial also examined the effect of the compound on Alzheimer’s disease biomarkers, and found that subjects receiving 250 mg of PBT2 produced statistically less cerebrospinal Ab protein than subjects on placebo. 

“There is great interest in finding a biomarker,” said Dr. Cummings. “I think we have shown that.”

Another promising therapy departed from the theory of an amyloid protein mechanism of action, instead targeting tau, the neurofibrillary protein “tangles” originally described by Alois Alzheimer. Claud Wischik, chairman of TauRX Therapeutics, Singapore, and professor of Mental Health at the University of Aberdeen in Scotland, presented Phase IIb data on a methylthioninium chloride (MTC), which had been previously shown to dissolve tau tangles in test tube studies.

A double-blind, randomized, placebo-controlled study of MCT was conducted in 321 subjects with mild or moderate Alzheimer’s disease, with results taken at 24 weeks and 84 weeks. Subjects received oral MTC 30 mg, 60 mg, or 100 mg TID, or placebo. (The 100 mg capsule shell later proved defective.) Primary outcome measures were effects on cognition as measured by the ADAS-cog at 24 weeks. Secondary outcome measures were the effects of MTC on molecular brain imaging at 25 weeks, safety and tolerability, and disease modifying potential at 50 and 84 weeks. At 24 weeks, MTC produced a 5.5-unit improvement on the ADAS-cog in subjects with moderate Alzheimer’s disease receiving 60 mg tid compared to controls. By 50 weeks, MTC subjects showed an 81% reduced rate of decline compared to controls, a 6.8-unit difference on the ADAS-cog. MTC subjects’ ADAS-cog scores at 84 weeks were not significantly different from their scores at baseline. Single photon emission computed tomography and positron emission tomography showed that subjects on 60 mg MTC experienced less regional cerebral blood flow decline than control subjects. This effect was greatest in regions of the brain with the most severe tau accumulation: the hippocampus and entorhinal cortex. Phase III studies of MTC are planned for 2009.

Funding for the Phase III clinical trial on tarenflurbil was provided by Myriad Genetics. Dr. Green received no personal funding from the company. Funding for the Phase IIa trial of PBT2 was provided by Prana Biotechnology. Funding for the Phase IIb trial on MTC was provided by TauRx Therapeutics. (July 29, 2008. Alzheimer’s Association’s International Conference on Alzheimer’s Disease.) –RZ

 

FDA Approves Methlyphenidate HCI for the Treatment of ADHD in Adults 18–65 Years of Age

The United States Food and Drug Administration announced it has approved methlyphenidate HCI (Concerta extended-release, Johnson & Johnson) tablets for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults 18–65 years of age.  The approved dose range is 18–72 mg/day, with a recommended starting dose of 18 or 36 mg/day. Methylphenidate is already indicated for use in children and adolescents with ADHD.

The approval is based on the results of clinical trials in adults 18–65 years of age. Two double-blind, placebo-controlled studies were conducted in 627 adults 18–65 years of age.  The first study was a multicenter, parallel-group trial comparing methlyphenidate 36–108 mg/day with placebo during 7 weeks of dose titration. The second trial was a 5-week multicenter, parallel-group fixed-dose study during which participants received methlyphenidate 18, 36, and 72 mg/day.

The former study demonstrated the treatment effectiveness based on the change to final study visit on the Adult ADHD Investigator Rating Scale. In the latter trial, all three doses of methlyphenidate were, according to results, significantly more effective than placebo in improving Conners’ Adult Scale total scores at double-blind endpoint in adult subjects with ADHD.

The most common adverse reaction (>5%) reported in children and adolescents is upper abdominal pain. The most common adverse reactions (>10%) reported in adults are dry mouth, nausea, decreased appetite, headache, and insomnia.

For more information, please consult the medication’s full prescribing information (http://www.concerta.net/concerta/pages/full.jsp). –JRR

 

Detection and Management of Dementia in General Practice

Depression occurs in approximately 57% of dementia patients, demonstrating a high comorbidity in the conditions. Guidelines from the Royal Australian College of General Practitioners (RACGP) suggest using paper and pencil cognitive evaluations to assess crucial items, such as the possibility of other diagnoses and pathology, for the detection and management of dementia. Dimity Pond, PhD, FRACGP, Dip SSc, MBBS, at the University of Newcastle in Australia, and colleagues, compared findings from both general practitioner audits and the General Practitioner Assessment of Cognition (GPCOG) with that of the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly (CAMCOG) in terms of dementia detection. They also compared geriatric depression scale (GDS) findings to the clinical perspective with respect to concomitant depression.

The researchers sent letters to approximately 160 general practitioners and 2,000 of their patients ≥75 years of age from four Australian cities (Adelaide, Melbourne, Newcastle, and Sydney). Responding practitioners were assigned to either the intervention group or the control group. Their task was to audit patients; identify whether they had “possible,” “probable,” “definite,” or no dementia; and note the methods to their investigation (ie, pathology, radiology, pencil and paper tests, specialist order tests, services, and identification of other diagnoses) for those who answered with any of the first three responses. After the general practitioner’s audit, a research nurse conducted a battery of cognitive assessments, including the CAMCOG and GDS. The GPCOG was administered to each patient by general practitioners trained in intervention.

The general practitioner’s data from the CAMCOG found that 27% of patients scored <81, meaning they suffer from dementia. The GDS characterized 9% of this dementia group as depressed but not cognitively impaired, indicating a different diagnosis of depression than that of the general practitioners. Further, the general practitioners identified three patients with concomitant dementia and depression, one of whom fit the CAMCOG definition for dementia. In actuality, however, none of the three individuals fit the criteria for depression.

These results indicate that general practitioners struggle to make accurate diagnoses between dementia and depression. In addition, that the researchers found obvious patterns of investigation following RACGP guidelines, with radiology and pathology assessments as the most commonly used, suggests a need for improvement in the detection and management of dementia in general practice.

To increase accurate depression and dementia detection rates, the researchers recommend an approach that both acknowledges the need to minimize unnecessary patient anxiety and facilitates the benefits of early diagnosis with complementary services (ie, mobilizing support services, support for families and caretakers). The combination of clinical judgment and appropriate methods of investigation should lead to optimal detection and improved differential diagnoses. Pond and colleagues are further exploring paper and pencil tests with respect to general practitioner’s diagnostic accuracy in cognitive impairment.

Funding for this research was provided by the Australian National Health and Medical Research Council and the Dementia Collaborative Research Center. (ICAD 2008; Poster P1-280). –ML

 

Anosognosia: Assessment Tools for Its Epidemiologic Study in Geriatric Populations with Dementia

Anosognosia, a common feature of dementia that is associated with increased behavioral disturbance and reduced treatment compliance, is difficult to assess in elderly populations with dementia. There are limited methods or clinical tools available for the assessment of anosognosia, but many existing methods may be too lengthy and otherwise difficult to apply to epidemiologic research.

Trevor Buckley, MA, at Utah State University in Logan, and colleagues, tested a 7-item “metacognition questionnaire.” Modified Mini-Mental State Exam (3MS) results were collected at baseline. At 3-year follow-up, the 3MS was administered again, and subjects and informed caregivers both completed the self-report questionnaire. Questionnaire results were compared with two external criteria: change in 3MS scores over the 3-year period, and informed caregiver report using the Informant Questionnaire of Cognitive Decline in the Elderly.

Six hundred eighty-seven adults comprised the study population, of which 157 were classified with dementia. The mean age of all subjects was approximately 82 years of age. Of those with dementia, 61.1% (n=99) were male, and 34.9% (n=53) were female. In subjects without dementia, metacognitive ratings of decline were in alignment with a decline in 3MS ratings (t=2.21, P=.027) and informant ratings (OR=4.0, 95% CI=1.16, 13.85, P=.029). In subjects with dementia, however, metacognitive ratings were inversely associated with a decline in 3MS ratings (t=-1.923, P=.056) but not with informant ratings (OR=1.8, 95% CI=.56, 5.83, P=.32).

As expected, the results indicate that self-perception of cognitive and functional decline in subjects with dementia are likely to run counter to the informed caregivers’ perceptions and to 3MS scores. In contrast, those without dementia reported much more accurate perceptions of their own cognitive and functional decline.

“These findings promote the use of a brief questionnaire of metcognition in conjunction with either informant report or cognitive test performance to assess anosognosia,” said JoAnn Tschanz, PhD, a co-author of the study. “The brevity of each of the measures is a particularly appealing feature that lends itself for use in clinical and research settings.”

Funding for this research was provided by the National Institute on Aging. (ICAD 2008; Poster P2-241). –LS

 

Cognitive Benefits of Hormone Therapy Use in Women Matched for Cardiovascular Risk Factors

According to data from the Women’s Health Initiative study and its Memory Study (WHIMS), there are increased rates of cardiovascular risk, cognitive decline, and dementia in women using hormone therapy during menopause. Further, prior research has reported cardiovascular and cognitive benefits and reduced risk for dementia with menopausal hormone therapy as a result of a “healthy-user” bias. This theory states that women choosing to use hormone therapy during menopausal transition are healthier than women who do not, and as a result, the healthier women experience hormone treatment advantages. However, Carey Gleason, PhD, at the University of Wisconsin in Madison, and colleagues, found that more current findings support both reduced risk of Alzheimer’s disease and beneficial neurobiologic and cognitive effects of menopausal hormonal therapy independent of health-related factors.

To investigate the “healthy-user” bias, the researchers sent questionnaires to 237 women who were part of the Midwest Initiative for Dementia Screening. The surveys assessed one’s health history, menopausal status, and hormone use. One-hundred ninety of 213 patients who responded were stratified into two groups of either users (previous or current; n=95) or non-users (n=95) and were matched for cardiovascular conditions, health-related behaviors, age, and education. Clinical screening involved a neuropsychological set of evaluations, including the Mini Mental State Examination, Cognistat, Trail Making Test A and B, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List, Animal Fluency, the Stroop Color Word Test, and the Geriatric Depression Scale to audit mood.

Participants’ scores were compared using a series of t-tests and adjusted using an overall α=.10 and a Sidak-Holm sequential formula. Results found that the between-group means were statistically different for Cognistat similarities, CERAD delayed recall, and CERAD retention. These findings imply that the “healthy-user” bias does not explain differences in cognitive performance between the two cohorts.

The researchers suggest that it is more likely that developing theories discussing time of hormonal therapy initiation as a factor conducive to neuropsychological benefits and reduced Alzheimer’s disease risk (eg, “critical period” theory) explain data discrepancies among previous research, WHIMS, and current research.

Funding for this research was provided by grants from the National Institute on Aging; the Extendicare Foundation; and the Geriatric Research, Education, and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. (ICAD 2008; Poster P2-393). –ML

 

Condensed Informational Counseling for Potential Genetic Alzheimer’s Disease Risk Effective Communication Tool for Patients

Researchers studying Alzheimer’s disease have identified apolipoprotein E (APOE) as a genetic factor that, if present in asymptomatic patients, may increase the risk of the later development of the neurodegenerative disease. Despite the potential effectiveness of APOE as a genetic marker for Alzheimer’s disease, researchers have cautioned its clinical use until further study is conducted into the impact of susceptibility genotyping and communicating such information to patients.

Currently, studies have shown that APOE genotype information can only be safely communicated to first-degree relatives of Alzheimer’s disease patients following traditional genetic counseling procedures. These procedures include in-person appointments between patients and genetic counselors, which can be time and resource consuming for genetic counselors. Recently, researchers investigated the use of a condensed genetic informational session, which may be more feasible for counselors, and its potential impact for patients. 

J. Scott Roberts, PhD, of the Department of Health Behavior and Health Education at the University of Michigan School of Public Health in Ann Arbor, and colleagues, studied the psychosocial and behavioral impact of condensed APOE genotype disclosure among 352 patients in The Risk Evaluation and Education for Alzheimer’s Disease study, a multi-center, randomized trial. Patients in the study were divided into two groups. one group (n=120) received the extended informational protocol, which included an in-person education session and counseling. The second group (n=232) received the condensed protocol, which included education brochures sent by mail and a question-and-answer session with a counselor. Study outcome measures included clinical cut-off rates on various screening tools, such as the Center for Epidemiologic Studies Depression Scale and the Beck Anxiety Inventory, among others. Patients received follow-up assessments at 6-week, 6-month, and 12-month intervals.

Both groups received neuropsychological and psychiatric screening, and all patients were asymptomatic adult children or siblings of patients with Alzheimer’s disease. Among all study patients, 280 continued to Alzheimer’s disease risk assessment with APOE disclosure (condensed protocol, n=187; extended protocol, n=93).

Roberts and colleagues found that there were few significant differences between the condensed and extended protocol groups in rates of depression or anxiety as well as in self-report health measures. Patients in the condensed protocol group reported higher levels of distress at the 6-week follow-up, however, that difference was not found at the 12-month follow-up. Patients in either group also changed their behavior at similar rates, with the percentage of patients in both groups making any health-related changes following APOE assessment being the same (54%).

In addition, more patients in the condensed protocol group reported understanding of genotype information (60% vs. 59%) and recall of lifetime risk of Alzheimer’s disease (61% vs. 51%) than those in the extended protocol group. The authors concluded that patients in the condensed genotype information protocol group had mean anxiety and depression levels far below cut-off measures and there were no differences in understanding among the two groups. As time demands for counselors in the condensed protocol group were significantly lower than demands for those in the extended protocol group (33 minutes vs. 76 minutes), the authors recommend that further research be conducted to explore the feasibility and effectiveness of alternative models for genetic counseling protocols for Alzheimer’s disease.

Funding for this research was provided by the National Institutes of Health. (ICAD 2008; Poster P2-282). –CP

 

Estrogen May Ease Schizophrenia in Women

According to the National Institute of Mental Health, schizophrenia affects approximately 1.1% of the population ≥18 years of age in any given year. It is usually diagnosed in late adolescence or early adulthood. According to a randomized, double-blind study by Jayashri Kulkarni, MD, of the Alfred and Monash University in Melbourne, Australia, and colleagues, estrogen may have therapeutic effects in women with severe mental illnesses, including schizophrenia.

With the goal of comparing the efficacy of adjunctive transdermal estradiol (a form of estrogen) with that of adjunctive placebo in the treatment of acute psychotic symptoms, female patients were recruited from inpatient acute hospital wards and outpatient clinics of two metropolitan Melbourne general hospitals. Participants included 102 schizophrenic women of childbearing age (73 of whom were outpatients) who were in an acute or chronic stage of their illness. Over the course of 28 days, patients were randomized to receive 100 microg of transdermal estradiol (n=56) or transdermal placebo (n=46). All patients continued to take their regular medications, which most commonly included atypical antipsychotics such as olanzapine. Using the Positive and Negative Syndrome Scale, psychopathalogic symptoms were assessed weekly. Results found that compared to women receiving antipsychotics alone, the addition of 100 microg of transdermal estradiol reduced positive (P<.05) and general psychopathalogic (P<.05) symptoms significantly.

Estrogen therapy may prove useful in schizophrenic women after childbirth and during menopause (when they are more prone to relapse) as well as during low-estrogen phases of a woman’s menstrual cycle. (Arch Gen Psychiatry. 2008;65(8):955-960). –DC

 

Family Meals May Increase Parental Communication and Decrease Substance Abuse for Teenage Girls

Studies have shown that meals between parents and adolescents provide an environment for communication as well as parental monitoring of mood or behavioral changes among adolescents and teenagers. Researchers in the Division of Adolescent Health and Medicine at the University of Minnesota in Minneapolis sought to examine if family meals with adolescents could deter later incidence of substance abuse.

Marla Eisenberg, ScD, MPH, and colleagues studied 806 adolescents (mean age=12.8 years) attending public schools between 1998–1999 to determine how often participants ate meals with parents and if family meals deterred later substance abuse. Adolescents were asked how often their families ate meals together in the past week as well as the presence or frequency of smoking and/or alcohol and marijuana use.

A second survey was conducted by mail 5 years later (2003–2004) which investigated the presence or frequency of family meals and substance abuse among teenagers. Among all participants, 45.4% were male and 54.6% were female, and the mean age at follow-up was 17.2 years.

According to the first survey, approximately 60% of adolescents ate >5 family meals each week, which was the expected result. Rates of family meals were lower for teenagers at the 5-year follow-up evaluation. Regarding substance abuse, the authors found significantly lower rates of smoking and marijuana or alcohol use among female participants who reported >5 family meals per week (approximately 50% lower rates of substance abuse when compared to female teenagers who reported <5 family meals per week). This finding was not significant for male participants.

The authors concluded that frequent family meals may provide increased parental/child communication, which may lead to lower rates of substance abuse. They also found that these lower abuse rates may not be significant for male teenagers due to societal expectations and differences in parental interaction with male children. (J Adolesc Health. 2008;43(2):151-156.) –CP

 

New Medications May Help Drinkers Battle Alcohol Dependence

Alcohol-dependent individuals suffer from destructive symptoms affecting their physicality, mentality, and interpersonal relationships. However, a study by Bankole A. Johnson, DSc, MD, PhD, MPhil, FRCPsych, and colleagues from the Medical University of South Carolina suggest that certain medications may help alcoholics moderate their alcohol consumption and prevent relapse.

Johnson and colleagues studied the effects of topiramate in 371 alcohol-dependent patients during a 14-week, double-blind, randomized controlled trial. While receiving weekly adherence-enhancement therapy, the participants were either given topiramate (≤300 mg/day) or placebo. The researchers compared the physical, mental, and psychosocial effects of topiramate to that of placebo and found that the former was more effective in reducing body mass index (mean difference, 1.08), liver enzyme levels (P<.01 for all), plasma cholesterol level (mean difference, 13.3 mg/dL), and systolic (mean difference, 9.7 mm Hg) and diastolic (mean difference, 6.74 mm Hg) blood pressure. Such reductions may lower risk of fatty liver degeneration, in turn, decreased risk of cirrhosis and cardiovascular disease.

Though the topiramate cohort reported more side effects (eg, paresthesia, taste perversion, anorexia, difficulty with concentration) than those in the placebo group, its members experienced significantly decreased psychological compulsion and improved psychosocial health and quality of life. These benefits reduce risk of relapse and long-term negative outcomes.

Research Society on Alcoholism president Raymond Anton, MD, disclosed results from the initial 6-week active treatment phase of a 14-week double-blind, placebo-controlled study involving 60 alcohol-dependent patients as characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, who took part in the Prometa Protocol. Participant level of alcohol withdrawal was assessed via the 67-point Clinical Institute of Withdrawal Assessment (CIWA). Based on their CIWA scores, patients were placed in either the higher (scores ≥7; n=18) or lower (scores <7; n=42) alcohol withdrawal group. That the patients were not required to maintain alcohol abstinence prior to research should be noted.

Eight patients in the higher CIWA group and 25 patients in the lower CIWA group received the pharmacologic aspect (ie, a combination of generic medications) of the treatment program while the remaining members of each division received placebo. During the first 6 weeks of active treatment, all participants received standardized behavioral counseling sessions and were evaluated weekly for drinking, craving, mood, sleep, and adverse effects from treatment.

Patients reported reduced cravings and alcohol withdrawal symptoms, more consistent abstinence, and improved mood and sleep. However, the full 14-week study is still underway, as the results represent patient response during the first 6 weeks of active treatment. (Arch Intern Med. 2008;168(11):1188-1199) –ML

 

Sildenafil Effective in the Treatment of Antidepressant-related Female Sexual Dysfunction

Women taking antidepressants may experience treatment-related sexual dysfunction, often causing them to prematurely discontinue treatment. Sexual dysfunction is particularly associated with  the most commonly prescribed antidepressants for outpatients 18–65 years of age, selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressant-associated sexual dysfunction occurs in an estimated 30% to 70% of men and women treated for major depressive disorder (MDD) with first- or second-generation agents. There is a three-fold increased risk of nonadherence that leads to increased relapse and recurrence.

A study of sildenafil by H. George Nurnberg, MD, of the University of New Mexico School of Medicine in Albuquerque, and colleagues, proved promising for the reduction in adverse sexual effects of SSRIs in women. In an 8-week, prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 2003 and January 2007 at seven United States research centers, sildenafil was compared to placebo in 98 women (mean age=approximatetly 37 years) with in-remission MDD. Participants were randomly assigned to sildenafil (n=49) at a flexible dose starting at 50 mg and adjustable to 100 mg, approximately 1–2 hours before sexual activity, or placebo (n=49). Seventy-three percent of women taking placebo, compared to 28% taking sildenafil, reported no improvement with treatment. Scales used in the study included the Clinical Gloabal Impression sexual function scale, the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale–female version, the University of New Mexico Sexual Function Inventory–female version, a sexual activity event log, and the Hamilton Rating Scale for Depression. Women in the sildenafil group showed greater improvement in sexual function compared to women in the placebo group. Adverse effects included headache, flushing, and dyspepsia, but none of the patients withdrew due to serious adverse events.

The study established that selective phosphodiesterase type 5 inhibitors, such as sildanefil, are effective for women for the treatment of antidepressant-related sexual dysfunction. Thus, patients being treated for depression can continue with antidepressant treatment without the worry of adverse sexual effects. (JAMA. 2008;300(4):395-404). –DC

Posters were drawn from the Annual Meeting of the Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD; July 26-31, 2008, Chicago, Illinois). Psychiatric dispatches is written by Dena Croog, Michelisa Lanche, Carlos Perkins, Jr,, José R. Ralat, Lonnie Stoltzfoos, and Rebecca Zerzan.

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Latest Clinical Trial Data On Disease-Modifying Therapies from the 2008 International Conference on Alzheimer’s Disease

Clinical trial results examining a diversity of promising Alzheimer’s disease therapies were presented at the 2008 Alzheimer’s Association International Conference on Alzheimer’s Disease in Chicago. The therapies presented targeted a wide variety of possible mechanisms of action and revealed both advancements and setbacks in the larger effort to develop disease-modifying treatments for Alzheimer’s disease.

Data from the Phase III trials of tarenflurbil, formerly considered one of the more promising potential treatments, were discouraging. Robert C. Green, MD, MPH, of Boston University School of Medicine, reported on the randomized, double-blind, placebo-controlled trials of tarenflurbil, a selective amyloid-lowering compound that was shown in non-clinical trials to modulate gamma secretase activity. Over 1,649 subjects with mild Alzheimer’s disease were given tarenflurbil 800 mg  BID or placebo BID for 18 months. Primary outcome measures were defined as standard measures of cognition on the Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) and activities of daily living on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale. The results showed no difference between groups: both declined approximately 7 points on the ADAS-cog and 10 points the ADCS-ADL. While tarenflurbil was generally well tolerated, it showed slightly higher incidences of anemia, infections, and gastrointestinal ulcers than placebo.

“It is definitive that there is no efficacy,” said Dr. Green. Myriad Genetics has discontinued its development of tarenflurbil for Alzheimer’s disease.

Other therapeutic targets showed more promise. PBT2, a metal-protein-attenuating compound, is being explored by Prana Biotechnology for its effect on the toxicity of amyloid-β (Aβ) toxicity on the brain. PBT2 is thought to reduce the toxicity of Aβ by preventing the interaction of Aβ with copper and zinc. A Phase IIa trial of PBT2 was conducted to determine its safety and tolerability and to observe the preliminary efficacy of the compound on memory and thinking. In the randomized, double-blind, placebo-controlled 12-week trial, 29 subjects with mild Alzheimer’s disease received placebo, 20 received PBT2 50 mg/day, and 29 received PBT2 250 mg/day.

Jeffrey L. Cummings, MD, director of the Mary S. Easton Centre for Alzheimer’s Disease at the David Geffen School of Medicine at the University of California, Los Angeles, reported the findings: The 250 mg group showed statistically significant improvement in two of the four executive function tests after 12 weeks. No significant trends were observed on the safety of the compound, no serious adverse events were reported, and tolerability was comparable to placebo. The trial also examined the effect of the compound on Alzheimer’s disease biomarkers, and found that subjects receiving 250 mg of PBT2 produced statistically less cerebrospinal Ab protein than subjects on placebo. 

“There is great interest in finding a biomarker,” said Dr. Cummings. “I think we have shown that.”

Another promising therapy departed from the theory of an amyloid protein mechanism of action, instead targeting tau, the neurofibrillary protein “tangles” originally described by Alois Alzheimer. Claud Wischik, chairman of TauRX Therapeutics, Singapore, and professor of Mental Health at the University of Aberdeen in Scotland, presented Phase IIb data on a methylthioninium chloride (MTC), which had been previously shown to dissolve tau tangles in test tube studies.

A double-blind, randomized, placebo-controlled study of MCT was conducted in 321 subjects with mild or moderate Alzheimer’s disease, with results taken at 24 weeks and 84 weeks. Subjects received oral MTC 30 mg, 60 mg, or 100 mg TID, or placebo. (The 100 mg capsule shell later proved defective.) Primary outcome measures were effects on cognition as measured by the ADAS-cog at 24 weeks. Secondary outcome measures were the effects of MTC on molecular brain imaging at 25 weeks, safety and tolerability, and disease modifying potential at 50 and 84 weeks. At 24 weeks, MTC produced a 5.5-unit improvement on the ADAS-cog in subjects with moderate Alzheimer’s disease receiving 60 mg tid compared to controls. By 50 weeks, MTC subjects showed an 81% reduced rate of decline compared to controls, a 6.8-unit difference on the ADAS-cog. MTC subjects’ ADAS-cog scores at 84 weeks were not significantly different from their scores at baseline. Single photon emission computed tomography and positron emission tomography showed that subjects on 60 mg MTC experienced less regional cerebral blood flow decline than control subjects. This effect was greatest in regions of the brain with the most severe tau accumulation: the hippocampus and entorhinal cortex. Phase III studies of MTC are planned for 2009.

Funding for the Phase III clinical trial on tarenflurbil was provided by Myriad Genetics. Dr. Green received no personal funding from the company. Funding for the Phase IIa trial of PBT2 was provided by Prana Biotechnology. Funding for the Phase IIb trial on MTC was provided by TauRx Therapeutics. (July 29, 2008. Alzheimer’s Association’s International Conference on Alzheimer’s Disease.) –RZ

 

FDA Approves Methlyphenidate HCI for the Treatment of ADHD in Adults 18–65 Years of Age

The United States Food and Drug Administration announced it has approved methlyphenidate HCI (Concerta extended-release, Johnson & Johnson) tablets for the treatment of attention-deficit/hyperactivity disorder (ADHD) in adults 18–65 years of age.  The approved dose range is 18–72 mg/day, with a recommended starting dose of 18 or 36 mg/day. Methylphenidate is already indicated for use in children and adolescents with ADHD.

The approval is based on the results of clinical trials in adults 18–65 years of age. Two double-blind, placebo-controlled studies were conducted in 627 adults 18–65 years of age.  The first study was a multicenter, parallel-group trial comparing methlyphenidate 36–108 mg/day with placebo during 7 weeks of dose titration. The second trial was a 5-week multicenter, parallel-group fixed-dose study during which participants received methlyphenidate 18, 36, and 72 mg/day.

The former study demonstrated the treatment effectiveness based on the change to final study visit on the Adult ADHD Investigator Rating Scale. In the latter trial, all three doses of methlyphenidate were, according to results, significantly more effective than placebo in improving Conners’ Adult Scale total scores at double-blind endpoint in adult subjects with ADHD.

The most common adverse reaction (>5%) reported in children and adolescents is upper abdominal pain. The most common adverse reactions (>10%) reported in adults are dry mouth, nausea, decreased appetite, headache, and insomnia.

For more information, please consult the medication’s full prescribing information (http://www.concerta.net/concerta/pages/full.jsp). –JRR

 

Detection and Management of Dementia in General Practice

Depression occurs in approximately 57% of dementia patients, demonstrating a high comorbidity in the conditions. Guidelines from the Royal Australian College of General Practitioners (RACGP) suggest using paper and pencil cognitive evaluations to assess crucial items, such as the possibility of other diagnoses and pathology, for the detection and management of dementia. Dimity Pond, PhD, FRACGP, Dip SSc, MBBS, at the University of Newcastle in Australia, and colleagues, compared findings from both general practitioner audits and the General Practitioner Assessment of Cognition (GPCOG) with that of the cognitive and self-contained part of the Cambridge Examination for Mental Disorders of the Elderly (CAMCOG) in terms of dementia detection. They also compared geriatric depression scale (GDS) findings to the clinical perspective with respect to concomitant depression.

The researchers sent letters to approximately 160 general practitioners and 2,000 of their patients ≥75 years of age from four Australian cities (Adelaide, Melbourne, Newcastle, and Sydney). Responding practitioners were assigned to either the intervention group or the control group. Their task was to audit patients; identify whether they had “possible,” “probable,” “definite,” or no dementia; and note the methods to their investigation (ie, pathology, radiology, pencil and paper tests, specialist order tests, services, and identification of other diagnoses) for those who answered with any of the first three responses. After the general practitioner’s audit, a research nurse conducted a battery of cognitive assessments, including the CAMCOG and GDS. The GPCOG was administered to each patient by general practitioners trained in intervention.

The general practitioner’s data from the CAMCOG found that 27% of patients scored <81, meaning they suffer from dementia. The GDS characterized 9% of this dementia group as depressed but not cognitively impaired, indicating a different diagnosis of depression than that of the general practitioners. Further, the general practitioners identified three patients with concomitant dementia and depression, one of whom fit the CAMCOG definition for dementia. In actuality, however, none of the three individuals fit the criteria for depression.

These results indicate that general practitioners struggle to make accurate diagnoses between dementia and depression. In addition, that the researchers found obvious patterns of investigation following RACGP guidelines, with radiology and pathology assessments as the most commonly used, suggests a need for improvement in the detection and management of dementia in general practice.

To increase accurate depression and dementia detection rates, the researchers recommend an approach that both acknowledges the need to minimize unnecessary patient anxiety and facilitates the benefits of early diagnosis with complementary services (ie, mobilizing support services, support for families and caretakers). The combination of clinical judgment and appropriate methods of investigation should lead to optimal detection and improved differential diagnoses. Pond and colleagues are further exploring paper and pencil tests with respect to general practitioner’s diagnostic accuracy in cognitive impairment.

Funding for this research was provided by the Australian National Health and Medical Research Council and the Dementia Collaborative Research Center. (ICAD 2008; Poster P1-280). –ML

 

Anosognosia: Assessment Tools for Its Epidemiologic Study in Geriatric Populations with Dementia

Anosognosia, a common feature of dementia that is associated with increased behavioral disturbance and reduced treatment compliance, is difficult to assess in elderly populations with dementia. There are limited methods or clinical tools available for the assessment of anosognosia, but many existing methods may be too lengthy and otherwise difficult to apply to epidemiologic research.

Trevor Buckley, MA, at Utah State University in Logan, and colleagues, tested a 7-item “metacognition questionnaire.” Modified Mini-Mental State Exam (3MS) results were collected at baseline. At 3-year follow-up, the 3MS was administered again, and subjects and informed caregivers both completed the self-report questionnaire. Questionnaire results were compared with two external criteria: change in 3MS scores over the 3-year period, and informed caregiver report using the Informant Questionnaire of Cognitive Decline in the Elderly.

Six hundred eighty-seven adults comprised the study population, of which 157 were classified with dementia. The mean age of all subjects was approximately 82 years of age. Of those with dementia, 61.1% (n=99) were male, and 34.9% (n=53) were female. In subjects without dementia, metacognitive ratings of decline were in alignment with a decline in 3MS ratings (t=2.21, P=.027) and informant ratings (OR=4.0, 95% CI=1.16, 13.85, P=.029). In subjects with dementia, however, metacognitive ratings were inversely associated with a decline in 3MS ratings (t=-1.923, P=.056) but not with informant ratings (OR=1.8, 95% CI=.56, 5.83, P=.32).

As expected, the results indicate that self-perception of cognitive and functional decline in subjects with dementia are likely to run counter to the informed caregivers’ perceptions and to 3MS scores. In contrast, those without dementia reported much more accurate perceptions of their own cognitive and functional decline.

“These findings promote the use of a brief questionnaire of metcognition in conjunction with either informant report or cognitive test performance to assess anosognosia,” said JoAnn Tschanz, PhD, a co-author of the study. “The brevity of each of the measures is a particularly appealing feature that lends itself for use in clinical and research settings.”

Funding for this research was provided by the National Institute on Aging. (ICAD 2008; Poster P2-241). –LS

 

Cognitive Benefits of Hormone Therapy Use in Women Matched for Cardiovascular Risk Factors

According to data from the Women’s Health Initiative study and its Memory Study (WHIMS), there are increased rates of cardiovascular risk, cognitive decline, and dementia in women using hormone therapy during menopause. Further, prior research has reported cardiovascular and cognitive benefits and reduced risk for dementia with menopausal hormone therapy as a result of a “healthy-user” bias. This theory states that women choosing to use hormone therapy during menopausal transition are healthier than women who do not, and as a result, the healthier women experience hormone treatment advantages. However, Carey Gleason, PhD, at the University of Wisconsin in Madison, and colleagues, found that more current findings support both reduced risk of Alzheimer’s disease and beneficial neurobiologic and cognitive effects of menopausal hormonal therapy independent of health-related factors.

To investigate the “healthy-user” bias, the researchers sent questionnaires to 237 women who were part of the Midwest Initiative for Dementia Screening. The surveys assessed one’s health history, menopausal status, and hormone use. One-hundred ninety of 213 patients who responded were stratified into two groups of either users (previous or current; n=95) or non-users (n=95) and were matched for cardiovascular conditions, health-related behaviors, age, and education. Clinical screening involved a neuropsychological set of evaluations, including the Mini Mental State Examination, Cognistat, Trail Making Test A and B, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Word List, Animal Fluency, the Stroop Color Word Test, and the Geriatric Depression Scale to audit mood.

Participants’ scores were compared using a series of t-tests and adjusted using an overall α=.10 and a Sidak-Holm sequential formula. Results found that the between-group means were statistically different for Cognistat similarities, CERAD delayed recall, and CERAD retention. These findings imply that the “healthy-user” bias does not explain differences in cognitive performance between the two cohorts.

The researchers suggest that it is more likely that developing theories discussing time of hormonal therapy initiation as a factor conducive to neuropsychological benefits and reduced Alzheimer’s disease risk (eg, “critical period” theory) explain data discrepancies among previous research, WHIMS, and current research.

Funding for this research was provided by grants from the National Institute on Aging; the Extendicare Foundation; and the Geriatric Research, Education, and Clinical Center of the William S. Middleton Memorial Veterans Hospital in Madison, Wisconsin. (ICAD 2008; Poster P2-393). –ML

 

Condensed Informational Counseling for Potential Genetic Alzheimer’s Disease Risk Effective Communication Tool for Patients

Researchers studying Alzheimer’s disease have identified apolipoprotein E (APOE) as a genetic factor that, if present in asymptomatic patients, may increase the risk of the later development of the neurodegenerative disease. Despite the potential effectiveness of APOE as a genetic marker for Alzheimer’s disease, researchers have cautioned its clinical use until further study is conducted into the impact of susceptibility genotyping and communicating such information to patients.

Currently, studies have shown that APOE genotype information can only be safely communicated to first-degree relatives of Alzheimer’s disease patients following traditional genetic counseling procedures. These procedures include in-person appointments between patients and genetic counselors, which can be time and resource consuming for genetic counselors. Recently, researchers investigated the use of a condensed genetic informational session, which may be more feasible for counselors, and its potential impact for patients. 

J. Scott Roberts, PhD, of the Department of Health Behavior and Health Education at the University of Michigan School of Public Health in Ann Arbor, and colleagues, studied the psychosocial and behavioral impact of condensed APOE genotype disclosure among 352 patients in The Risk Evaluation and Education for Alzheimer’s Disease study, a multi-center, randomized trial. Patients in the study were divided into two groups. one group (n=120) received the extended informational protocol, which included an in-person education session and counseling. The second group (n=232) received the condensed protocol, which included education brochures sent by mail and a question-and-answer session with a counselor. Study outcome measures included clinical cut-off rates on various screening tools, such as the Center for Epidemiologic Studies Depression Scale and the Beck Anxiety Inventory, among others. Patients received follow-up assessments at 6-week, 6-month, and 12-month intervals.

Both groups received neuropsychological and psychiatric screening, and all patients were asymptomatic adult children or siblings of patients with Alzheimer’s disease. Among all study patients, 280 continued to Alzheimer’s disease risk assessment with APOE disclosure (condensed protocol, n=187; extended protocol, n=93).

Roberts and colleagues found that there were few significant differences between the condensed and extended protocol groups in rates of depression or anxiety as well as in self-report health measures. Patients in the condensed protocol group reported higher levels of distress at the 6-week follow-up, however, that difference was not found at the 12-month follow-up. Patients in either group also changed their behavior at similar rates, with the percentage of patients in both groups making any health-related changes following APOE assessment being the same (54%).

In addition, more patients in the condensed protocol group reported understanding of genotype information (60% vs. 59%) and recall of lifetime risk of Alzheimer’s disease (61% vs. 51%) than those in the extended protocol group. The authors concluded that patients in the condensed genotype information protocol group had mean anxiety and depression levels far below cut-off measures and there were no differences in understanding among the two groups. As time demands for counselors in the condensed protocol group were significantly lower than demands for those in the extended protocol group (33 minutes vs. 76 minutes), the authors recommend that further research be conducted to explore the feasibility and effectiveness of alternative models for genetic counseling protocols for Alzheimer’s disease.

Funding for this research was provided by the National Institutes of Health. (ICAD 2008; Poster P2-282). –CP

 

Estrogen May Ease Schizophrenia in Women

According to the National Institute of Mental Health, schizophrenia affects approximately 1.1% of the population ≥18 years of age in any given year. It is usually diagnosed in late adolescence or early adulthood. According to a randomized, double-blind study by Jayashri Kulkarni, MD, of the Alfred and Monash University in Melbourne, Australia, and colleagues, estrogen may have therapeutic effects in women with severe mental illnesses, including schizophrenia.

With the goal of comparing the efficacy of adjunctive transdermal estradiol (a form of estrogen) with that of adjunctive placebo in the treatment of acute psychotic symptoms, female patients were recruited from inpatient acute hospital wards and outpatient clinics of two metropolitan Melbourne general hospitals. Participants included 102 schizophrenic women of childbearing age (73 of whom were outpatients) who were in an acute or chronic stage of their illness. Over the course of 28 days, patients were randomized to receive 100 microg of transdermal estradiol (n=56) or transdermal placebo (n=46). All patients continued to take their regular medications, which most commonly included atypical antipsychotics such as olanzapine. Using the Positive and Negative Syndrome Scale, psychopathalogic symptoms were assessed weekly. Results found that compared to women receiving antipsychotics alone, the addition of 100 microg of transdermal estradiol reduced positive (P<.05) and general psychopathalogic (P<.05) symptoms significantly.

Estrogen therapy may prove useful in schizophrenic women after childbirth and during menopause (when they are more prone to relapse) as well as during low-estrogen phases of a woman’s menstrual cycle. (Arch Gen Psychiatry. 2008;65(8):955-960). –DC

 

Family Meals May Increase Parental Communication and Decrease Substance Abuse for Teenage Girls

Studies have shown that meals between parents and adolescents provide an environment for communication as well as parental monitoring of mood or behavioral changes among adolescents and teenagers. Researchers in the Division of Adolescent Health and Medicine at the University of Minnesota in Minneapolis sought to examine if family meals with adolescents could deter later incidence of substance abuse.

Marla Eisenberg, ScD, MPH, and colleagues studied 806 adolescents (mean age=12.8 years) attending public schools between 1998–1999 to determine how often participants ate meals with parents and if family meals deterred later substance abuse. Adolescents were asked how often their families ate meals together in the past week as well as the presence or frequency of smoking and/or alcohol and marijuana use.

A second survey was conducted by mail 5 years later (2003–2004) which investigated the presence or frequency of family meals and substance abuse among teenagers. Among all participants, 45.4% were male and 54.6% were female, and the mean age at follow-up was 17.2 years.

According to the first survey, approximately 60% of adolescents ate >5 family meals each week, which was the expected result. Rates of family meals were lower for teenagers at the 5-year follow-up evaluation. Regarding substance abuse, the authors found significantly lower rates of smoking and marijuana or alcohol use among female participants who reported >5 family meals per week (approximately 50% lower rates of substance abuse when compared to female teenagers who reported <5 family meals per week). This finding was not significant for male participants.

The authors concluded that frequent family meals may provide increased parental/child communication, which may lead to lower rates of substance abuse. They also found that these lower abuse rates may not be significant for male teenagers due to societal expectations and differences in parental interaction with male children. (J Adolesc Health. 2008;43(2):151-156.) –CP

 

New Medications May Help Drinkers Battle Alcohol Dependence

Alcohol-dependent individuals suffer from destructive symptoms affecting their physicality, mentality, and interpersonal relationships. However, a study by Bankole A. Johnson, DSc, MD, PhD, MPhil, FRCPsych, and colleagues from the Medical University of South Carolina suggest that certain medications may help alcoholics moderate their alcohol consumption and prevent relapse.

Johnson and colleagues studied the effects of topiramate in 371 alcohol-dependent patients during a 14-week, double-blind, randomized controlled trial. While receiving weekly adherence-enhancement therapy, the participants were either given topiramate (≤300 mg/day) or placebo. The researchers compared the physical, mental, and psychosocial effects of topiramate to that of placebo and found that the former was more effective in reducing body mass index (mean difference, 1.08), liver enzyme levels (P<.01 for all), plasma cholesterol level (mean difference, 13.3 mg/dL), and systolic (mean difference, 9.7 mm Hg) and diastolic (mean difference, 6.74 mm Hg) blood pressure. Such reductions may lower risk of fatty liver degeneration, in turn, decreased risk of cirrhosis and cardiovascular disease.

Though the topiramate cohort reported more side effects (eg, paresthesia, taste perversion, anorexia, difficulty with concentration) than those in the placebo group, its members experienced significantly decreased psychological compulsion and improved psychosocial health and quality of life. These benefits reduce risk of relapse and long-term negative outcomes.

Research Society on Alcoholism president Raymond Anton, MD, disclosed results from the initial 6-week active treatment phase of a 14-week double-blind, placebo-controlled study involving 60 alcohol-dependent patients as characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, who took part in the Prometa Protocol. Participant level of alcohol withdrawal was assessed via the 67-point Clinical Institute of Withdrawal Assessment (CIWA). Based on their CIWA scores, patients were placed in either the higher (scores ≥7; n=18) or lower (scores <7; n=42) alcohol withdrawal group. That the patients were not required to maintain alcohol abstinence prior to research should be noted.

Eight patients in the higher CIWA group and 25 patients in the lower CIWA group received the pharmacologic aspect (ie, a combination of generic medications) of the treatment program while the remaining members of each division received placebo. During the first 6 weeks of active treatment, all participants received standardized behavioral counseling sessions and were evaluated weekly for drinking, craving, mood, sleep, and adverse effects from treatment.

Patients reported reduced cravings and alcohol withdrawal symptoms, more consistent abstinence, and improved mood and sleep. However, the full 14-week study is still underway, as the results represent patient response during the first 6 weeks of active treatment. (Arch Intern Med. 2008;168(11):1188-1199) –ML

 

Sildenafil Effective in the Treatment of Antidepressant-related Female Sexual Dysfunction

Women taking antidepressants may experience treatment-related sexual dysfunction, often causing them to prematurely discontinue treatment. Sexual dysfunction is particularly associated with  the most commonly prescribed antidepressants for outpatients 18–65 years of age, selective serotonin reuptake inhibitors (SSRIs) and non-SSRIs. Antidepressant-associated sexual dysfunction occurs in an estimated 30% to 70% of men and women treated for major depressive disorder (MDD) with first- or second-generation agents. There is a three-fold increased risk of nonadherence that leads to increased relapse and recurrence.

A study of sildenafil by H. George Nurnberg, MD, of the University of New Mexico School of Medicine in Albuquerque, and colleagues, proved promising for the reduction in adverse sexual effects of SSRIs in women. In an 8-week, prospective, parallel-group, randomized, double-blind, placebo-controlled clinical trial conducted between September 2003 and January 2007 at seven United States research centers, sildenafil was compared to placebo in 98 women (mean age=approximatetly 37 years) with in-remission MDD. Participants were randomly assigned to sildenafil (n=49) at a flexible dose starting at 50 mg and adjustable to 100 mg, approximately 1–2 hours before sexual activity, or placebo (n=49). Seventy-three percent of women taking placebo, compared to 28% taking sildenafil, reported no improvement with treatment. Scales used in the study included the Clinical Gloabal Impression sexual function scale, the Female Sexual Function Questionnaire, the Arizona Sexual Experience scale–female version, the University of New Mexico Sexual Function Inventory–female version, a sexual activity event log, and the Hamilton Rating Scale for Depression. Women in the sildenafil group showed greater improvement in sexual function compared to women in the placebo group. Adverse effects included headache, flushing, and dyspepsia, but none of the patients withdrew due to serious adverse events.

The study established that selective phosphodiesterase type 5 inhibitors, such as sildanefil, are effective for women for the treatment of antidepressant-related sexual dysfunction. Thus, patients being treated for depression can continue with antidepressant treatment without the worry of adverse sexual effects. (JAMA. 2008;300(4):395-404). –DC

Posters were drawn from the Annual Meeting of the Alzheimer’s Association International Conference on Alzheimer’s Disease (ICAD; July 26-31, 2008, Chicago, Illinois). Psychiatric dispatches is written by Dena Croog, Michelisa Lanche, Carlos Perkins, Jr,, José R. Ralat, Lonnie Stoltzfoos, and Rebecca Zerzan.

 

Needs Assessment: Methods of pre-surgical psychological evaluation, post-operative psychological support, and common psychological issues are presented to mental health professionals following patients’ surgery. As the field of bariatric surgery grows rapidly, it is necessary to be familiar with these issues to provide adequate care.

Learning Objectives:
• Understand the various roles mental health professionals play in a multidisciplinary team of a surgical weight-loss program.
• List the objectives of a pre-surgical weight-loss evaluation.
• Recognize common psychological issues patients face at various stages after bariatric surgery.

Target Audience: Primary care physicians and psychiatrists.

CME Accreditation Statement: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation: The Mount Sinai School of Medicine designates this educational activity for a maximum of 3 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty Disclosure Policy Statement: It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the course material.

This activity has been peer-reviewed and approved by Eric Hollander, MD, chair and professor of psychiatry at the Mount Sinai School of Medicine, and Norman Sussman, MD, editor of Primary Psychiatry and professor of psychiatry at New York University School of Medicine. Review Date: June 23, 2008.

Drs. Hollander and Sussman report no affiliation with or financial interest in any organization that may pose a conflict of interest.

To receive credit for this activity: Read this article and the two CME-designated accompanying articles, reflect on the information presented, and then complete the CME posttest and evaluation. To obtain credits, you should score 70% or better. Early submission of this posttest is encouraged: please submit this posttest by August 1, 2010 to be eligible for credit. Release date: August 1, 2008. Termination date: August 31, 2010. The estimated time to complete all three articles and the posttest is 3 hours.

Primary Psychiatry. 2008;15(8):42-47

 

Dr. Huberman is clinical instructor in the Department of Psychiatry at New York University School of Medicine and in private practice in New York City.

Disclosure: Dr. Huberman reports no affiliation with or financial interest in any organization that may pose a conflict of interest.

Please direct all correspondence to: Warren L. Huberman, PhD, 104 East 40th St, Suite 206, New York, NY 10016; Tel: 212-983-6225; Fax: 212-692-9305; E-mail: whuberman@verizon.net.

 


 

Abstract

The role of a mental health professional working with surgical weight-loss patients is diverse. Primary responsibilities include the provision of patients’ evaluations prior to surgery and either individual or group counseling after surgery. Consultation with the surgeon at various points of patient care is also common. While there is no consensus regarding the content of pre-surgical evaluations or the criteria used to exclude patients from surgery, it is generally accepted that the evaluation is necessary and beneficial. Research supports the benefits of post-surgical mental health services as well. This article suggests pre-surgical evaluations should not primarily focus on psychopathology but on patient expectations and preparedness for the behavioral and emotional changes following surgery. Common reasons patients present for post-operative psychotherapy are reviewed and a stage model of psychological change following surgery is presented.

 

Introduction

It is a pleasure to contribute to this issue on psychological considerations of bariatric surgery. I began working as the consulting psychologist to the New York University (NYU) Program for Surgical Weight Loss in 2000 and have had the good fortune of working with Christine Ren Fielding, MD, George Fielding, MD, and Marina Kurian, MD. The field has changed in numerous ways since 2000, and the knowledge base regarding the psychological impact of weight-loss surgery has grown considerably.

When I was first introduced to bariatric surgery, I was quite skeptical. Having worked extensively as a cognitive-behavioral psychologist focusing on health-behavior change, I was leery that bariatric surgery was another hoax or quick fix for obesity. After having the privilege to work with >5,000 patients, I think that bariatric surgery may represent the only empirically valid treatment for morbid obesity.

In recent years, the use of bariatric surgery as a treatment for obesity has increased significantly, a trend that will grow as obesity rates continue to climb.1 The number of patients presenting for surgery may also increase, as research continues to demonstrate the benefits to both physical health2 and various aspects of psychological well-being and quality of life (QOL).3 The objective of this article is to overview the role of the mental health professional working with surgical weight-loss patients both before and after surgery and to share observations based on my experience with this population.

 

The Role of the Mental Health Professional

Most surgical weight-loss practices adopt a multidisciplinary approach and have accepted that this is needed to help patients achieve success from bariatric surgery.4 The definition of “success” from weight-loss surgery should extend beyond weight loss per se and include improvements in patients’ QOL as well. A mental health professional is typically a member of the team along with nurses, a nutritionist, surgeons, and other clinical staff.

Common responsibilities of a mental health professional in a bariatric surgery program include conducting pre-surgical psychological evaluations, running support groups, and providing individual psychological services to patients before and after surgery. However, there is much variability from program to program. Some programs require pre-surgical psychological evaluations of all patients while others do not.5-10 Numerous programs offer support groups while others do not. This author is unaware of any program that requires patients to participate in ongoing psychological counseling following surgery although some may recommend this practice and make such services available. At least one study has demonstrated that participation in psychotherapy can result in increased weight loss following surgery.11

 

Pre-surgical Evaluations

Both the Surgical Review Corporation and the American College of Surgeons require the involvement of mental health experts in screening bariatric patients for their respective accreditation processes. Numerous experts agree that psychopathology and a number of pre-morbid psychological difficulties can have an effect on post-operative success.12-13 However, findings of studies investigating underlying psychopathology or other emotional obstacles in the bariatric population have yielded inconsistent results. Early studies seemed to suggest there was no greater incidence of psychopathology among the morbidly obese.

Recent studies suggest that morbidly obese patients may have significant symptoms of depression, eating disorders, poor body image, low QOL, and other coexisting mental disorders.5,14-20 In addition to attempting to avoid post-operative psychiatric crises, there is also a strong desire for surgical weight-loss practices to avoid legal proceedings in the event of an adverse surgical outcome. For example, a surgeon would have difficulty defending him- or herself against a legal proceeding from a patient with poorly controlled bipolar disorder who experienced an adverse surgical outcome if the surgeon made little effort to identify and evaluate that such a pre-morbid psychiatric history was present. Such occurrences are commonly reviewed at bariatric conferences and in the general literature.21-26

Interestingly, there is still little consensus as to what the contents of a psychological evaluation should be. Some professionals use structured inventories and psychological instruments such as the Minnesota Multiphasic Personality Inventory-2, Medical Outcomes Study 36-item short form health survey, and a variety of instruments that assess the presence and severity of eating disorders while other professionals rely primarily on a structured clinical interview.27 There is little evidence that any method or instrument of assessment is superior in either identifying inappropriate candidates for surgery or predicting long-term success from surgery.

There is also little consensus as to what specific psychological factors predict outcome, despite the increased focus on inventories or structured tests to identify such variables (GM Boulton-Lewis, unpublished material, 2008).6,10 Numerous variables, including age, gender, socioeconomic status, comorbidities, pre-operative body mass index, prior weight-loss attempts, eating disorders, disordered eating, personality disorders, motivational factors, history of sexual abuse, and social support, among others, have all received some investigation into their effect on surgical outcome, yet none have demonstrated any consistent effects (GM Boulton-Lewis, unpublished material, 2008).

 

Post-Operative Care and Support

Mental health services can be provided as either a prophylaxis against the occurrence of difficulties or a way to address them as they occur. When patients struggle to achieve satisfactory weight loss and medical explanations are inadequate, it is reasonable to consider that psychological variables may be involved. At these times, the surgeon can consult with the mental health professional regarding a difficult case or could refer the patient for psychotherapy.

In addition, several weight-loss surgery programs offer post-operative support groups. These groups may be run by a professional or by patients themselves. There is some debate as to whether support groups or therapy groups are more appropriate28; however, there is little debate that such groups are helpful and desirable. Studies have demonstrated that patients who attended support groups following surgery lost more weight than those who did not attend.29,30 Another study noted that the most highly valued aspect of overall treatment was the provision of continuing care followed by group supports.31

 

Personal Experience

Pre-surgical Evaluations

My initial role as the consulting psychologist to the NYU Program for Surgical Weight Loss was to conduct pre-surgical psychological evaluations. I was familiarized with the types of surgeries, current literature, and nature of the information she wanted me to acquire through the evaluation. My objective in conducting the evaluations was to follow generally accepted practices and to address particular questions and concerns. My objectives for the pre-surgical evaluations have evolved to include the following, as shown in Table 1.

 

 

I created a questionnaire that assesses eating habits, social support, weight-loss history, and mental health history among other areas and have revised it over the years. The questionnaire serves as a template that would enable me to take the patient through a structured yet simple process that is more like a conversation than a clinical interview.

Patients are often anxious about the evaluation because they either have never met with a mental health professional or fear that they will disclose information that will disqualify them from surgery. Patients who have never met with a mental health professional will often ask where the couch is, which is a prompt to explain the objectives of this meeting.

The majority of patients with anxiety fear they may disclose something that will disqualify them from having surgery. I inform patients that this is rare and would most likely be their decision. I have recommended that a surgeon deny surgery to a patient in only a few cases. I can generally explain to the patient why I believe he or she is not presently suitable for surgery and have him or her take steps to address my concerns before moving forward.

It is important to understand the context in which the patient is seeking surgery. One may ask how they learned about it, why they have chosen the present time to pursue surgery, and what the “tipping point” was. The latter question often indicates the patient’s primary objective in having surgery and what his or her expectations are from surgery. It is the opinion of this author that patients do not have surgery simply to lose weight but to accomplish what they believe “thinnerness” will provide. Some patients have dieted for so long that they forgot that weight loss in and of itself is not the final objective. Such patients may not be psychologically prepared for surgery. For most patients, goals include improvements in physical functioning, improved esteem, improved health, and improved interpersonal relationships.

Interestingly, a primary objective in having surgery cited by an overwhelming number of patients is to end the psychological exhaustion from dieting and chronic feelings of failure for their inability to lose weight. Most patients that present for surgery have successfully lost weight before and many have lost >50 pounds on more than one occasion. Unfortunately, most patients believe that maintaining such weight loss with diet and exercise is commonplace and indicate that their family and friends believe this as well, although virtually all clinical research suggests this is hardly the case. For this reason, many patients report feeling guilt and shame over their resorting to surgery as opposed to losing weight the “normal” way. I commonly dispute this notion and refer patients to the clinical literature on this subject.32-34

When patients recognize that the objective is not to try to disqualify them, the assessment becomes a conversation more than an evaluation. For many, this meeting will be their only interaction with a mental health professional, and it is my responsibility that they leave the meeting with a favorable impression of our profession. In doing so, I believe that patients may be more willing to seek out help should the need arise in the future.

The evaluation is as much educational as it is an assessment. In past years, I spent a great deal of time evaluating psychopathology. Colleagues indicated their practice of disqualifying candidates if they expressed a history of major depressive disorder (MDD), suicidality, substance abuse, eating disorders, and other issues. I have since worked with individuals who have had histories of numerous diagnoses and many have done well in terms of both weight loss and improvements in QOL. I continue to assess the presence of Axis I and II pathology but move on to other areas if these issues are absent or are well controlled. This focus on areas beyond psychopathology during the pre-surgical evaluation is receiving further support.35

In the experience of myself and colleagues at NYU, patients with histories of psychopathology, if appropriately managed in follow-up care, can react well. In fact, one study found that patients who met criteria for MDD before surgery did better than non-depressed patients in terms of total weight loss.36 It does not appear that the presence of any particular personality type, trait, or characteristic assures an unsatisfactory outcome from surgery.

Another objective is to encourage the patient to think about life beyond surgery. I ask patients to consider the issues they believe cause behavioral and emotional difficulties after surgery and how they would address them should they occur. Most patients understand the rationale for seeking help if they struggle to lose weight. Fewer patients understand why I ask about potential emotional difficulties that could arise should they be successful in losing weight. Most cannot see weight loss as anything other than desirable, but for patients who see beyond that particular end, they understand completely.

Patients who have been sexually abused or who are socially anxious are often aware of, and have reservations about, making their body more appealing to others. Such patients often report feeling “invisible” in their obesity and are concerned about becoming more “visible” to others following surgery. Numerous morbidly obese patients report that others have ignored them, failed to make eye contact, or rolled their eyes and sighed when they came near. They anticipate that social interactions will change considerably when they begin to lose weight and some have anxiety about these changes.

Patients also express concern that the expectations they have of themselves and that others have of them will change. Such patients acknowledge their weight as a “grand excuse” for shortcomings in various areas of their lives and recognize that improvements in these areas will be expected as they lose weight. For example, many patients fear that they will feel pressure to begin dating now that they are thinner or to begin interviewing for a new job now that concern about weight discrimination has diminished.

It has been my experience that most morbidly obese patients either are, or can become, suitable candidates for surgery. If a patient appears unsuitable, it is likely that he or she is simply not ready at that time. Many patients have presented for surgery in the midst of other issues (ie, divorce, recent loss of a loved one), and when I suggest that they wait until such issues are resolved, it is generally well received. For the vast majority of patients, the medical and psychological benefits of bariatric surgery significantly outweigh its potential consequences so much that there must be an extraordinary reason to deny a patient this opportunity. For this reason, it is imperative that the pre-surgical evaluation is conducted by a clinician who has expertise in the field, so that patients are not inappropriately screened out of surgery, and that those who are allowed to proceed are fully educated and emotionally prepared to do so.

 

Surgical Weight-Loss Patients in Follow Up

Almost all patients who have followed up with me after surgery have been successful from the perspective of weight loss. Most are seeking assistance in making the emotional and behavioral adjustments in their personal and social lives that their weight loss has necessitated. I have yet to speak to a patient who has expressed regret with his or her decision to have surgery. Most patients express satisfaction with the outcome of their surgery, including many who have experienced complications related to surgery. Weight-loss surgery is a powerful tool that enables dramatic weight loss and helps patients to make significant life changes. Therefore, weight-loss surgery should be made available to the majority of patients unless extraordinary circumstances suggest otherwise.

Interestingly, some of the issues that have received significant media coverage have not been common concerns among my patients. I have yet to work with a patient complaining of “food mourning,” wherein one experiences the loss of eating as a primary mechanism to cope with negative emotions because they cannot eat in the manner they did before surgery. Similarly, I have seen only one or two patients who reported increased consumption of alcohol or other substances following surgery (ie, “addiction transfer”). Much has been discussed on this topic and more research is required37 before any conclusions are drawn. In circumstances where my patients have reported increased alcohol consumption following surgery, it has generally been a natural consequence of becoming more socially active after losing weight and not a cause for alarm. However, there are physiologic changes in the way alcohol is absorbed and metabolized, particularly following gastric bypass and other malabsorptive surgeries, and patients need to be aware of the potential problems associated with this phenomenon.

I have seen numerous people who continued to have issues with emotional eating and binge eating following surgery, but many of these patients achieved expected weight loss and did not report dissatisfaction from surgery. These eating issues can continue to be addressed during follow-up but do not necessarily need to be “cured” before surgery is indicated.

 

A Stage Model of Psychological Change Following Bariatric Surgery

In my experience, patients who present for bariatric surgery can be viewed as being in one of two groups: those who are generally satisfied with their lives and those who are not. Those in the former group generally want to lose weight to address health concerns or to stop their weight from interfering with their ability to enjoy their lives as they are. Such patients usually adjust well after surgery, as their primary objective is to lose weight to better enjoy what is already present in their lives.

Those in the latter group are typically the patients who present for post-operative psychotherapy; their lives remain unsatisfying despite the weight loss. Such patients often have impaired esteem, poor body image, unsatisfying or non-existent intimate relationships, minimal or unsatisfying social contacts, and other issues that need to be addressed. For these patients, losing weight may be the easy part. I often tell patients that “fat body goes away faster than fat brain,” explaining that losing the weight takes less time than making the psychological adjustments to the weight loss. Many continue to emotionally feel like their formerly obese selves long after the weight has been lost. Making the life changes that enable them to achieve a greater QOL, the true “success” that I referred to earlier is a more difficult and time-consuming task.

By my observation, many patients go through a series of four stages in making the psychological adjustments to dramatic weight loss following bariatric surgery (Table 2). During the first stage, the focus is on maintaining compliance with dietary rules and on losing weight. Choosing the right foods and learning how to eat properly are of primary concern. Emotionally, there can be excitement from losing weight or apprehension if complications are experienced and weight loss is slow.

 

 

During the second stage, patients may begin to incorporate other tools such as dietary change and exercise and are trying to achieve weight-loss goals whether measured by pounds or by sizes. Rudimentary psychological changes occur such as learning to accept compliments and adjusting to changes in social interactions. Patients are in pursuit of their weight-loss goal and the changes they anticipate will occur when that goal is reached.

During the third stage, patients have achieved or approximated major milestones such as losing 75 or 100 pounds or achieving a desired size. Many will punctuate their accomplishment through a physical achievement or by taking a major step in their personal lives. I have had numerous patients run a marathon or take a physically demanding vacation while others will post their profile on an Internet dating site or begin attending social events. This stage involves experimentation and risk taking as if to demonstrate to themselves and others that they are truly a new person.

The fourth stage can be the most enduring and difficult. It is the stage during which depression and other emotional difficulties are most likely to occur. In this stage, patients begin to adjust to life after weight loss. The life-long objective to defeat obesity in terms of numerical weight may have been accomplished. Friends and family are no longer cheering and the weight loss has become old news. The focus of their life needs to transition from losing weight to adjusting to life in a thinner body and moving beyond weight-related objectives. This is the stage during which changes in one’s personal, social, and professional lives are to occur and is thus ongoing. Success in working through this stage will define overall success from bariatric surgery for many patients.

 

Conclusion

There is a significant contribution that mental health professionals can and do make to bariatric surgery patients and surgeons alike. They play a vital role in patient selection, preparation, and education before surgery and inpatient care following surgery. In many regards, the treatment of morbid obesity through bariatric surgery is as much psychological as it is physical. The work is rich and extremely gratifying; it can have a great impact on patient outcomes. In addition, as the field is growing with the rising number of patients undergoing bariatric surgery, familiarity with the issues faced by these patients is necessary.

There is a unique quality in working with bariatric surgery patients as well. When Dr. Ren Fielding and I met 7 years ago, I asked her what motivated her to work with the morbidly obese. I was touched by her reply and have since adopted it as my own. Her reply was that “surgery is generally about saving lives…weight-loss surgery is often about giving life.” PP

 

References

1.    Steinbrook R. Surgery for severe obesity. N Engl J Med. 2004;350(11):1075-1079.
2.    Maggard MA, Shugarman LR, Suttorp M, et al. Meta-analysis: surgical treatment of obesity. Ann Intern Med. 2005;142(7):547-559.
3.    Wadden TA, Sarwer DB, Fabricatore AN, Jones L, Stack R, Williams NS. Psychosocial and behavioral status of patients undergoing bariatric surgery: what to expect before and after surgery. Med Clin North Am. 2007;91(3):451-469.
4.    Buchwald H. Bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. J Am Coll Surg. 2005;200(4):593-604.    
5.    Greenburg I, Perna F, Kaplan M, Sullivan MA. Behavioral and psychological factors in the assessment and treatment of obesity surgery patients. Obes Res. 2005;13(2):244-249.
6.    Lemont D, Moorehead MK, Parish MS, Reto CS, Ritz SJ. Suggestions for the pre-surgical psychological assessment of bariatric surgery candidates. Gainesville, FL: American Society for Metabolic and Bariatric Surgery; 2004.
7.    Sogg S, Mori DL. The Boston interview for gastric bypass: determining the psychological suitability of surgical candidates. Obes Surg. 2004;14(3):370-380.
8.    Fabricatore AN, Crerand CE, Wadden TA, Sarwer DB, Krasucki JL. How do mental health professionals evaluate candidates for bariatric surgery? Survey results. Obes Surg. 2006;16(5):567-573.
9.    Buchwald H. Bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. J Am Coll Surg. 2005;200(4):593-604.
10.    Wadden TA, Sarwer DB. Behavioral assessment of candidates for bariatric surgery: a patient-oriented approach. Surg Obes Rel Dis. 2006;2(2):171-179.
11.    Nicolai A, Ippoliti C, Petrelli MD. Laparoscopic adjustable gastric banding: essential role of psychological support. Obes Surg. 2002;12(6):857-863.
12.    Simon GE, Von Korff M, Saunder K, et al. Association between obesity and psychiatric disorders in the US adult population. Arch Gen Psychiatry. 2006;63(7):824-830.
13.    Herpertz S, Kielmann R, Wolf AM, Hebebrand J, Senf W. Do psychosocial variables predict weight loss or mental health after obesity surgery? A systematic review. Obes Res. 2004;12(10):1554-1569.
14.    Larsen JK, van Ramshorst B, Geenen R, Brand N, Stroebe W, van Doornen LJ. Binge eating and its relationship to outcome after laparoscopic adjustable gastric banding. Obes Surg. 2004;14(8):1111-1117.
15.    Kinzl JF, Schrattenecker M, Traweger C, Mattesich M, Fiala M, Biebl W. Psychosocial predictors of weight loss after bariatric surgery. Obes Surg. 2006;16(12):1609-1614.
16.    Carpenter KM, Hasin DS, Allison DB. Relationships between obesity and DSM-IV major depressive disorder, suicide ideation, and suicide attempts: results from a general population study. Am J Public Health. 2000;90(2):251-257.
17.    Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW. Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Am J Epidemiol. 2003;158(12):1139-1147.
18.    Allison KC, Stunkard AJ. Obesity and eating disorders. Psychiatr Clin North Am. 2005;28(1):55-67.
19.    Berkowitz RI, Fabricatore AN. Obesity, psychiatric status, and psychiatric medications. Psychiatr Clin North Am. 2005;28(1):39-54.
20.    Wadden TA, Butryn ML, Sarwer BD, et al. Comparison of psychosocial status in treatment-seeking women with class III vs. class I-II obesity. Surg Obes Rel Dis. 2006;2(2):138-145.
21.    Lindstrom W. Professional liability and risk management. Presented at: 19th Annual Meeting of the American Society for Metabolic and Bariatric Surgery; June 24-28, 2002; Las Vegas, NV.
22.    Saxton J, Corboy PH, Sheldon A. Bariatric surgery: what the plaintiff’s lawyers think, the defense lawyers, and most importantly the jurors! Presented at: 23rd Annual Meeting of the American Society for Metabolic and Bariatric Surgery; June 26-July 1, 2006; San Francisco, CA.
23.    Saxton JW. Reducing your bariatric risk while enhancing your program. Presented at: Adding, Updating, and Expanding Bariatric Surgery Centers of Excellence Hospitals and Health Systems Conference; March 8, 2007; San Francisco, CA.
24.    Wittgrove AC. An interview with Alan C. Wittgrove, MD. Bariatric Times. 2007;4(3):13-16.
25.    Wong-Swartz E. Minimizing risk exposure in bariatric surgery. Bariatric Times. 2006;3(5):42-44.
26.    Eagan MC. Bariatric surgery: malpractice risks and risk management guidelines. Am Surg. 2005;71(5):369-375.
27.    Wadden TA, Sarwer DB, Womble LG, Foster GD, McGuckin BG, Schimmel A. Psychosocial aspects of obesity and obesity surgery. Surg Clin North Am. 2001;81(5):1001-1024.
28.    Janeway JM, Sparks K. Support versus therapy: have you got it right? Bariatric Times. 2007;4(9):1,14-17.
29.    Elakkary E, Elhorr A, Aziz F, Gazayerli MM, Silva YJ. Do support groups play a role in weight loss after laparoscopic adjustable gastric banding? Obes Surg. 2006;6(3):331-334.
30.    Latner JD, Stunkard AJ, Wilson GT, Jackson ML. The perceived effectiveness of continuing care and group support in the long-term self-help treatment of obesity. Obesity (Silver Spring). 2006;14(3):464-471.
31.    Song Z, Reinhardt K, Buzdon M, Liao P. Association between support group attendance and weight loss after Roux-en-Y gastric bypass. Surg Obes Relat Dis. 2008;4(2):100-103.
32.    Brownell KD. Obesity: understanding and treating a serious, prevalent, and refractory disorder. J Consult Clin Psychol. 1982;50(6):820-840.
33.    Tsai AG, Wadden TA. Systematic review: an evaluation of commercial weight loss programs in the United States. Ann Intern Med. 2005;142(1):56-66.
34.    Mann T, Tomiyama AJ, Westling E, Lew AM, Samuels B, Chatman J. Medicare’s search for effective obesity treatments: diets are not the answer. Am Psychol. 2007;62(3):220-233.
35.    Bauchowitz A, Azarbad L, Day K, Gonder-Frederick L. Evaluation of expectations and knowledge in bariatric surgery patients. Surg Obes Rel Dis. 2007;3(5):554-558.
36.    Averbukh Y, Heshka S, El-Shoreya H, et al. Depression score predicts weight loss following Roux-en-Y Gastric Bypass. Obes Surg. 2003;13(6):833-836.
37.    Sogg S. Alcohol misuse after bariatric surgery: epiphenomenon or “Oprah” phenomenon? Surg Obes Rel Dis. 2007;3(3):366-368.

 

Needs Assessment: Weight-loss surgery patients present with issues specific to the weight-loss surgery experience and substantial weight loss. Awareness of the challenges these patients typically face will enable physicians to provide appropriate health and mental health care.


Learning Objectives:

• Identify at least four positive interpersonal changes likely to occur after weight-loss surgery.
• Identify at least four potential interpersonal challenges arising after weight-loss surgery.
• Provide medical or mental health care sensitive to interpersonal changes after weight-loss surgery.


Target Audience:
Primary care physicians and psychiatrists.

CME Accreditation Statement: This activity has been planned and implemented in accordance with the Essentials and Standards of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Mount Sinai School of Medicine and MBL Communications, Inc. The Mount Sinai School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation: The Mount Sinai School of Medicine designates this educational activity for a maximum of 3 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Faculty Disclosure Policy Statement: It is the policy of the Mount Sinai School of Medicine to ensure objectivity, balance, independence, transparency, and scientific rigor in all CME-sponsored educational activities. All faculty participating in the planning or implementation of a sponsored activity are expected to disclose to the audience any relevant financial relationships and to assist in resolving any conflict of interest that may arise from the relationship. Presenters must also make a meaningful disclosure to the audience of their discussions of unlabeled or unapproved drugs or devices. This information will be available as part of the course material.

This activity has been peer-reviewed and approved by Eric Hollander, MD, chair and professor of psychiatry at the Mount Sinai School of Medicine, and Norman Sussman, MD, editor of Primary Psychiatry and professor of psychiatry at New York University School of Medicine. Review Date: June 23, 2008.

Drs. Hollander and Sussman report no affiliation with or financial interest in any organization that may pose a conflict of interest.

To receive credit for this activity: Read this article and the two CME-designated accompanying articles, reflect on the information presented, and then complete the CME posttest and evaluation. To obtain credits, you should score 70% or better. Early submission of this posttest is encouraged: please submit this posttest by August 1, 2010 to be eligible for credit. Release date: August 1, 2008. Termination date: August 31, 2010. The estimated time to complete all three articles and the posttest is 3 hours.

Primary Psychiatry. 2008;15(8):61-66

 

Drs. Sogg and Gorman are staff psychologists at the Massachusetts General Hospital Weight Center and instructors in psychology at the Harvard University School of Medicine in Boston, MA.

Disclosure: Drs. Sogg and Gorman report no affiliation with or financial interest in any organization that may pose a conflict of interest.

Please direct all correspondence to: Stephanie Sogg, PhD, MGH Weight Center, 50 Staniford St, 4th Fl, Boston, MA 02114; Tel: 617-726-6761; Fax: 617-724-6565; E-mail: ssogg@partners.org.

 


 

 

Abstract

Weight-loss surgery literature suggests that the majority of patients experience the changes that occur as a result of dramatic weight loss after weight-loss surgery as being overwhelmingly positive. However, even positive change may pose a variety of psychosocial challenges. In the case of weight-loss surgery, these changes and challenges often manifest themselves in a variety of interpersonal realms, including everyday social interactions and relationships with close friends and loved ones. In addition, patients must learn to function in certain interpersonal situations they may not have had to navigate in years or have never encountered before. This article examines some of the interpersonal changes and challenges arising after weight-loss surgery, with a brief review of empirical literature on this topic. It concludes with a discussion of the ways healthcare providers can facilitate smooth adjustment to interpersonal changes after weight-loss surgery.

 

Introduction

Due to the rapidly increasing prevalence of weight-loss surgery in recent years,1-4 healthcare professionals of all disciplines are more likely to encounter weight-loss surgery patients in their clinical practices. Therefore, it is important for clinicians who do not specialize with this population to become knowledgeable about weight-loss surgery and the common post-operative experiences patients face to ensure the provision of appropriate care and referrals.

A growing body of empirical literature suggests that after weight-loss surgery, the majority of patients experience overwhelmingly positive changes,5-10 including dramatic improvements in medical comorbidities2,11-16; enhanced energy, mobility, mood, and self-esteem; and increased desire and ability to engage in a variety of activities.5,6,8,11,17 However, even positive change may pose a variety of psychosocial challenges.5

For weight-loss surgery patients, these changes and challenges often manifest themselves in a variety of interpersonal realms. Weight-loss surgery may affect spheres ranging from everyday social interactions to relationships with close friends and loved ones. In addition, patients must learn to function in certain interpersonal situations they may not have had to navigate in years or have never encountered before. This article examines some of the interpersonal changes and challenges arising after weight-loss surgery, including a brief review of empirical literature on this topic. Ways to facilitate smooth adjustment to interpersonal changes after weight-loss surgery are discussed as well.

It should be noted that there is a relative dearth of empirical literature examining this topic6; many of these studies were published decades ago, involve small samples, and pertain to bariatric procedures that are now rarely performed. Examination of interpersonal outcomes tends to be done in broad strokes,6 with patients rating general satisfaction or improvement, rather than focusing on specific types or mechanisms of change. Thus, patient report and clinical experience must often be used to inform the effect of weight-loss surgery on interpersonal functioning.

 

Everyday Social Interactions

Positive Changes

Almost immediately after surgery, patients report receiving increased attention from supportive family and friends around taking an important step in addressing their health risks. As patients lose weight, positive attention often takes the form of compliments, which many patients report finding pleasurable and gratifying. In addition, patients frequently report that both strangers and acquaintances tend to be more likely to approach and generally act more positively toward them. Patients typically attribute these changes directly to improved appearance. Though this may be the case, it is likely that this change is partly attributable to changes in the way the patients interact with others. As their mood, self-confidence, and self-esteem improve, patients may approach others more often and more positively, effecting a change in how others respond to them.

 

Challenges

While receiving compliments is pleasurable for most people, it is not uncommon for weight-loss surgery patients to feel uncomfortable when this occurs, especially if they were not accustomed to receiving compliments in the past. Numerous patients express concern that they will appear conceited if they do not downplay or reject compliments. Frequently, it takes some time before a patient’s self-concept becomes consistent with his or her changed outward appearance.18 Therefore, compliments may be perceived as uncomfortably discordant with the patient’s self-image; one patient described the experience of receiving a compliment as causing “a short-circuit in my brain.” In other cases, patients simply have not developed the basic skill of responding to a compliment by merely saying, “Thank you.” Fortunately, this skill can be developed through a very brief intervention of guided role-playing (and some practice), greatly easing this type of social transaction.

For some patients, changes in the way others respond to them can be experienced as insulting. Some patients report feeling resentful about being treated better by other people simply because they lost weight.5,6 Patients may interpret a sudden increase in compliments to mean that before surgery, people found them unappealing; one patient reported responding to enthusiastic compliments with the thought, “Wow, what must they have thought of me before?”

Before weight-loss surgery, patients frequently report experiencing significant stigma and discrimination related to their weight.6,19-23 Numerous patients complain about bias at work, within their families, and from strangers; empirical investigations substantiate the reality of widespread prejudice and discrimination against individuals with obesity.21,22,24-30 It has been found that medical professionals,18,25,31-35 even those who specialize in studying and treating obesity,29,36 hold such prejudices. It has been noted that obesity is “one of the last acceptable forms of prejudice” in our society.37 Further, unlike members of other stigmatized groups, it has been found that people with obesity tend to internalize these biases.20,22,25,28,38,39 Because of the stigma related to obesity, research has demonstrated that people with obesity are more susceptible to depression and lowered self-esteem.40-46 Fortunately, after weight-loss surgery, as patients lose weight, they encounter fewer of these experiences.23 However, they often remain acutely aware of and troubled by the prejudice that exists toward individuals with obesity in Western culture.5 It can be particularly uncomfortable when patients catch themselves engaging in this type of stigmatizing behavior. One patient described feeling horrified and saddened when, having just been cut off by another driver in a parking lot, she found herself making disparaging observations about that driver’s being overweight.

Weight-loss surgery may also lead to unwanted inquiries by others. For many reasons, the topic of weight-loss surgery seems to be quite interesting to the lay public, and weight-loss surgery patients often find themselves reluctantly assuming the role of “weight-loss surgery ambassador” to their family and friends. Patients report being subjected to frequent questions about the surgery and post-operative regimen. Although patients often report being enthusiastic about their experiences and wanting to share them with others, some patients find it tiresome to answer repetitive questions about weight-loss surgery or find that conversations with others too frequently focus on this topic. In addition, patients sometimes report being asked intrusive personal questions, such as “How much weight have you lost?” or “What did you weigh before?” Patients also often report that others appear to be inordinately curious about what, how much, and how fast they can eat.

One of the more distressing challenges that weight-loss surgery patients sometimes face is being subjected to the opinions of people who mistakenly believe that weight-loss surgery is somehow “cheating” or “taking the easy way out,” when the patient “should have been able to lose the weight on his or her own.” This is yet another expression of the bias and misapprehensions about obesity among the general public, and it leaves the patient in an unpleasant position of having to justify his or her decision to have surgery. Unfortunately, in Western society, obesity is often believed to be the result of a psychiatric or behavioral disorder, laziness, or failure of will power.24-26 However, a growing body of research strongly indicates that biologic factors are very powerful in determining body weight.26,47 In fact, it has been estimated that 40% to 85% of the individual variation in obesity may be attributable to genetic factors.48,49 In addition, once it has developed, obesity is notoriously resistant to nonsurgical treatments such as lifestyle change or weight-loss medications regardless of etiology,12,50-56 leaving weight-loss surgery as most patients’ best hope for improvement or reversal of the dangerous comorbidities of obesity.1,12,14,15,57-59 It is often incumbent upon weight-loss surgery patients to explain these facts to others, which can be tedious at best and, at worst, demoralizing.

 

Intimate Relationships

Positive Changes

Another realm of interpersonal changes after weight-loss surgery is in the sphere of intimate relationships: close friendships, family relationships, and romantic partnerships. Before surgery, patients frequently report that their weight diminishes both the ability and the desire to engage in a variety of activities.42,60,61 After weight-loss surgery, improvements in health, mobility, energy, mood, and self-confidence render patients more able and eager to engage in a wider spectrum of activities.5,6,10,11,18,62 This can translate into more enjoyable time spent with friends and loved ones and participation in or rediscovery of activities and hobbies that had been abandoned in the past. Patients report being able to take long walks with their spouses or chase their grandchildren around the backyard. One patient reported feeling elated by the simple pleasure of being able to cook a meal for her spouse, an activity that was impossible before weight-loss surgery, as she could not stand at the stove for more than a few minutes at a time.

Additionally, improved mood and self-confidence make social situations more enjoyable after weight-loss surgery. Patients report that after weight-loss surgery, they appreciate becoming free of the constant awareness of their size; the fear of being evaluated negatively by others diminishes.6,11,18,62,63 Patients who, before surgery, tended to avoid parties and other social situations because they were self-conscious about their appearance no longer feel they have to refuse invitations.

The vast majority of weight-loss surgery patients report that having surgery has affected their romantic relationships in a positive way.8,62,64-69 As noted above, weight-loss surgery offers patients the opportunity to engage in more shared activities with their partners62,68 or to resume a larger share of household responsibilities. Additionally, weight-loss surgery appears to lead to significant improvements in most patients’ sexual functioning.62,64,67,70,71 Patients often report that improved mood, body image, and self-confidence significantly increase their sexual desire and level of comfort with physical intimacy.8,66,70 Sexual activity becomes mechanically easier due to increased endurance, improved mobility, and smaller body size.5,66,70 Some patients report that their partners show a renewed or increased sexual interest toward them as they lose weight.62 One study70 found that patients’ partners reported being even more satisfied with sexual changes after weight-loss surgery than the patients themselves.

 

Challenges

Despite the positive changes described, challenges may arise in close relationships after weight-loss surgery. As the patient loses weight, friends or family members may become envious or competitive.5,6,72 It is not uncommon for patients to report that a close friend or relative has commented, “Wow, you are getting close to my size, now–I should go on a diet!” In some cases, the weight-loss surgery patient was part of a friendship, family, or social group in which he or she played the role of “the fat one,” someone who was less assertive or posed less of a threat or competition for the opposite sex. As the patient loses weight after surgery, this dynamic may be changed, disrupting the equilibrium of the friendship, family, or social group.

Relationships that in the past had centered around eating, cooking, or visiting restaurants may have to undergo some adjustments after the patient undergoes weight-loss surgery, and friends and family members may also be concerned about losing an “eating buddy.” In Western culture, it can be difficult to find opportunities for socialization that do not focus on food or drink.6 In addition, as patients create healthier eating patterns for themselves, eating in the entire household is likely to be affected. In some cases, patients may feel guilty about the possibility that family meals will be disrupted or worry that loved ones will feel deprived of certain favorite foods. Conversely, some weight-loss surgery patients find that friends or family begin to act as the “food police,” monitoring and commenting on each bite the patient eats. Although this behavior may reflect genuine caring and concern on the part of the friend or family member, it can be quite aversive to the patient.

Another potential challenge is possible sabotage by a friend or family member in the form of exhortations to eat more or expressions of concern about the patient losing too much weight. This type of behavior may be either intentional or unintentional, driven by envy, insecurity, or a lack of knowledge of the post-operative regimen. Examples of this type of challenge can range from a concerned relative repeatedly asking, “Is that all you’re going to eat?” or serving the patient too much at family dinners, to a partner complaining because there is no longer any ice cream in the house or refusing to buy healthier foods for the home.

Although the effect of weight-loss surgery on romantic relationships tends to be overwhelmingly positive, some patients report significant disruption in their romantic relationships. Family systems theory holds that a homeostatic balance is established and maintained within relationships by each member fulfilling his or her specific role in relation to the other. When one person in a relationship changes, this disrupts homeostasis, and if the relationship does not change accordingly, balance will not be re-established and destabilization will occur.73 Empirical investigation of marital changes after weight-loss surgery suggests that relationships that were strong before surgery tend to stay that way, while relationships that were less healthy originally are more likely to be destabilized.17,62,64,66 For example, an improved self-image and feelings of self-worth may make a patient less willing to tolerate a relationship in which he or she is not treated with kindness and respect.5 In one study, wives rated themselves as more sociable and interesting after surgery, while rating their husbands as less sociable and interesting than they did before surgery.63 As the patient develops a stronger sense of self-worth, the balance of power may shift in a friendship or romantic relationship.5 In a healthy relationship, a new, positive equilibrium is reached, while in an unhealthy one, this shift in power may lead to the dissolution of the relationship. Similarly, because of the disability and ill-health that may accompany severe obesity, some patients may have become reliant on their partners in a variety of ways. As health improves and autonomy grows, the relationship may be disrupted if, as the patient asserts newfound independence, his or her partner feels that he or she has lost an important role or is no longer needed.5,62,63,72 In addition, some patients report that their partners become jealous, or express anxiety about patients leaving the relationship as they lose weight and become more attractive to others.5,66,72

It is worth noting that although patients commonly report improvements in their sexual functioning and sexual relationships after weight-loss surgery, a significant minority of patients report a negative impact on their sex lives.66 For some, wound complications or other early surgical sequelae interfere with sexual functioning.62,70 Some patients may experience a short-term decrease in sex drive after weight-loss surgery5,62,66 Though most patients experience improvement in their body image and improvements in their sexual functioning, for some patients, excess skin, which can develop after a significant weight loss, may actually worsen body image10 and increase inhibitions toward sexual intimacy.66

 

New Experiences

As weight-loss surgery patients lose weight and regain energy, mobility, and self-confidence, they may begin to find themselves in a variety of situations that they have not encountered in the past, or which they had avoided for some time because of the functional or psychological impact of their obesity.5,74 For example, before surgery many patients find that because of their obesity people do not really see or pay attention to them. After losing weight, however, weight-loss surgery patients sometimes note that they are no longer “invisible.”5 Although in general this is likely to be a positive change, it can be uncomfortable and it may take patients time to become accustomed to being “visible” again.

This newfound visibility may lead to increased romantic or sexual attention, which is welcome and exciting for most patients and contributes to improved confidence, mood, self-esteem, and body image. However, for others, this type of attention may be disruptive. Some patients with a history of sexual abuse may find increased sexual or romantic attention to be threatening.5,17 It has been hypothesized that these patients may experience their extra weight as a defense or protective factor that minimizes the risk of receiving sexual attention or finding themselves in sexual situations,41,75,76 and losing this buffer may lead to feelings of vulnerability.5,17 One study found that patients with a history of sexual abuse lost less weight at 12 months post-surgery.71 Another77 found that while there was no difference in weight loss 2 years after surgery between patients with and without a history of sexual abuse, those with an abuse history were significantly more likely to report having had a psychiatric hospitalization in the first 2 post-operative years. However, it is important to note that a history of sexual abuse is not considered to be a contraindication for weight-loss surgery, and research studies have typically found that such a history has no impact on post-surgical weight loss or psychosocial adjustment in the long term.78-81

Even for those patients for whom an increase in romantic opportunities is a welcome change, this new situation may still pose challenges. Some patients, particularly those who are younger at the time of surgery, report that they had never been involved in romantic relationships before and may never have grown accustomed to dating or developed necessary dating “skills.”5 Learning how to navigate the world of romantic relationships can be a complicated experience, even if it is an enjoyable one. For other patients, it may have been years since they were involved in dating, and they may find that their skills are “rusty,” or that the norms in the dating world have changed. For example, expectations about which party asks or pays for the date, or how quickly sexual activity is introduced, may be quite different now than they were when the patient last dated. For some patients, vigilance about sexually transmitted diseases is a new development that requires some consideration. Those whose fertility may have been impaired by their obesity may not appreciate the increased need for protection against unplanned pregnancy. This is particularly problematic, since there is risk for birth defects in pregnancies occurring within the first 12–18 months after weight-loss surgery.82,83

 

Conclusion

Although patients presenting for weight-loss surgery are highly motivated to achieve and maintain significant weight loss, they may not anticipate the impact the surgery could have on their interpersonal functioning. Weight-loss surgery typically results in changes experienced as extremely positive and enriching, especially in the interpersonal realm. However, these changes may also present significant challenges. Clinicians caring for weight-loss surgery patients must be aware of the significant changes and challenges that may arise. As noted above, these may include changes in everyday social interactions and close interpersonal relationships, and facing situations with which the patient had little experience before losing weight. There are numerous opportunities for healthcare providers to facilitate successful adjustment to weight-loss surgery.

This may begin even before surgery, with the pre-operative psychosocial evaluation. This evaluation serves the function of identifying potential post-surgical challenges and affords the opportunity to help the patient to proactively formulate appropriate coping strategies. Educating the patient about potential challenges is an important and powerful tool for enhancing adjustment after surgery.84 Further, the evaluating clinician need not be relegated to the role of “gatekeeper”; a mental health practitioner can also serve as the facilitator of whatever intervention is needed to clear the patient’s path to surgery and increase the safety and efficacy of this important medical procedure.45,84-87

During the perioperative and early adjustment period, clinicians who are mindful of the potential changes and challenges discussed above can provide appropriate psychosocial intervention; this may be done within the surgical program itself or, if no appropriate clinician is on staff, referrals can be made to clinicians in the community who have experience working with weight-loss surgery patients.

It is also important that ongoing psychosocial support is available in the long term after weight-loss surgery.17,84,86,88 It is recommended that routine follow-up visits extend beyond the first 6–12 months after surgery, as many of the challenges described above may emerge at a longer latency after surgery.88 Regular, long-term follow up fosters working relationships in which the patient feels comfortable discussing any challenges that may arise, as well as increasing opportunities for doing so. Programs that incorporate or have a close association with mental health providers can provide appropriate referrals for patients to receive assistance in coping with adjustment to life after weight-loss surgery. In addition, other healthcare providers can be helpful to patients navigating the interpersonal challenges that may arise after weight-loss surgery by being aware of the common issues. Sensitivity to these issues will allow medical and mental health providers to provide better care, make sensitive inquiries during routine visits, and make the appropriate referrals when necessary. PP

 

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37.    Stunkard AJ, Sorensen TI. Obesity and socioeconomic status–a complex relation. N Engl J Med. 1993;329(14):1036-1037.
38.    Puhl RM, Moss-Racusin CA, Schwartz MB. Internalization of weight bias: Implications for binge eating and emotional well-being. Obesity (Silver Spring). 2007;15(1):19-23.
39.    Wang SS, Brownell KD, Wadden TA. The influence of the stigma of obesity on overweight individuals. Int J Obes Relat Metab Disord. 2004;28(10):1333-1337.
40.    Chen E, Bocchieri-Ricciardi L, Munoz D, et al. Depressed mood in class III obesity predicted by weight-related stigma. Obes Surg. 2007;17(5):673-675.
41.    Kalarchian MA, Marcus MD, Levine MD, et al. Psychiatric disorders among bariatric surgery candidates: Relationship to obesity and functional health status. Am J Psychiatry. 2007;164(2):328-334.
42.    Kasen S, Cohen P, Chen H, Must A. Obesity and psychopathology in women: a three decade prospective study. Int J Obes (Lond). 2007;32(3):558-566.
43.    Stout AL, Applegate KL, Friedman KE, Grant JP, Musante GJ. Psychological correlates of obese patients seeking surgical or residential behavioral weight loss treatment. Surg Obes Relat Dis. 2007;3(3):369-375.
44.    van der Merwe MT. Psychological correlates of obesity in women. Int J Obes (Lond). 2007;31(suppl 2):14-18.
45.    Wadden TA, Butryn ML, Sarwer DB, et al. Comparison of psychosocial status in treatment-seeking women with class III vs. class I-II obesity. Obesity (Silver Spring). 2006;14(suppl 2):90-98.
46.    Wadden TA, Sarwer DB, Fabricatore AN, Jones L, Stack R, Williams NS. Psychosocial and behavioral status of patients undergoing bariatric surgery: what to expect before and after surgery. Med Clin N Am. 2007;91(3):451-469.
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48.    Farooqi IS, O’Rahilly S. Genetic factors in human obesity. Obes Rev. 2007;8(suppl 1):37-40.
49.    Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr. 2008;87(2):398-404.
50.    Bray GA, Ryan DH. Drug treatment of the overweight patient. Gastroenterology. 2007;132(6):2239-2252.
51.    Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM. Meta-analysis: the effect of dietary counseling for weight loss. Ann Intern Med. 2007;147(1):41-50.
52.    Elfhag K, Rossner S. Who succeeds in maintaining weight loss? A conceptual review of factors associated with weight loss maintenance and weight regain. Obes Rev. 2005;6(1):67-85.
53.    Foster GD, Makris AP, Bailer BA. Behavioral treatment of obesity. Am J Clin Nutr. 2005;82(1 suppl):230-235.
54.    Mun EC, Blackburn GL, Matthews JB. Current status of medical and surgical therapy for obesity. Gastroenterology. 2001;120(3):669-681.
55.    Wadden TA, Butryn ML, Byrne KJ. Efficacy of lifestyle modification for long-term weight control. Obes Res. 2004;12(suppl):151-162.
56.    Wadden TA, Butryn ML, Wilson C. Lifestyle modification for the management of obesity. Gastroenterology. 2007;132(6):2226-2238.
57.    Adams TD, Gress RE, Smith SC, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8):753-761.
58.    Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724-1737.
59.    Buchwald H. Bariatric surgery for morbid obesity: health implications for patients, health professionals, and third-party payers. J Am Coll Surg. 2005;200(4):593-604.
60.    Fabricatore AN, Wadden TA, Sarwer DB, Faith MS. Health-related quality of life and symptoms of depression in extremely obese persons seeking bariatric surgery. Obes Surg. 2005;15(3):304-309.
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63.    Hafner RJ. Morbid obesity: effects on the marital system of weight loss after gastric restriction. Psychother Psychosom. 1991;56(3):162-166.
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Dr. Robinson is a consultant with Worldwide Drug Development in Burlington, Vermont.

Disclosure: Dr. Robinson has served as a consultant to Bristol-Myers Squibb, Epix, Johnson and Johnson, PGxHealth, Pfizer, and Schering.

 


 

The profound influence of the pharmaceutical and drug devices industry on clinical medicine, medical education, and research is a source of growing concern raised in the medical literature and media.1,2 The potential for bias due to commercial interests prompted editors of leading international medical journals to endorse greater transparency in reporting of clinical trials regarding authorship, financial support, and potential conflict of interest as a prerequisite for reviewing submitted manuscripts.3,4 This editorial posture taken by prestigious medical journals worldwide helped foster legislation that requires advance registration of phase II and III clinical trials prior to study inception.5

Evidence-based medicine has become the accepted standard for the teaching and practice of medicine.6 A basic premise underlying informed decision-making is accurate and complete reporting of clinical trial outcomes. Applying principles of evidence-based medicine to psychiatric practice is essential.7,8 Three recent articles9-11 explore issues of selective reporting of clinical trial data, guest authorship, and ghostwriting in reports of drugs with psychotropic effects.

 

Selective Publication of Antidepressant Efficacy Trials

Academic investigators lacking ties to the pharmaceutical industry conducted a comprehensive review9 of Food and Drug Administration documents pertaining to pre-approval phase 2 and phase 3 efficacy trials of 12 antidepressants. These antidepressants, approved for marketing between 1987 and 2004, involved enrollment of >12,500 adult patients in efficacy trials. FDA medical and statistical review documents for each of the antidepressants were procured through the Freedom of Information Act12 and the FDA Web site.13 Turner and colleagues9 examined efficacy data from randomized, double-blind, placebo-controlled trials reported to the FDA and compared these data with that contained in published reports of efficacy trials for each of these drugs. Only data for approved dosages were included in the analyses. Each efficacy trial is categorized in the FDA Summary Basis of Approval (SBA) document as positive (ie, indicative of efficacy) or negative (ie, inconclusive or no efficacy).

Turner and colleagues9 conducted an exhaustive literature search to identify all placebo-controlled clinical trials published for each of the antidepressants. Their search strategy involved several steps: searching for articles in PubMed; searching for references cited in review articles; searching the Cochrane Central Registry of Controlled Trials; contacting the medical information department of each pharmaceutical sponsor; and finally, contacting in writing by certified letter addressed to the medical-information department of the drug sponsor to request a written response to the query of whether the results of an efficacy trial listed in the SBA document had been published. If none of these steps yielded evidence of publication, it was concluded that the efficacy results for the trial had never been reported.

Comparison of FDA regulatory data with published data included statistical analyses that compared sample sizes as reported to the FDA and in published trial reports, and computed effect-sizes for each drug from data contained in FDA documents versus published reports. A single weighted effect size for each antidepressant was derived by pooling data from published journal articles. This value was compared with the computed effect size from the FDA medical and statistical review documents, which contain complete data sets for each antidepressant, both published and unpublished.

 

Efficacy Outcome and Publication Status

Turner and colleagues9 examined the publication status of FDA-registered antidepressant efficacy trials over the period from the mid-1980s onward. Of 74 clinical trials registered with the FDA and included in the new drug applications of the 12 antidepressants, no evidence of publication was found for 23 (31%) of the placebo-controlled efficacy trials (Table). Unavailability of published data in peer-reviewed journals for 23 of these antidepressants amounts to information on a total of 3,500 patients in therapeutic trials unavailable to public scrutiny.

 

 

In the FDA medical and statistical reviews, it was deemed that 38 of the 74 efficacy trials (51%) were positive studies, and all but one of these trials have been published. The remaining 36 studies (49%) were either negative (n=24) or were considered inconclusive for efficacy (n=12). Of these, 11 studies were published as being positive efficacy trials even though they conflicted with the FDA assessment. Only three of 24 negative efficacy trials (13%) have been published.

An important finding of this analysis is that negative efficacy trials of antidepressants (and presumably, most psychotropics) are infrequently reported in the medical literature. Furthermore, trials with mixed or inconclusive efficacy outcomes are often reported as positive studies, even though the primary outcome measure may have failed to show efficacy and may not be apparent in the report.

 

Effect Sizes of Antidepressants versus Published Data

Turner and colleagues9 computed weighted effect-size values from pooling of journal reports for each antidepressant and compared this value with effect sizes computed from the FDA summary documents. In each instance, the computed effect-size based on the published literature was higher than the effect-size value based on FDA documentation. The weighted effect sizes from the published literature ranged from 11% to 69% higher than the effect sizes computed from FDA data (mean=32%, P<.001). It is interesting that effect sizes using the FDA database ranged from 0.2–0.4 for the 12 antidepressants, where 0.2 is regarded as a small effect size and 0.5 a medium effect size. Effect sizes based on pooled published reports were consistently higher for every one of the 12 antidepressants, and effect size exceeded 0.5 for mirtazapine, paroxetine, and venlafaxine.

The findings of this study should be interpreted cautiously. It must be kept in mind that absence of statistical significance in a trial does not necessarily signify lack of efficacy. There can be valid reasons during the second and third phases of development for trials to fail unrelated to intrinsic efficacy of the agent. Failed and negative trials may result from escalating placebo response rates in efficacy studies, a changing population of depressed subjects recruited primarily by advertisement, or a relative dearth of competent investigators who carefully select and rate patients who are likely to be drug responsive.14,15 There are numerous factors influencing whether results of a study may go unpublished, including failure to submit manuscripts or decisions by journal editors not to accept negative trials. The recently established clinical trial registries and the requirement of journals and the FDA that trials be registered may foster wider dissemination of efficacy outcomes of trials.4,5

 

Guest Authorship and Ghostwriting

Apparent misrepresentation of clinical trial results and manipulation of research articles relating to rofecoxib (Vioxx) has emerged as a result of litigation.1,10,11 Court documents originally obtained during litigation against Merck and Company allowed access to company policies and decision making regarding publication of clinical trial results of rofecoxib.

A recent study10 by authors involved in the litigation and interested in company practices about guest authorship, ghostwriting, and financial disclosures examined several thousand court documents to investigate these issues. Guest authorship is defined as designation of an individual as author who does not meet accepted authorship criteria; that is, an individual who did not make a substantial contribution to the research or writing the manuscript.16 Inspection of the rofecoxib litigation yielded approximately 250 documents relating to publication of clinical trials of rofecoxib and allowed a determination to be made as to use of professional medical writing in manuscript preparation and subsequent recruitment of opinion leaders to be authors. Internal documents revealed that Merck marketing employees commonly hired medical writing companies to ghostwrite scientific review articles and recruited external experts to serve as authors. Recruited authors of ghostwritten papers often served as sole author and received an honorarium. Numerous instances were found where authors did not appear to be involved in the design or conduct of the study or to have made substantive contributions to the manuscript other than minor editing. Among 96 relevant published articles, the authors found that 92% (22 of 24) of published clinical trials disclosed Merck financial support, but only 50% (36 of 72) of therapeutic review articles about rofecoxib disclosed Merck sponsorship or financial compensation of the author.

 

Data Misrepresentation and Selective Reporting

Two biostatisticians, also involved in the rofecoxib litigation and familiar with the clinical data, examined internal documentation relating to three placebo-controlled clinical trials of rofecoxib in the treatment of Alzheimer patients. The authors also conducted their own independent statistical analysis of the safety data from these long-term multicenter trials.11 In April 2001, the drug sponsor conducted an intention-to-treat analysis that revealed increased risk of mortality associated with rofecoxib treatment of cognitive impairment among patients with Alzheimer’s disease, but this analysis was not submitted to the FDA until 2003. Instead, the data reported to the FDA in 2001 as part of a required annual safety update used a variety of counting methods, such as an on-treatment analyses. This type of statistical analysis, unlike a more conservative intention-to-treat analysis, minimized appearance of excess mortality risk with rofecoxib. The drug sponsor also failed to inform investigational review boards of the findings of the intention-to-treat analysis as required. Investigators in the ongoing multi-year study remained blind to this emerging safety data, unlike the Merck research staff, who failed to discern a safety issue. The company allowed the study to continue for 2 more years because of slower than planned enrollment.

A review article, funded by Merck and published in November 2001, based on a meta-analysis of cardiovascular thrombotic events in 23 clinical trials of this cyclo-oxygenase agent included two of the rofecoxib Alzheimer’s disease trials, yet the authors, five of whom were Merck employees, did not take the opportunity to report the mortality findings of the intention-to-treat analysis.11 It was not until July 2003, that a final safety report filed with the FDA furnished this evidence of excess mortality in Alzheimer’s disease patients (Hazard Ratio, 2.71, P<.001). Independent analysis by the authors of the present report of the Alzheimer’s safety data available in 2001 confirms that this excess mortality in elderly patients associated with rofecoxib treatment was known.11

 

Conclusion

Three studies that prompted a recent Journal of the American Medical Association editorial1 examined issues pertaining to the reporting clinical trial data.9-11 Greater than 30% of pre-approval, placebo-controlled, efficacy trials of antidepressants approved in the past 15 years were found never to have been published. Guest authorship and ghostwriting of articles was a frequent practice for a popular drug, later removed from the market for safety reasons. For the same drug, apparent misreporting of mortality data in Alzheimer’s disease patients occurred. Accurate and complete reporting of clinical trial results is essential to the teaching and practice of evidence-based medicine. Precautions taken by medical journals, such as submitting original study protocols and independent statistical analyses, may be necessary to ensure accuracy and transparency of published reports. PP

 

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13.    Center for Drug Research. Food and Drug Administration. Rockville, Maryland. Available at: www.fda.gov/cder/foi/nda. Accessed July 9, 2008.
14.    Robinson DS, Rickels K. Concerns about clinical drug trials. J Clin Psychopharmacol. 2000;20(6):593-596.
15.    Kobak KA, Kane JM, Thase ME, Nierenberg AA. the problem of measurement error in clinical trials: time to test new paradigms? J Clin Psychopharmacol. 2007;27(1):1-5.
16.    Rennie D, Yank V, Emmanuel L. When authorship fails: a proposal to make contributors accountable. JAMA. 1997;278(7):579-585.

 

Dr. Vazzana is clinical assistant professor in the Department of Child and Adolescent Psychiatry at New York University (NYU) School of Medicine and member of the Harris Obesity Prevention Effort at NYU in New York City.

Disclosures: Dr. Vazzana receives grant support from Allergan.
Please direct all correspondence to: Andrea D. Vazzana, PhD, NYU Child Study Center, 577 1st Ave, New York, NY 10016; Tel: 212-263-8843; Fax: 212-263-8662; E-mail: vazzaa01@nyumc.org.

 


 

Focus Points

• Significant psychological changes follow adolescent bariatric surgery.
• Psychological factors and quality of life are important outcomes of surgery.
• A minority of adolescents exhibit poor psychosocial adjustment post-surgery.

 

Abstract

The adverse impact obesity can have on a person’s medical and mental health is overwhelming. As the prevalence and severity of childhood obesity and its related comorbidities continue to swell, there are inadequate effective, long-term solutions for the non-surgical management of morbidly obese youth. Although they are still controversial, refined surgical procedures have improved the safety and efficacy of bariatric surgery. It is being increasingly used with morbidly obese adolescents under the care of a multidisciplinary treatment team. Bariatric surgery typically results in marked weight loss and the resolution or reduction of comorbid conditions. At a more normalized weight, these adolescents often experience substantial life changes in areas that have the potential to positively, and sometimes negatively, alter a person’s quality of life. It is important to understand these complex changes in order to facilitate the adolescent’s positive long-term outcome. Despite their importance, there are limited empirical studies pertaining to adolescent psychosocial outcomes. Current results support the benefits of bariatric surgery in this population, but more rigorous research studies with prospective data collection and long-term follow up are necessary before pediatric bariatric surgery can be officially sanctioned for this special needs population.

 

Introduction

The United States has the worst epidemic of child obesity in the world.1 Seventeen percent of US adolescents are currently obese,2 and the prevalence is expected to progressively increase through at least 2010.1 The severity of obesity in youths has increased as well. Today’s heaviest children are markedly heavier than those from one generation ago.3 Four percent are morbidly obese (Table 1),4,5 and they are likely to remain obese as adults, particularly if at least one parent is also obese.6-8 Medical consequences of obesity are well documented9 and result in earlier mortality,10,11 curtailing the obese individual’s lifespan by 5–20 years.11 Indeed, the obesity epidemic undermines medical advances that would otherwise extend life span.12 Financial costs of the child obesity epidemic are also burdensome. At over $127 million/year, national hospital costs associated with child obesity and its comorbidities have tripled in the past 20 years.13

 

 

However, the greatest cost of obesity might be the psychological impact resulting from social stigma and discrimination.14,15 The pervasiveness of societal bias against obesity is widespread; it has been called the last “acceptable” form of discrimination.16 Obesity has particularly devastating psychosocial effects for adolescents, the impact of which can last through adulthood.6,17 There are indications that when obesity is limited to childhood, its adverse psychosocial impact might be minimized,6 but without radical intervention, the chances that adolescent morbid obesity will continue into adulthood are almost 100%.18

Surgery is the most, and perhaps only, effective means of long-term weight loss.19 Adolescent bariatric surgery (ABS) is a relatively new subspecialty, and it is not without controversy. Nonetheless, the few studies empirically examining the psychosocial outcomes of ABS have generally supported anecdotal observations of improved psychological functioning and quality of life (QOL).20,21

This article provides an overview of the psychological and psychosocial consequences experienced by morbidly obese adolescents. Anecdotal observations, retrospective surveys, and prospective studies documented in the literature delineate the changes that typically follow ABS. Indicators of poor adjustment following surgery are described. Finally, recommendations for future studies are provided.

 

The Morbidly Obese Adolescent

For the 4% of adolescents who are morbidly obese (body mass index [BMI] >40), the medical and psychosocial consequences of obesity increase in a dose-dependent fashion with the severity of obesity.4,22,23 With BMIs as high as 105,24 morbidly obese adolescents seeking ABS can suffer from multiple, severe comorbidities,25,26 including congestive heart failure and pulmonary hypertension.27 Socially, they tend to be marginalized; they are unlikely to have a best friend or reciprocal friendships, and individuals who befriend them are more likely to be unpopular.23 When weight-related teasing occurs from multiple sources, which is often the case with extreme cases of obesity, there is a high prevalence of emotional problems, including low self-esteem, body dissatisfaction, depression, and anxiety.28,29 Many morbidly obese adolescents prematurely terminate their schooling or are home-schooled in order to avoid torment from their peers.19,30-32 Reports of passive suicidal ideation are documented in the literature.30

Treatment for pediatric obesity include behavioral, pharmaceutical, and surgical options.33 However, nonsurgical treatments result in relatively negligible weight loss that is typically regained.34-36 Repeated failures at weight loss are demoralizing to the adolescent and have been related to “severe psychological problems” and social withdraw anecdotally.30 The 1991 National Institute of Health Consensus Conference on Obesity Surgery37 sanctioned bariatric surgery as the most effective strategy for long-term weight loss and maintenance for severely obese adults. However, the lack of longitudinal, prospective studies with adolescent populations prevented the panel from endorsing it for youths. Nonetheless, there is a growing national demand for ABS with the number of procedures increasing more than five-fold from 1997–2003.38

 

The Psychological Outcomes of Bariatric Surgery

Although the morbidity and mortality associated with morbid obesity are startling, psychological distress, both internally and externally imposed, is likely the most pervasive problem experienced by morbidly obese adolescents.39 Experts recommend early surgical intervention in order to minimize the emotional as well as physical consequences of morbid obesity.18,20,22,24,25,27,30-32,34,40-63

 

Comorbid Psychopathology

Psychiatric symptoms are frequently described in samples of morbidly obese adolescents20,21,54,58,64-67 and are one of the most common comorbidities in adolescents presenting for ABS.58 Detecting the presence of pre-existing psychiatric symptoms is important because of speculation in adult literature that suggests an undiagnosed, pre-existing psychiatric disorder is one reason for procedural reversals.68 At least one adolescent study described two instances of “psychologic intolerance” resulting in gastric band removals.64 Additionally, knowing the frequency, severity, and duration of psychiatric symptoms preceding ABS is critical to interpreting post-operative symptoms. Nevertheless, numerous descriptions of both pre- and post-surgical psychological functioning are anecdotal, nonspecific, or vaguely referenced. There have been few empirical examinations addressing whether the severity of symptoms experienced by morbidly obese adolescents seeking ABS actually meets clinical criteria for disorder.

Depending on the method of assessment, US data show a lifetime prevalence of Axis I psychiatric disorders in ≤88% of adolescent patients seeking surgery.21,65 Research indicates that mood, anxiety, disruptive behavior, and eating disorders are the most common psychiatric comorbidities experienced by these patients. In studies where psychiatric comorbidities are listed, mood disorders have been reported in up to 68% of patients21,65 but generally occur in approximately 33% to 150% of samples.20,21,26,67 Lifetime history of anxiety disorders occurs in approximately 16% of samples.65 Reports of disruptive behavior disorders, including attention deficit hyperactivity disorder and oppositional defiant disorder, occur in ≤36% of adolescent patients.21,43,65 Eating disorders, most commonly binge eating disorder, have been reported in ≤13% of adolescent cases.21,65

Anecdotally, ABS resolves or improves the psychiatric symptoms of obese adolescents.69,70 At 1-year follow up, patients appear “brighter, more alert and more outgoing.”70 In a restrospective survey conducted at 6-year follow up, 85% of patients reported they were in good spirits “daily” or “almost daily,” which was more often than they recalled prior to surgery.31 Prospective, empirical data comparing pre- and post-surgical rates of psychiatric symptoms corroborate anecdotal observations and retrospectively collected data. In a longitudinal, prospective study,20 30% of pre-surgical adolescent patients had clinically significant depressive symptoms in the moderately severe range, as measured by the Beck Depression Inventory, Second Edition (BDI-II). Follow-up data collected at 3-month intervals demonstrated progressive symptom resolution. At 9-months follow up, there was a statistically significant, 22-point decrease in BDI-II scores among those who had been clinically depressed. No patients at follow up had clinically significant symptoms.

To varying extents, weight-loss success might impact resolution of mood and anxiety symptoms. In a 4-year follow up study with a 20% attrition rate and a 63% failure rate among remaining participants, 88% of the follow-up sample had elevated rates of depression and 50% were socially anxious.71 Although lack of pre-surgical data makes interpretation of these results difficult, it is speculated that the poor weight- loss outcome perpetuated or even aggravated pre-existing psychiatric symptoms.

 

Body Image

Soper and colleagues72 noted that morbidly obese adolescents view themselves as “huge, grotesque creatures.” For many, their self-disparaging thoughts are reinforced by their amorphous clothing39 and by the social discrimination they endure.73 Negative body image can be resistant to treatment72 and can lead to self-imposed isolation and depression.74 Morbidly obese adolescents have reported feeling more comfortable interacting with cyber-friends, preventing the possibility of their being judged on appearance.21

Reports of enhanced body image following weight-loss surgery have been reported in the ABS literature.24,25 In a 6-year, retrospective follow-up study, 82% of patients felt attractive and 74% felt less embarrassed about their appearance when in public, whereas virtually all had felt unattractive before undergoing surgery.31 There are indications, however, that poor body image persists but changes in focus. In one retrospective survey, surgical scarring and loose skin resulting from massive, rapid weight loss were sited by 20% of patients as the worst aspects of their bariatric experience.31 Complaints of scarring have decreased in recent years given the advent of laparoscopic procedures. However, adolescent patients have continued to site severe skin redundance as a source of embarrassment both in public places (eg, wearing tank tops or bathing suits) and in romantic relationships.18 To date, there have been no prospective studies that include outcome data regarding body image of adolescent patients.

 

Quality of Life

Morbidly obese adolescents report innumerable ways in which weight impacts their lives (Table 2). Health-related QOL is a multidimensional construct that describes ways in which symptoms of a disease and its comorbidities affect emotional, physical, social, and overall well-being and life satisfaction.75,76 Studies have consistently shown that across domains, obese adolescents’ QOL is below that of healthy adolescents’20,21,67 and is about equivalent to that of a child diagnosed with cancer.77 The desire to improve their poor QOL is a primary motivation for adolescents seeking ABS.30

 

Retrospective follow-up assessments with adolescent patients reveal positive changes to QOL, including improved self-esteem, school performance, increased socialization, and greater activity level.18,24,25,27,30,32,39,40,46,56,60,66,69,72 At a 3-year telephone follow up of 11 adolescent patients, 93% reported an improvement in physical activity, and 72% reported improved social life and self-esteem.63 In another survey,46 12 adolescent patients at 5-year follow up reported excellent academic and occupational functioning. Ninety-two percent reported improvement in overall health and greater social involvement with peers. Likewise, at 6-year follow up, 41% of patients retrospectively reported that the best surgical outcome was their increased self-esteem.31 A gross measure of QOL, the 5-item Moorehead-Ardelt questionnaire, has also consistently shown positive post-surgical ratings of social contact, school functioning, and physical activity.26,60

Improvements in prospectively assessed QOL have also been demonstrated. At 1-year follow-up,49 adolescents demonstrated significant improvements in social, familial, and academic functioning, as determined via clinical ratings of Global Assessment of Functioning.21 Clinical impressions were corroborated by the 36-item short form health survey, a commonly used self-report questionnaire measuring QOL across eight domains. Compared with pre-surgical ratings, patients reported improvements in social functioning, physical functioning, role limitations due to physical health and emotional problems, bodily pain, general health perceptions, vitality, and mental health functioning.21 Benefits were seen regardless of initial BMI severity, extent of weight loss, gender, and age (ie, younger versus older adolescents).

Similar trends were seen in a longitudinal study assessing overall QOL at 3-month intervals using the PedsQL. Although 80% of adolescent patient’s scores were in the abnormal range before surgery, scores had improved enough to be equivalent to those of healthy children 6 months after surgery. Although patients’ QOL scores declined slightly after 3 months, scores were still markedly higher than those before weight loss.

 

Indicators of Poor Post-surgical Adjustment

In clinical practice, a minority of follow-up patients have reported engaging in high risk behaviors, including drug use, gang involvement, and unsafe sexual practices. It is possible that some patients who undergo ABS are more prone to impulsive, risk-taking behaviors than typical adolescents.78,79 However, there are also concerns that their unsafe practices could reflect poor adjustment to post-surgical psychosocial changes. After years of social isolation and rejection, post-surgical adolescents typically experience increased social interactions. In their rush to develop friendships, some might be particularly vulnerable to negative peer influences. There is also concern that adolescents who previously used food to quell negative emotions might turn to drugs after ABS restricts their food intake.

At least one case study illustrated new onset of stimulant abuse. Dutta and colleagues80 described a 17-year-old female with a pre-surgical history of peer rejection and depressed mood, but with no prior history of drug use. Within 7 months of surgery, she had become acquainted with a known drug user and was smoking methamphetamine twice a day. The study cautioned that the appetite suppression qualities of stimulants, including methamphetamine, might make them particularly attractive to individuals with weight concerns. A second study, reporting on the long-term follow up of jejunoileal bypass, incidentally noted that one of their mortalities was a female adolescent who died 16 months post surgery as a result of drug and alcohol abuse.32 Although onset of substance abuse was not noted, pre-existing substance use is routinely an exclusionary criteria for ABS.19 Therefore, it is likely that drug use began following weight loss.

Similarly, unplanned pregnancies following ABS have been reported in the literature.39,53,81 In the most compelling account, a retrospective chart review of 47 adolescent Roux-en-Y gastic bypass (RYGB) patients documented seven unplanned pregnancies among six single, white females.81 The pregnancy rate of 12.8% was noted to be almost double the national average of 6.5% for the same demographic. Of note, all six patients had a pre-existing history of depression and two had comorbid anxiety. Changes in socialization, psychiatric functioning, and risk-taking tendencies might have placed these teenagers at greater risk for pregnancy. Reports that conception occurred within several weeks of the point of patients’ greatest weight loss could suggest that increased sexual attention played a role in the pregnancy. If the girls experienced irregular menstrual cycles secondary to obesity, it is possible that they thought they were infertile and dismissed the need for contraception. A third possibility is that the girls used oral contraception that was poorly absorbed because of the RYGB.32 In addition to the usual concerns regarding adolescent pregnancies, there is the added risk with bariatric patients that nutritional deficiencies may result in harm to the fetus.81 It is important to underscore the use of contraception in adolescent weight-loss patients.

 

Psychological Benefits Occur with Relative Weight Loss

Though numerous adolescent patients’ BMIs remain in the obese range at follow up,27,44,46,56,60,63,64 psychological benefits still present. For example, in Holterman and colleagues’20 sample, clinically significant reduction of depressive symptoms was seen although 50% of patients remained morbidly obese. It appears that the relative improvement in weight has psychological benefits even when patients remain overweight by normative standards. Some studies have reported that when patients have regained weight, they continue to report psychological gains.39,56 However, adult literature has demonstrated that with time, there is a decay of psychological benefits.82,83 One explanation is that as the initial social reinforcement for weight loss wanes, attention is refocused on aspects of life that failed to meet pre-surgical expectations. In almost all cases, however, post-surgical functioning is still improved compared to pre-surgical status. With the exception of the slight decrease in QOL ratings seen in one study,20 no ABS studies have systematically examined this issue. Given reports that at least some degree of weight regain is common31,34,56,84 and that morbidly obese adolescents have previously been demoralized by previous failed attempts at weight loss,30 it is possible that weight regain could result in psychological distress.

 

Conclusion

Current ABS studies have demonstrated the efficacy and safety of the surgical procedures. However, the investigation of psychosocial impact has been secondary in comparison.84 Research findings to date have been limited by small sample sizes, retrospective and cross-sectional designs, and failure to use standardized measures both pre-operatively and at follow up.18,24,27,40,42,44-46,50,54,55,64,70,84 Moving forward, it will be important to conduct prospective, longitudinal studies focusing on psychosocial outcomes and using multivariate analyses to examine various interaction effects. Given the existing literature on ABS, the roles of gender, chosen surgical procedure, BMI severity, percentage of excess weight loss, social status, family background, and mental health will be particularly intriguing. PP

 

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80.    Dutta S, Morton J, Shepard E, et al. Methamphetamine use following bariatric surgery in an adolescent. Obes Surg. 2006;16(6):780-782.
81.    Roehrig HR, Xanthakos SA, Sweeney J, Zeller MH, Inge TH. Pregnancy after gastric bypass surgery in adolescents. Obes Surg. 2007;17(7):873-877.
82.    Wadden TA, Sarwer DB, Womble LG, Foster GD, McGuckin BG, Schimmel A. Psychosocial aspects of obesity and obesity surgery. Surg Clin North Am. 2001;81(5):1001-1024.
83.    Waters GS, Pories WJ, Swanson MS, Meelhein HD, Flickinger EG, May HJ. Long-term studies of mental health after the Greenville gastric bypass operation for morbid obesity. Am J Surg. 1991;161:154-158.
84.    Dillard BE 3rd, Gorodner V, Galvani C, et al. Initial experience with the adjustable gastric band in morbidly obese US adolescents and recommendations for further investigation. J Pediatr Gastroenterol Nutr. 2007;45(2):240-246.

 

Dr. Luo is associate clinical professor in the Department of Psychiatry and Biobehavioral Sciences at the University of California in Los Angeles; past president of the American Association for Technology in Psychiatry (AATP) in New York City; and Gores Informatics Advocacy chair at the AATP.

Disclosure: Dr. Luo is consultant to S.M.A.R.T. Link Medical, Inc., on the speaker’s bureau of Epocrates, and on the advisory board of Spyglass Consulting.

 


 

 

The ultramobile personal computer (UMPC) has not yet had the success imagined by its designers. Its small form factor, a screen from 4–7 inches diagonal, and weight of <2 pounds,  make it more portable than a laptop. However, the first versions were underpowered with a slow central processing unit (CPU), which contributed to the UMPC’s lack of commercial success in today’s marketplace. The new Origami Experience 2.0 specification by Microsoft1 will hopefully change that experience with faster CPUs, more memory, and Windows Vista. Until that time, there are numerous other products that fill the void for the new mobile office.

 

Products

Apple Computer’s iPhone2 has been extremely popular in the United States despite its exclusive sales contract with ATT Wireless. In fact, a cottage industry has emerged that provides various methods to bypass the security so that the device can be used on other wireless provider networks.3 The iPhone is an extremely capable device, with Internet browsing, video and audio playback, and e-mail; however, it is limited to these capabilities. The new third-generation data service version expands the iPhone’s repertoire with faster third-generation wireless technology, global positioning satellite (GPS), enterprise features, and now, third-party applications. The enterprise capability is significant in that support for Microsoft Exchange Activesync provides for push e-mail, calendar, and contacts from the Microsoft Exchange server, a popular server in numerous corporate environments. This feature positions the iPhone as a rival to the Research in Motion’s extremely popular Blackberry devices. With the release of the iPhone SDK (software development kit), Apple is now encouraging other developers to create applications for the iPhone such as Epocrates Rx,4 which was previously only available to iPhone users via the Safari Web browser. Applications such as a word processor or spreadsheet program—eg, iWorks5 or Documents-to-Go6 on the iPhone—are not yet in development but may be coming soon. A current alternative is to use the Glide Operating System,7 which is a Web browser-based application suite that runs on multiple operating systems such as Blackberry, Windows Mobile, Mac, Windows, Palm, and Linux. Glide is not really an operating system but a specially written Adobe Flash code to create, edit, and read various Microsoft Office compatible files. The problem with using the iPhone as a mobile office is that there is no Bluetooth keyboard for it since the iPhone’s Bluetooth is designed only to connect to Bluetooth headsets.

The RIM Blackberry is another computing alternative for the mobile office. When these devices are connected to the RIM Enterprise server, which is typically linked to the Microsoft Exchange Server for push e-mail and calendar, e-mail attachments, such as Microsoft Word and Excel, can be opened for viewing. Adobe Portable Document Format files are also viewable on the Blackberry as an image to see the true layout, or just the text, which is much more readable. As with the iPhone, Web-based office suites such as Google Docs or Thinkfree Office work for viewing but not editing. One reason to use these online document editing services is that these documents can be left on the server for editing at any Internet-connected computer with a Web browser or viewed in the field on a mobile phone that has a signal. If editing a Microsoft Office file is desired on the Blackberry, DataViz Documents-To-Go is available for the Blackberry system, which can edit the native file without any portable file conversion. Many Blackberry devices have a small thumb-based keyboard, which is not ideal for lengthy typing. For some users, the small screen is not prohibitive for document editing or viewing, which makes pairing it with the iGo Stowaway Ultraslim Bluetooth Keyboard8 an option for a truly mobile office. Presently, the Blackberry devices rely only on the mobile phone service for Internet access; however, the new Blackberry Bold9 will offer the ability to utilize WiFi networks in addition to the wireless carrier data service. This feature allows the Blackberry to compete with the iPhone as a device that works on either wireless data network, which provides flexibility in hospital settings where mobile phone signals tend to be severely attenuated.

Although many of the document-editing options described above do work, the Web-based document services occasionally do not save properly, the synchronization may not work between the Internet storage and the local computer, or the service will just crash. DataViz’s Documents-To-Go works well on the Palm and Blackberry platform, but for complete peace of mind, it may be best for some to just stick to Microsoft. Fortunately, there are numerous manufacturers of Windows Mobile smartphone devices that offer Word Mobile, Excel Mobile, and PowerPoint Mobile since it is included in the operating system. Sony Ericsson Xperia X1 is poised to shakeup the crowded Windows Mobile smartphone market with its 3-inch diagonal, 800×480 resolution screen and slide-out built-in keyboard in addition to its multi-media–rich capabilities.10

If the screen and keyboard are too small for extensive document or e-mail reading and editing, Celio’s Redfly Mobile Companion may be the perfect solution.11 This product provides an 8-inch diagonal wide screen with 800×480 resolution, full-size keyboard, and a touchpad mouse to extend the capabilities of a Windows Mobile device. After the Redfly interface driver is installed on the smartphone, the device connects either via Bluetooth or universal serial bus (USB). One advantage of carrying this 2-pound mobile companion, besides the larger screen and keyboard, is that it will charge the smartphone in addition to allowing USB flash drives to be connected for more storage or file access. At present, this peripheral is only compatible for Windows Mobile devices listed at www.celiocorp.com/smartphone,12 but they anticipate that Blackberry, Motorola, and Nokia drivers will be developed in the future.

HTC also makes a Windows Mobile smartphone called the Touch Pro, which is in direct competition with the Sony Xperia X1.13 This device has a slightly smaller 2.8-inch diagonal screen and a slider keyboard. However, HTC’s other products, the Advantage14 and Shift15 mobile computers, are blurring the boundary between smartphone and UMPC. The HTC Advantage has a 5-inch diagonal video graphics array touch screen with a detachable keyboard and runs on Windows Mobile 6 Professional operating system. It has integrated Wi-Fi, Bluetooth, GPS, and 3G, which gives it great flexibility to connect for e-mail and Web browsing. Although it is quite portable, it is bulkier than many of the devices described so far. Similarly, the HTC Shift is more of a laptop with a 7-inch, 800×480 display, Intel processor, and 40 or 60 GB hard disk running the Windows Vista Business operating system. The keyboard slides out and the display tilts backwards for easier viewing. One significant advantage of this device is the SnapVue operating system, which is a second operating system that gives instant access to e-mail, calendar, and weather.

If deciding between an UMPC, smartphones, and ultra-portable laptops such as the HTC Shift and OQO model 02 is not confusing and difficult enough, there is another category of mobile devices called the Mobile Internet Device (MID). Intel has created a marketing and branding infrastructure around its Centrino Atom processor, which powers many of these devices.16 The MID is supposed to be smaller with 4–6-inch displays, and most run on optimized versions of Linux. Moblin.org17 is an open source community for sharing software, ideas, projects, codes, and applications to devices running Linux on the Intel Atom processor. At present, there are no planned releases of an MID based on the Intel Atom processor, although many are in development.

One company already ahead in the MID arena is Nokia. It has developed the N800 and N810 mobile Internet devices18 on a Texas Instruments processor and runs Maemo,19 another open-source development site for Internet tablets. Portability and ease of use are its key features, with a 4.13-inch screen at 800×480 pixels and weight of <8 ounces. These devices only have WiFi and Bluetooth connection, 2 GB of internal memory, and support for up to 8 GB miniSD and microSD memory cards. The main difference between the N800 and N810 models is the slide-out keyboard on the N810. These devices do not have the capabilities as of yet to run office application suites such as Open Office,20 but many are in development. Since Adobe Flash 9 is not yet ready for Maemo,21 the Glide system will not work.

 

Conclusion

Numerous devices purport to bring e-mail, calendar, Microsoft Word, Microsoft Excel, and Microsoft PowerPoint into the mobile age. Just as there are numerous antidepressants with different mechanisms of action, one mobile device does not fit all of the mobile computing needs of the health professional. Some users will want the larger screens and keyboards offered in the bigger devices, while others will crave the portability of smartphones and MIDs. Even laptops have entered the market with subnotebooks such as the MSI Wind22 and Asus EEE PC,23 both of which run the Linux operating system for better power management and lower cost of ownership. Despite the uncertainty concerning which operating system or which form-factor device will serve the mobile office needs, a laptop in the pocket is on its way.24 PP

 

References

1.    Ultra Mobile PC with Origami Experience 2.0. Available at: www.microsoft.com/windows/products/winfamily/umpc/default.mspx. Accessed June 30, 2008.
2.    iPhone. Available at: www.apple.com/iphone. Accessed June 30, 2008.
3.    Code to Unlock iPhone Cracked. Available at: www.cnn.com/2007/TECH/09/01/apple.iphone/. Accessed June 30, 2008.
4.    Epocrates on iPhone. Available at: www.epocrates.com/iphone/compatibility/. Accessed June 30, 2008.
5.    Apple iWork. Available at: www.apple.com/iwork. Accessed June 30, 2008.
6.    DataViz Documents to Go. Available at: www.dataviz.com. Accessed June 30, 2008.
7.    Glide OS. Available at: www.glideos.com. Accessed June 30, 2008.
8.    iGo Stowaway Keyboard. Available at: http://corporate.igo.com/product_details.aspx?id=16. Accessed July 1, 2008.
9.    Blackberry Bold. Available at: www.blackberry.com/select/blackberrybold/. Accessed July 1, 2008.
10.    Sony Experia X1. Available at: www.sonyericsson.com/x1/. Accessed July 1, 2008.
11.    Celio Redfly Mobile Companion. Available at: http://celiocorp.com/products.php. Accessed July 1, 2008.
12.    REDFLY Tested Smartphones. Available at: www.celiocorp.com/smartphone. Accessed July 3, 2008.
13.    HTC Touch Pro. Available at: www.htc.com/www/product.aspx?id=49518. Accessed July 1, 2008.
14.    HTC Advantage. Available at: www.htc.com/www/product.aspx?id=436. Accessed July 1, 2008.
15.    HTC Shift. Available at: www.htc.com/www/product.aspx?id=596. Accessed July 1, 2008.
16.    Intel. Mobile Internet Devices. Available at: www.intel.com/products/mid/. Accessed July 2, 2008.
17.    Moblin.org. Available at: www.moblin.org/community/mid/. Accessed July 2, 2008.
18.    Nokia N810 Internet Tablet. Available at: www.nokiausa.com/A4626059. Accessed July 2, 2008.
19.    Maemo. Available at: www.maemo.org. Accessed July 2, 2008.
20.    Open Office. Available at: www.openoffice.org. Accessed July 2, 2008.
21.    Flash 9 Coming to Maemo? Available at: www.internettablettalk.com/2007/01/17/flash-9-coming-to-maemo/. Accessed July 2, 2008.
22.    MSI Wind. Available at: www.msimobile.com/nblist.aspx?series=u. Accessed July 2, 2008.
23.    ASUS EEE PC. Available at: http://eeepc.asus.com/us/index.htm. Accessed July 2, 2008.
24.    Machlis S. Coming soon: a laptop in your pocket. Computerworld. Available at: www.computerworld.com/action/article.do?command=viewArticleBasic&articleId=9103538&source=NLT_HW&nlid=51. Accessed July 2, 2008.

Articles

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Christine Ren Fielding, MD, and George Fielding, MD

Primary Psychiatry. 2008;15(8):40-41

 

Drs. C.R. Fielding and G. Fielding are associate professors of surgery at New York University School of Medicine in New York City.

Disclosure: Dr. C.R. Fielding is consultant to ExploraMed and the Surgical Review Committee; on the advisory boards of Allergan Health and Ethicon Endosurgery; is on the speaker’s bureau of Allergan Health; and receives grant support from Allergan Health. Dr. G. Fielding is consultant to ExploraMed; is on the advisory board and speaker’s bureau of Allergan Health; and receives grant support from Allergan Health.

Please direct all correspondence to: Christine Ren-Fielding, MD, Associate Professor, School of Medicine Surgery FGP General, NYU Medical Center, 530 First Ave, 10 S, New York, NY 10016; Tel: 212-263-3166; Fax: 212-263-3757; E-mail: Christine.ren@med.nyu.edu.

 


 

Obesity is about to surpass cigarette smoking as the number one preventable cause of death in the United States. In the year 2000, data showed that 435,000 Americans died from cigarette smoke and 400,000 from obesity.1 This represents 18.1% and 16.6%, respectively, of all deaths in the US. Greater than 33% of US adults (>72 million people) were obese in 2005–2006.2,3 Obesity in children and adolescents is also on the rise and is associated with increased morbidity and mortality in adult life.

The degree of obesity is estimated by body mass index (BMI), which is calculated as weight divided by the square of height and is reported in the metric units of kg/m2. If pounds and inches are used, the following formula can be used to convert from English to metric units: BMI=[weight (lbs)/[height (inches)]2]x703. A BMI of 18–25 is considered healthy weight, BMI of >25–30 is considered overweight, BMI of >30–40 is considered obese, and BMI of >40 is morbidly obese.

The World Health Organization has listed obesity as an epidemic.4 Being obese is not the problem; rather, the problem is the diseases that flow from it, ie, diabetes, sleep apnea, hypertension, elevated cholesterol, arthritis, cancer, and depression. The current epidemic of diabetes is already of plague-like proportions. A new diabetic is diagnosed every 10 minutes in the US. One in every three newly diagnosed diabetics is a teenager. The implications are terrifying. By 2020, the National Institutes of Health (NIH) believes 20% of all health dollars will be spent on diabetes. With few exceptions, diabetes comes from obesity.

There are individual as well as national implications for obesity. A recent publication in the Journal of the American Medical Association showed that a 45-year-old man with a BMI of 45 who smokes will lose 13 years of his life.5 If he does not smoke, he will lose 8 years of life. Furthermore, his life will be mired in disease. A BMI of 45 equates to a person who is 5’11” tall and weighs 320 lbs. The average BMI in most bariatric practices is 47 kg/m2. There are literally millions of people of this size in the US.

The medical treatment of obesity is relatively ineffective.5-9 Optimal application of a program of best practice for healthy eating, exercise, drug therapy, and psychological intervention might lead to a weight loss of up to 20 lbs, if applied continuously. Long-term application of the program is rarely achieved. Only 2% of patients can keep 50 lbs off for 1 year, and 95% of dieters regain all lost weight with an incremental increase over their base weight. The NIH recognized this in 1991 when it endorsed bariatric surgery for the morbidly obese.10 Specifically, a BMI of ≥40 is an indication for surgery. The BMI can be lowered to 35 if the individual has at least one obesity-related illness, such as diabetes.

Bariatric surgery (surgery for severe obesity) offers a surgeon the opportunity to cure disease and to prevent further diseases, possibly for the first time. Surgery has been shown to be a highly effective long-term intervention for obesity,11 and bariatric procedures have been performed with greatly increasing frequency in recent years. The two most frequently performed bariatric surgeries in the US, Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable gastric banding (LAGB) procedures, both lead to rapid and dramatic weight loss. Bariatric surgery typically results in significant improvement or amelioration of the debilitating medical comorbidities of obesity such as Type II diabetes (86% improvement), obstructive sleep apnea (84% improvement), hypercholesterolemia (>70% improvement), and hypertension (79% improvement).11

LAGB is a restrictive operation which relies on decreased amount of intake as the mechanism for weight loss. It involves the surgical implantation of an inflatable silicone band around the uppermost part of the stomach, which is tightened in the office based on individual weight loss and appetite. This operation has minimal nutritional sequelae.

RYGB is also a restrictive operation, but it includes a component of nutrient malabsorption. The top of the stomach is cut and separated from the rest of the  stomach in order to create a new tiny stomach pouch. What is originally the size of a football, now has the capacity of a golfball. This new tiny pouch is attached to the intestine farther in the digestive tract, allowing for food to be rerouted away from the original stomach and part of the intestine. This results in appetite suppression, early satiety, and decreased absorption of nutrients. Vitamin supplements are imperative for these patients. Both operations can be performed laparoscopically with minimal surgical complication. However, the tenets of nutrition and behavior modification are critical for optimal weight-loss outcome.

Approximately 250,000 bariatric operations were performed in 2007 (American Society for Metabolic and Bariatric Surgery, personal communication, June 21, 2008); this is a reflection of the growing obesity problem. Because bariatric surgery is becoming much more prevalent, healthcare professionals of all disciplines are increasingly likely to encounter bariatric patients in their clinical practices. Therefore, it is important that even clinicians who do not specialize in working with this population become knowledgeable about surgery and the common postoperative experiences that patients face, in order to ensure the provision of appropriate care and referrals.

Warren L. Huberman, PhD, begins this issue by discussing the role of the mental health professional in both the preoperative and postoperative bariatric surgery patient setting, drawing from his personal experience of >5,000 patients. Psychosocial changes occur after bariatric surgery, in both positive and negative terms. David B. Sarwer, PhD, and colleagues discuss what these changes may be and what the mental health professional can expect. Stephanie Sogg, PhD, and Mark J. Gorman, PhD, look at the interpersonal changes that occur after bariatric surgery; these involve relationships and intimacy. This article will help the mental health professional recognize and address them. Andrea D. Vazzana, PhD, discusses the destructive effects of obesity on the adolescent population with the subsequent positive, and potentially negative, mental health outcomes after bariatric surgery. Finally, Susan F. Franks, PhD, and Kathryn A. Kaiser, BS, provide a comprehensive review of the literature regarding predictive factors in bariatric surgery outcomes.

This issue of Primary Psychiatry assesses the psychological impact of weight-loss surgery, possibly even more important to the patient than the medical benefits. As bariatric surgery continues to become the mainstream treatment for severe obesity, these psychological issues will be met by all doctors caring for their obese patients. PP

 

References

1.    Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006;295(13):1549-1555.
2.    Obesity among adults in the United States–no statistically significant change since 2003-2004. Data Brief Number 1, November 2007. 8 pp.  Available at: www.cdc.gov/nchs/pressroom/07newsreleases/obesity.htm. Accessed July 15, 2008.
3.    Baskin ML, Ard J, Franklin F, Allison DB. Prevalence of obesity in the United States. Obes Rev. 2005;6(1):5-7.
4.    WHO Consultation on Obesity. Obesity: Preventing and Managing The Global Epidemic: Report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 2004.
5.    Fontaine KR, Redden DT, Wang C, Westfall AO, Allison DB. Years of life lost due to obesity. JAMA. 2003;289(2):187-193.
6    Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.
7.    Tuomilehto J, Lindstrom J, Eriksson JG, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343-1350.
8.    Stern L, Iqbal N, Seshadri P, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Ann Intern Med. 2004;140(10):778-785.
9.    Foster GD, Wyatt HR, Hill JO, et al. A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348(21):2082-2090.
10.    Gastrointestinal surgery for severe obesity: National Institutes of Health Consensus Development Conference Statement. Am J Clin Nutr. 1992;55(2 suppl):615S-619S.
11. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724-1737.