Dr. Weiss is head of the Provincial ADHD Program and clinical professor at the University of British Columbia Children’s and Women’s Health Centre in Vancouver.

Disclosure: Dr. Weiss is a consultant to and receives grant support from Eli Lilly, Janssen, Purdue, and Shire. She also receives grant support from the Canadian Institutes of Health Research.

Please direct all correspondence to: Margaret D Weiss MD PhD, Head, Provincial ADHD Program, Clinical Professor, University of British Columbia, Children’s and Women’s Health Centre, Box 178 , 4500 Oak St, Vancouver, BC V7T 2Y2; Tel: 604-875-2010; Fax: 604-875-2099; E-mail: mweiss@cw.bc.ca.


 

All assessments in child psychiatry involve evaluation of particular areas that are not typical in an adult assessment. These include a detailed school history, developmental history, a family interview, and collateral information obtained usually by rating scales from teachers and parents. In certain aspects of adult psychiatry some of these child procedures may also serve to augment the assessment process. Collateral information may be useful in assessment of a patient without insight, such as a patient with hypomania. Rating scales can be useful in identification of severity and follow up of improvement. Broad-based rating scales can be used to assure identification of diagnoses that might be missed by the clinician, or that the patient is reluctant to discuss.

Just as there are procedures that are unique to child psychiatry that may be of benefit to adult psychiatry, there are procedures unique to assessment of attention-deficit/hyperactivity disorder (ADHD) for patients of all ages that may be useful to general child or adult psychiatrists. I will identify the modifications to the assessment process now in place in our Provincial ADHD Program which I think may be of use to those in general practice seeing patients with ADHD, or even to practitioners who are seeing patients with other diagnoses where the same type of issues arise.

In order to improve the efficiency of the assessment process and optimize the time available for discussion of psychosocial care we need to know quickly and as easily as possible Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition1 diagnoses that might have been missed, are comorbid, or represent differential diagnoses. We also need to identify those diagnoses that are apparent to different observers and in different settings. The Kiddie-Schedule for Affective Disorders and Schizophrenia (KSADS) has been used clinically for diagnoses, but the reality of the constrictions on the clinical time we have available is that this is expensive and limited to information from the family. The KSADS and other diagnostic interviews were designed for research. However, the objective of such interviews is as germane in practice as in research. For this reason, the Canadian ADHD Resource Alliance2 has developed a DSM-IV checklist that is completed by the patient and a collateral informant prior to interview. The advantage of this interview is not a substitute to the mental status, but to serve as a guide to the mental status and to assure the clinician remembers what the DSM criteria are as well as to identify important patient/collateral differences.

Since the emergence of the DSM, the diagnostic process has focused heavily on symptoms, and diagnostic criteria. However, patients do not typically present with the chief complaint that they have a DSM disorder. More often, they present with a problem in life functioning where they have difficulty meeting the new expectations of a developmental transition. While Axis V is meant to identify impairment, there is no description of what impairment is—whether it represents absolute impairment or impairment relative to potential—or the settings in which such impairment occurs. Nor on Axis V is there anything like the diagnostic criteria that bring interrater reliability and definition to Axis I.

The reality familiar to all clinicians is that there are patients who have significant diagnoses and function well and patients who have a vague mixture of symptoms from different diagnoses who are severely impaired. For this purpose, prior and post interview from the Weiss Functional Impairment Rating Scale for Self (WFIRS-S: adolescents or adults; Table 1) or WFIR for Parents (Table 2) examines impairment in each of the major domains. Like the Symptom Record, this can be reviewed, discussed with the patient, and used as a cross check on the interview. Within the busy service requirements of the ADHD clinic, psychiatrists do not have the luxury of psychologists to score complex scales. We use the simple rule of rating both symptoms and functional items that are of clinical significance by simply counting those items rated as 2 (pretty much) or 3 (very much) by the patient or informant. While simple, this is much like the Clinical Global Impression–Severity scale in that it gives a precise and clear characterization of the patient’s difficulties.

 

 

 

Some differentials that are more common in ADHD, and therefore a necessary part of the evaluation. However, while they may be more common, they are by no means unique to ADHD. An ADHD assessment requires an evaluation for learning disabilities, sleep, nutrition, bullying, family discipline, and parental frustration. as well as capacity for activities of daily living, school or work success and adaptations, and risk factors such as drug use, driving, or injuries. Evaluation of these differentials and risk factors by self and other report on the Symptom Record and the WFIRS assures that patients receive the clinical attention they deserve.

Perhaps the most important and most often missed aspect of psychiatric assessment is that we are trained to be pathology sensitive. However, from the patient’s point of view identification and reinforcement of strengths and successes sets a tone and models a positive experience. We know very little about what determines long-term outcome apart from obvious advantages such as income, personality, family support, and resilience. However, one aspect of possible prognostic signficance that is likely to be stable over time is the capacity to be compassionate and kind. For example, one of the most widely used child broadband rating scales in the public domain that is age and gender normed, the Strengths and Difficulties Questionnaire,3 has as one of its five subscales “prosocial skills.” Kindness may well be a stable characteristic that when assessed at any age represents a relative strength that can be drawn on to identify to the patient that whatever the symptomatology, her or she is “a good person.” Outcome is not only determined by what is disturbed, but also by what the patient does well. Are they empathic? Do they have a special passion for a skill they do well? Are they psychologically minded?

Apart from inclusion of the whole family, one aspect of child psychiatry that is unique and critical to ADHD is the developmental history. Has their been in utero exposure to nicotine, alcohol, or other drugs? Was their compromise to the newborn during delivery? What was the child’s early temperament? (Temperament tends to be relatively stable, and early memories are of interest.) Were there notable developmental delays, such as clumsiness, indicative of residual developmental coordination disorder? An assessment of ADHD in adults requires the same type of evaluation, since like all neuropsychiatric conditions grown up, early childhood history is critical to establishing a developmental onset of difficulty. Again, while these questions are critical to assessment of ADHD, they may identify early onset prognostic deficits relevant to all adult conditions.

When one asks a child if they have problems paying attention or whether they get into trouble, they often know the answer. When asked if the problem is small, medium, or large, their assessment is also not unlikely to match the results of systematic interview. The point is simple: in adult psychiatry we have the advantage that we interview the patient directly, but nonetheless we may fail to bring into the office those significant others who know the patient in a way he cannot know him or herself. In child psychiatry, we often focus our interview on parent and teacher information. However, the informant who remains critical to an ADHD assessment or any child assessment is the child. A child might say, “I am lazy.” “I only like recess because it is the only part of school that is not boring.” “I have no friends because I am bad.” Assuring that the child remains an important part of the interview provides clues to diagnosis, child insight, and functional impairment. It also tells the clinician the child’s own experience of the impact of his or her disorder on quality of life. Whether this is an assessment of an adult with ADHD and we decide to include the spouse, or an assessment of the child and we interview the caregivers and obtain information from the school, assessment of ADHD is a reminder to all psychiatry that collateral information often brings surprises. In adult psychiatry, where most patients are seen individually for 1 hour, the use of collateral scales has a major role to play that has been under utilized.

The Symptom Record completed by patient and collateral provides a simple, cost effective way to obtain a pathway into the key problems, and an assurance that we won’t miss disorders such as learning problems, sleep, or tics that might otherwise be missed. The Weiss Functional Impairment Rating Scales reminds us that patients came to the interview hoping to be able to do things or meet developmental milestones that have remained closed to them. It reminds the patient and the doctor that even when we get the diagnosis right, if we do not know the problem, the patient will not significantly progress.

ADHD is a neurodevelopmental condition which like many mental health disorders carries through the life cycle, presenting new difficulties as the patient faces new challenges. What we have to learn from assessment of ADHD in adults and children is that a developmental history, collateral information, and assessment of developmental cormorbidities such as sleep or learning have the possibility to deepen and create a better understanding for patients of all ages and all disorders.  PP

 

 

References

1.    Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
2.    CADDRA. The Canadian Attention Deficit Hyperactivity Disorder Resource Alliance. Available at: www.caddra.ca. Accessed April 12, 2010.
3.    SDQ. Information for researchers and professionals about the Strengths & Difficulties Questionnaires. Available at: www.sdqinfo.com. Accessed April 12, 2010.

 

Dr. Kennedy is professor in the Department of Psychiatry and Behavioral Sciences at Albert Einstein College of Medicine, and director of the Division of Geriatric Psychiatry at Montefiore Medical Center in the Bronx, New York.

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

Please direct all correspondence to: Gary J. Kennedy, MD, Director, Department of Geriatric Psychiatry, MMC, 111 East 210th St, Klau One, Bronx, NY 10467; Tel: 718-920-4236; Fax: 718-920-6538; E-mail: gjkennedy@msn.com.


 

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition,1 is scheduled for release in May 2013. In February 2010, the preliminary draft revisions to the current diagnostic criteria became available for review and comment. Although diagnostic biomarkers and neuropsychologic criteria for dementia have yet to emerge, there are conceptual advances evident in the proposed criteria which have substantial implications for treatment. What follows is a discussion of the proposed revisions to help readers who may want to submit comments during the review period.

The DSM-5 proposes four major changes2 for the cognitive disorders listed in the DSM-IV-TR 3 as delirium, dementia, and amnestic disorders. These include dropping the term “dementia” entirely, adding a new diagnostic category titled “minor neurocognitive disorder,” and explicitly categorizing the syndromes of psychosis and depression previously described for Alzheimer’s disease but not mentioned in the DSM-IV. 4 The fourth change is the provision of far greater detail, examples, and assessment techniques for the specific cognitive domains of impairment. Each change reflects advances in neuroscience, neuropsychology, and neuroimaging. However, the first three are also the result of a conceptual process that began more than a century ago.

 

Historic Background

Kraepelin assigned the name “Alzheimer’s disease” to Alzheimer’s initial case reports of marked cognitive deterioration associated with neurofibrillary tangles in 1907 and amyloid plaques in 1911.5 But “Alzheimer’s disease” does not appear in the DSM until the DSM-III.6 Controversy arose over whether Alzheimer’s findings were those of a genuine disease or of normal aging. In addition, there was no consensus about how to classify the illness if it indeed was a disease. In 1951, the United States Public Health Service established a work group to address difficulties perceived in the International Classification of Diseases, Sixth Edition (ICD-6).7 Among the shortcomings were ICD-6’s failure to include chronic brain syndromes (dementias) within the coding rubric of mental disorders along with neurotic and behavioral reactions such as anxiety and depression. This was incongruent with the DSM-I,8 which was published in 1952. In addition, many of the “psychoses associated with organic factors,” meaning dementias, were lumped into a category labeled “psychoses with other demonstrable etiology.”9

Debates about the terminology of cognitive disorders continued through the publication of the DSM-II 10 and the ICD-8.11 Terms such as “brain syndrome” as well as “organic psychoses” and various modifiers were proposed. The term “psychosis” was used to denote severity rather than the presence of hallucinations or delusions. What current practitioners might refer to as vascular dementia would have been classified in the DSM-II as “psychoses associated with organic brain syndromes with cerebral arteriosclerosis (293.0) or other cerebrovascular disturbance (293.1). “Psychoses not attributed to physical conditions” included schizophrenia and manic depressive illness.10 Uncertainty about where to place these conditions and how to describe them reflects their dual identities as both neurologic and psychiatric disorders. This duality is also reflected in the functional versus organic terminology now thought to be out of date as well as inaccurate. Captioning neurodegenerative disorders in which mental rather than motor or perceptual deficits predominate is a historic trend across the DSMs. By transforming the cognitive disorders of the DSM-IV into neurocognitive disorders, the DSM-5 acknowledges the neurologic aspect of the illness without ceding the diagnosis entirely to neurology or primary care. The dementias are mental disorders. Nonetheless, some states bar people with a diagnosis of dementia from receiving services at Medicaid-certified mental health clinics unless there is a specific diagnostic modifier denoting “depression” of “delusions,” or a concurrent major mental disorder such as major depressive disorder (MDD).12

 

Out with the Old, in with the New

Delirium, dementia, amnestic, and other cognitive disorders are subsumed in the DSM-5 under the category of “neurocognitive disorders.” Neurocognitive disorders, in contrast to neurodevelopmental disorders, are acquired and degenerative rather than inborn and apparent in childhood. The term was chosen in part to avoid the stigma associated with dementia when categorizing deficits among younger people with progressive cognitive decline associated with HIV or traumatic brain injury. Neurocognitive disorders are further divided into major and minor. The DSM-IV condition described as “age-related cognitive decline (ARCD)” appearing in “other conditions that may be a focus of clinical attention” would now appear under minor neurocognitive disorder in the DSM-5. This is a decided advance. Terms such as ARCD, cognitive impairment not dementia (CIND), mild cognitive impairment (MCI), amnestic MCI, and non-amnestic MCI—which have variable criteria but are often considered a prodrome of dementia—would now be listed as a minor neurocognitive disorder. More importantly, in contrast to those without detectable impairment, people with CIND exhibit both a greater prevalence of neuropsyschiatric symptoms such as depression as well as functional limitations.13

Minor neurocognitive disorder is analogous to minor depressive disorder, which appears in Appendix B of the DSM-IV along with subsyndromal depressive condition not elsewhere classified (CNEC). Indeed, subsyndromal depressive CNEC is further divided into prodromal depression and subsyndromal, and mixed subsyndromal anxiety-depressive disorder depending on duration, severity, or associated features, respectively. Both MCI and minor depression are similar in that they predict progression to either dementia or MDD. However, many people considered to have MCI or minor depression never develop a major mental illness. The certainty with which we can distinguish a symptom or performance profile which represents a genuine prodrome from periodic variability in cognitive performance or mood remains problematic. Nonetheless, identifying minor neurocognitive disorder as a DSM diagnosis reflects a growing consensus that MCI and CIND are too often the early manifestations of dementia. Additionally, not to have a “minor” diagnostic category would leave investigators and the public with the confusing terminology that followed in the wake of the DSM-IV.

 

Behavioral Disturbances Categorized

Behavioral disturbances of Alzheimer’s disease are prevalent and add excess disability for the patient and distress for caregivers. Community-based studies13-15 find agitation, apathy, depressed mood, delusions, and less frequently hallucinations to be the most common problems. In the DSM-II, the dementias were categorized as either psychotic or non-psychotic organic brain syndromes. Severity of impairment—not the presence of delusions or hallucinations—determined whether or not the disorder was of psychotic proportions. Hallucinations, delusions, and alterations in mood were considered part of the disorder but no modifying code or category was proposed. With the publication of the DSM-IV-TR, modifying codes had been added to reflect the presence or absence of behavioral disturbance.3 For vascular but not Alzheimer’s dementia, modifying codes included “with delirium,” “with delusions,” and “with depressed mood.” Two syndromes are proposed for the DSM-5,  but specifically for Alzheimer’s disease. The first is a depressive syndrome in which three symptoms of MDD must be present for a minimum of 2 weeks and cause disability or distress. The second is a syndrome of psychosis in which delusions or hallucinations have been present at least intermittently for a minimum of 1 month and cause disability or distress. Alternatively, other behavioral problems such as agitation, aggression, apathy, wandering, disinhibition, or circadian rhythm disturbance might be coded as a fifth digit across any of the neurocognitive disorders. However, with behavioral problems so prevalent and so distressing to caregivers, the work group is wise to flag these matters as requiring additional input. Behavioral disturbance modifiers are necessary in some states for Medicaid-certified mental health clinics to provide services to people with dementia.12
 

Cognitive Domains Mature

The DSM-IV identifies impairments in memory and learning plus one of the following—aphasia, apraxia, agnosia, or executive dysfunction—as criteria for dementia. Deficits must cause social disability to justify the diagnosis. The proposal for the DSM-5 includes domains for “complex attention, executive ability, learning and memory, language, visuoconstructional-perceptual ability, and social cognition.” Each item has a paragraph describing major and minor deficits as well as definitions of the domain and examples of assessment procedures. Equally important are descriptions of how impairment within the domain disrupts behavior and threatens independence. The work group remains uncertain about how to formally portray domain-specific deficits. However, it seems critical to tailor the caregiver approach and structure the environment to take advantage of capacities which are preserved and to compensate for those which are deficient. Achieving the right fit between strengths and vulnerabilities would presumably lessen the patient’s disability, reduce the caregiver’s burden, and minimize the occurrence of behavioral disturbances. This is likely to be the case for people with Alzheimer’s, Parkinson’s, and Lewy Body diseases but may be equally important for veterans of Iraq and Afghanistan returning home with traumatic brain injury. Given the disappointing results from pharmacotherapy for the behavioral disturbances of dementia, a more exacting description of domain-specific deficits could be a major public health advance.16
 

Conclusion

Changes proposed in the DSM-5 related to delirium and dementia highlight the clinical nature of these diagnostic categories. Objective criteria from neuropsychological, imaging, or laboratory assessments are mentioned but neither specified nor required to make the diagnosis. This is a reflection more on the marked variation in neurobiology and cognitive performance between individuals both healthy and otherwise rather than a lack of reliable measures of change within the individual.13,16 The distinction between major and minor neurocognitive disorders also reflects the intense scientific interest in identifying the prodrome for dementia. Given the frequency with which MCI and CIND progress to dementia, failure to include minor neurocognitive disorder would seem a major error. However laudable it may be to avoid the stigma associated with the term “dementia,” substituting “neurocognitve disorder” reminds one of bipolar I (manic) and bipolar II (depressed) of the DSM-IV, which replaced the DSM-II’s “manic depressive illness.” Nonetheless, changes in nomenclature matter. Addition of salient behavioral problems to the diagnostic code regardless of etiology seems clinically sound. The adoption of modifiers to capture even one specific domain of cognitive deficits may lead to improved behavioral approaches. There is bound to be debate about “minor neurocognitive disorder” and the abandonment of “dementia” just as there has been for autism and Asperger’s syndrome.19 However, the clinical utility of noting behavioral disturbance and domain-specific deficits is hard to deny.  PP
 

References

1. Diagnostic and Statistical Manual for Mental Disorders. 5th ed. Washington, DC: American Psychiatric Association; In press.
2. Neurocognitive Disorders Work Group: Jeste D, Blacker D, Blazer D, et al. Draft dated 7 January 2010. Available at: http://www.dsm5.org/ProposedRevisions/Pages/Delirium,Dementia,Amnestic,OtherCognitive.aspx. Accessed April 9, 2010.
3. Diagnostic and Statistical Manual for Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
4. Diagnostic and Statistical Manual for Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994.
5. Diagnostic and Statistical Manual for Mental Disorders. 3rd ed. Washington, DC: American Psychiatric Association; 1980.
6. Graeber MB, Kösel S, Egensperger R, Banati RB, Müller U, Bise K, Hoff P, Möller HJ, Fujisawa K, Mehraein P. Rediscovery of the case described by Alois Alzheimer in 1911: historical, histological and molecular genetic analysis. Neurogenetics. 1997;1(1):73-80.
7. International Statistical Classification of Diseases and Related Health Problems. 6th rev. Geneva, Switzerland: World Health Organization; 1948.
8. Diagnostic and Statistical Manual for Mental Disorders. Washington, DC: American Psychiatric Association; 1952.
9. Kramer M. Introduction: the historical background of ICD-8. In: Diagnostic and Statistical Manual for Mental Disorders. 2nd ed. Washington, DC: American Psychiatric Association; 1968:xi-xv.
10. Diagnostic and Statistical Manual for Mental Disorders. 2nd ed. Washington, DC: American Psychiatric Association; 1968.
11. International Statistical Classification of Diseases and Related Health Problems. 8th rev. Geneva, Switzerland: World Health Organization; 1968.
12. Medicaid Requirements for OMH-Licensed Outpatient Programs. NYS Office of Mental Health. January 2004. Available at: www.omh.state.ny.us/omhweb/012104letter/medicaid.htm. Accessed April 16, 2010.
13. Okura T, Plassman BL, Steffens DC, Llewellyn DJ, Potter GG, Langa KM. Prevalence of neurospychiatic symptoms and their association with functional limitation in older adults in the United States: The Aging, Demographics, and Memory Study. J Am Geriatr Soc. 2010;58(2):330-337.
14. Lyketsos CG, Sheppard JM, Steinberg M, et al. Neuropsychiatric disturbance in Alzheimer’s disease clusters into three groups. Int J Geriatr Psychiatry. 2001;16(11):1043-1053.
15. Devanand DP, Jacobs DM, Tang MX, et al. The course of psychopathological features in mild to moderate Alzheimer’s disease. Arch Gen Psychiatry. 1997;54(3):257-263.
16. Holtzer R, Verghese J, Wang C, Hall CB, Lipton RB. Within-person across-neuropsychological test variability and incident dementia. JAMA. 2008;300(7):823-830.
17. Griffith HR, Stewart CC, Stoekel LE, et al. Magnetic resonance imaging volume of the angular gyri predicts financial skill deficits in people with amnestic mild cognitive impairment. J Am Geriatr Soc. 2010;58(2):265-274.
18. Kennedy GJ. From symptom palliation to disease modification: implications for dementia care. Primary Psychiatry. 2007;14(11):30-34.
19. Meiklejohn ST, Brehmer B, Chase I, Greenberg D. To the Editor. A separate label for Asperger’s. New York Times. February 15, 2010:A29.

 

Dr. Sussman is editor of Primary Psychiatry as well as Associate Dean for Post-Graduate Programs and professor 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.

Email questions or comments to ns@mblcommunications.com


 

Selecting the best strategy to optimize antidepressant response is a major ongoing clinical challenge. The need for more effective approaches for producing remission has been made clear by recent evidence that confirms treatment with any single antidepressant drug produces remission in only ~33% of patients, and that when antidepressants do work, they are of most benefit to those with more severe depressive symptoms. Patients with moderate levels of depression who seek care because they are either distressed or impaired by their symptoms may, paradoxically, be more difficult to bring into remission than those with a more pronounced disorder. An abundance of studies have shown that numerous augmentation or switching strategies may be effective for some patients, but no body of evidence demonstrates consistent superiority of any. In summarizing lessons learned from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, the most ambitious attempt to date to address the question of antidepressant enhancement options, Rush wrote that “the gap between what we do in practice and what we know is very large.”1 In the near future, another study should be published that looks at whether it is better to start treatment with a combination of antidepressants rather than monotherapy. In anticipation of that article, I want to review the STAR*D trial and its major finding and describe the Combining Medication to Enhance Depression Outcomes (CO-MED), which looks at whether it is better to start treatment with two drugs instead of one.

 

STAR*D

STAR*D focused on non-psychotic major depressive disorder (MDD) in adult outpatients. The primary purpose of this research study was to determine which treatments work best if the first treatment with medication does not produce an acceptable response. All participants at first received the selective serotonin reuptake inhibitor (SSRI) citalopram (open label). If symptoms remained after 8–12 weeks of treatment, up to four other levels of treatment were offered, including cognitive therapy and other medications (Table 1). There was no placebo treatment option.

The study involved a highly representative clinical sample of depressed outpatients. In that regard, the STAR*D population was different than the highly selective cohort usually enrolled in industry-sponsored clinical trials.

At each level change, participants were asked to indicate the unacceptability of the potential treatment strategies (eg, to augment or to switch medications). Participants were then be eligible for random assignment the next treatment options.

Level 2

Participants who either did not have an adequate response to or could not tolerate citalopram are eligible for Level 2. The Level 2 treatment strategies were:

 

i) Medication and Psychotherapy Switch: switch to sertraline, venlafaxine extended release (XR), bupropion sustained release (SR), or cognitive therapy (CT).
ii) Medication and Psychotherapy Augmentation: add to citalopram either a) buspirone, b) bupropion SR, or c) CT.
iii) Medication Only Switch or Medication Only Augmentation: options were available for participants for whom CT is
unacceptable.
iv) Psychotherapy Only Switch or Psychotherapy Only Augmentation: options were available for participants for whom additional medication is unacceptable at this point in the study (participants must be willing to continue citalopram)

 

Level 2A

Participants without a satisfactory response to their Level 2 treatment were eligible for random assignment to additional treatment at Level 2A. Level 2A was included so that all participants entering Level 3 had an opportunity to respond to at least two medications. Level 2A consisted of medication switch to one of two antidepressants (venlafaxine XR or bupropion SR).

 

Level 3

Participants without satisfactory response to Level 2 and, if appropriate Level 2A, were eligible for random assignment to one of the following treatments:
i) Medication Switch to: a) mirtazapine or b) nortriptyline, a tricyclic antidepressant.
ii) Medication Augmentation: add (to current Level 2 or Level 2A medication) either: a) lithium or b) thyroid hormone (T3).

 

Level 4

Participants without an adequate response to Level 3 were eligible for random assignment to Level 4 treatment. Level 4 includes two medication switch options: to tranylcypromine (a monoamine oxidase inhibitor), or to mirtazapine plus venlafaxine XR.

 

CO-MED

The study, which cost $35 million, failed to find any significant differences between drugs at each step in terms of the primary outcome measure, which was remission of depression. While there have been other significant findings from the study, the data did inform practitioners about “next step” management of patients with who fail on initial therapy.

CO-MED, like the STAR*D trial, was National Institute of Mental Health sponsored.2 Completed in late 2009, the results of this research have not been published. In contrast to STAR*D, this study compared whether a combination of antidepressants is better than one antidepressant alone when administered as initial treatment for people with chronic or recurrent MDD. CO-MED was designed to test whether two different medications when given in combination as the first treatment step, compared to one medication, enhances remission rates, increases speed of remission, is well tolerated, and provides better sustained benefits in the longer term. There were two arms to the study.

In Arm A, one of the following were given along with placebo: bupropion, escitalopram, mirtazapine, or venlafaxine.

In Arm B, two of the following drugs were given in combination: bupropion, escitalopram, mirtazapine or venlafaxine (Table 2).

Hopefully, the results of CO-MED will prove less nihilistic than those of the STAR*D trial with respect to answering the major question: Which treatment works best? One of the more disappointing aspects of both studies is that neither one looked at the use of a second-generation antipsychotic as an add-on treatment. Given that we now have increasing use of these drugs to augment antidepressants, it would be reassuring to have comparative data on both the safety and effectiveness of this approach.

 

Conclusion

Perhaps the answers we are looking for in terms of predicting treatment response may not come from large comparative clinical trials, but from molecular psychiatry research.

I want to thank David A. Mrazek, MD, FRCPsych, for serving as guest editor for this issue. Pharmacogenomic testing, he observes, may soon become standard practice based on the patient-specific evidence base that already exists. The four articles in this issue that address progress in individualized molecular psychiatry hint at the possibility, he notes, that we will be able to abandon our traditional trial and error approach to medication selection and begin providing our patients safer and more effective individualized psychopharmacologic treatments.

I also direct your attention to an article by Racha Nazir, MD, and colleagues regarding advice on starting the outpatient clinic. It touches on practical issues as office design, charting, knowledge of pharmacotherapy and psychotherapy, and individualization of patient care.

This issue marks the introduction of a new bi-monthly column titled “Clinical Updates in Child & Adolescent Psychiatry” by Margaret D. Weiss, PhD. Dr. Weiss is the head of the Provincial ADHD Program and clinical professor at the University of British Columbia Children’s & Women’s Health Centre in Vancouver, Canada. The column will highlight the clinical approaches, science, and new developments in child psychiatry. I look forward to her contributions and hope our reader-practitioners find the information useful.  PP

 

References

1. Rush AJ. STAR*D: what have we learned? Am J Psychiatry. 2007;164(2):201-204
2. Combining Medications to Enhance Depression Outcomes (CO-MED). Available at: http://clinicaltrials.gov/ct2/show/NCT00590863. Accessed April 19, 2010.

 

Researchers Analyze Prescription Rates for Psychiatric Medications

Tami K. Mark, PhD, and colleagues analyzed data from the 2005 National Disease and Therapeutic Index (NDTI) in order to examine which disease states psychiatric medications were being prescribed for. The NDTI is a continuing survey of over 4,000 office-based United States-based physicians. These physicians provide quarterly reports detailing their contact with patients and recording patient demographics, diagnosis, and therapies.
 

Via an e-mail interview, Dr. Mark stated their reasoning for conducting this research: “As part of an ongoing SAMHSA study to document how much is spent on mental health care in the US, we regularly conduct focused studies to better understand how specific types of mental health services are provided. In the area of psychotopic medications, we were frequently being asked whether most spending was for psychiatric illnesses, or whether it was often for medical illnesses, some of which may be off-label. We thus set out to better document the reasons why physicians were prescribing psychiatric medications.”
 

Mark and colleagues found that ~93% of antidepressants were prescribed for psychiatric conditions. Mood disorders accounted for 65.3% of mentions and anxiety disorders accounted for 16.4%. They also found that ~67% of anti-anxiety medications were prescribed for psychiatric conditions, with anxiety disorders accounted for ~40% of mentions and mood disorders accounted for ~19%.
 

They also found that ~99% of antipsychotics were prescribed for psychiatric conditions. Mood disorders, such as depression and bipolar disorder, accounted for 39% of mentions and schizophrenia or other psychiatric disorders accounted for 34.5% of mentions. Delirium, dementia, amnestic or other cognitive disorders accounted for 7.4% of drug mentions. Attention-deficit/hyperactivity disorder (ADHD) accounted for 5.7% of mentions and anxiety disorders accounted for 5.5%. Disorders diagnosed in infancy/childhood/adolescence, such as autism, accounted for 2.3% of mentions. Whether or not the prescription was on- or off-label was not part of the analysis.
 

“We were somewhat surprised at the small amount of non-psychiatric use of antidepressants (only ~7%) because some prior smaller studies found higher uses for medical purposes such as headache and chronic pain. The fact that ~33% of anti-anxiety medications were not prescribed for psychiatric diagnoses was also interesting. Approximately 6% of prescriptions were indicated as prescribed for a ‘medication examination/evaluation,’ thus presumably to relieve anxiety associated with the interventions.
 

“There has been considerable discussion in the scientific literature about the widening use of antipsychotics for a variety of psychiatric conditions and this study systematically documents this phenomenon. We found that the most common use for antipsychotics was not schizophrenia, but mood disorders, and that use for ADHD and dementia were common, despite being off-label,” Dr. Mark wrote.
 

The researchers hope that this analysis will be able to serve as a guide for future research, policy, and education about psychiatric medications, as well as their benefits, risks, and uses.
 

Funding for this research was provided by the Substance Abuse and Mental Health Services Administration to Thomson Reuters. (CNS Drugs. 2010;24(4):319-326). –CN
 

Rapid Cycling More Likely in Patients With Bipolar Disorder and Comorbid Substance Abuse

A recent study provided new evidence regarding specific characteristics that differentiate patients with bipolar disorder and comorbid substance use disorders (SUDs) from those who do not have comorbid SUDs.
 

Data were derived from the largest study on the treatment of bipolar disorder, the Systemic Treatment Enhancement Program, in which 2,154 patients with a diagnosis of bipolar I or II disorder who experienced a new-onset depressive episode were analyzed. Approximately 44% of patients had current or prior alcohol use, and 30% had a past or current drug use disorder. It was found that the likelihood of switching did not differ significantly between patients with prior SUDs and those with current SUDs. Therefore, the risk for direct switch in these patients was not induced or worsened by ongoing substance use.
 

An unexpected finding was that patients’ recovery time from a major depressive episode was not affected by whether patients had comorbid SUDs. Neither current nor prior substance use was thought to delay recovery from a depressive episode; therefore, patients did not suffer longer depressive episodes than patients without SUDs.
 

Lead researcher, Michael Ostacher, MD, MPH, of Massachusetts General Hospital and Harvard Medical School stated: “The results from this study suggest that treating patients with bipolar disorder for depression, even if they have a drug or alcohol problem, is no less successful than if they have no substance problem. This means that the standard guidelines for the treatment of bipolar disorder can be used for patients regardless of drug or alcohol problems.”
 

Defined as ≥4 mood episodes in the previous year, rapid cycling was more common in patients with prior or current alcohol use disorders, but had no significant correlation with prior or current drug use disorders. Based on these findings, the authors propose that patients with concomitant bipolar disorder and SUDs may have a set of inherent characteristics different from those of patients with bipolar disorder and no substance abuse.
 

“Patients with bipolar disorder and concomitant SUDs tend to be more ill. They are more likely to have attempted suicide, have more prior episodes, do not appear to function as well, are less likely to adhere to treatment, and are more likely to be violent,” explained Dr. Ostacher.
 

Regarding treatment of patients with SUDs, Dr. Ostacher added: “First, patients should be counseled to moderate or stop their use. Motivational interviewing techniques should be used to engage patients in a process of behavioral change, and referral for specialized treatment should be made. Treatments that are approved for drug or alcohol dependence should be used, especially considering the absence of data showing their ineffectiveness in comorbid bipolar disorder.”
 

Funding for this study was provided by the National Institute of Mental Health. (Am J Psychiatry. March 15, 2010 [Epub ahead of print]) –JV
 

Interpersonal Psychotherapy for Adolescent Girls at Risk for Adult Obesity

A recent study suggests that interpersonal psychotherapy (IPT) may help prevent weight gain and binge eating in adolescent girls at risk for adult obesity.
 

Marian Tanofsky-Kraff, PhD, at the Uniformed Services University of the Health Sciences in Maryland, and colleagues, evaluated the 1-year outcomes of IPT compared to general health education. Thirty-eight adolescent girls (12–17 years of age) at risk for adult obesity (body mass index in the 75th-97th percentile) were randomized to IPT or a health education group. Twenty of the 38 girls had out of control eating patterns at baseline.
 

According to previous studies, IPT can effectively reduce binge-eating behavior in obese adults and help stabilize the weight gain associated with binge eating. One goal of IPT is to demonstrate to patients the influences of social interaction, and especially negative social interaction. In this study, patients in the IPT group were encouraged to appreciate how their own spoken communication and, for example, body language, affects interaction with others. By moving toward more frequent positive social interactions, the goal was to lessen, or eliminate, any number of negative stimuli that might cause the patients to respond by eating.
 

Thirty-five patients returned to 1-year follow-up. Patients with out of control eating, who were in the IPT group, had greater reductions in those behaviors than those in the health education group (P=.036). Regardless of out of control eating status, IPT patients also showed greater weight stabilization at 1-year follow-up.
 

Funding for this study was provided by the National Institutes of Health and the Uniformed Services University of the Health Sciences. (Int J Eat Disord. Oct 30, 2009 [epub ahead of print]). –LS
 

Psychiatric dispatches is written by Christopher Naccari, Lonnie Stoltzfoos, and Jennifer Verlangieri.

 

Dr. Nazir is post-doctoral fellow and Dr. Sedky is associate professor of psychiatry at the Hershey Medical Center in Pennsylvania. Dr. Paladugu is an observer and Dr. Lippmann is professor of psychiatry at the University of Louisville School of Medicine in Kentucky.

Disclosure: The authors report no affiliation with or financial interest in any organization that may pose a conflict of interest.

Please direct all correspondence to: Karim Sedky, MD, Department of Psychiatry, Hershey Medical Center, 500 University Drive, Mail Code H073, Hershey, PA 17033; Tel: 717-782-2180; Fax: 717-782-2190; E-mail: sedky66@hotmail.com.


Abstract

Residents benefit by being prepared for their outpatient rotation. Coming to the clinic with an understanding of the procedures, challenges, and how to meet educational objectives should promote confidence and a better educational experience. Learning how to adjust to this setting, arrange their office, get supervision, and provide good clinical service are important steps in the resident’s training. Assuring access to faculty guidance at pharmacotherapy and psychotherapy facilitates expertise and safety for the patient and trainee. Understanding administrative and practical aspects of psychiatric care in this setting fosters a good clinical approach and education in a supervised, productive manner.


Focus Points

• Office design is important and includes a focus on safety.
• Charting is important for clinical, insurance, and medico-legal reasons.
• Missed appointments are frequently encountered in outpatient settings.
• It is important to learn pharmacotherapy and psychotherapy.
• Patient care is individualized to specific patient needs.

 

Introduction

The outpatient clinic is one of the principal sites for training psychiatry residents. The Accreditation Council of Graduate Medical Education for psychiatry requires at least 1 year of outpatient experience for trainees.1

Most residencies start psychiatric training on inpatient services in the first postgraduate year. There, the resident acquires an understanding about psychopathology. Risk assessment, diagnostic evaluation, and formulating a differential diagnosis are mastered during this phase of training. It also offers an opportunity for prescribing medication under supervision and learning about aftercare options.

Residency may vary with respect to when residents begin to see outpatients. Before starting, it is important to learn about the clinic policies. Ambulatory patients exhibit a wide range of exposures. Certain conditions, such as obsessive-compulsive disorder (OCD), are seen in this setting more often than in a hospital service. Having residents continue clinic work as long as possible improves patient and physician satisfaction through a longer-term relationship. Therapeutic alliances are enhanced and it affords the resident an opportunity to observe the course of mental illness over time.2

Residents typically have at least one outpatient supervisor. Especially during the adjustment phase, supervisors provide orientation to the clinic. They offer professional advice, clinical guidance, and other assistance throughout the rotation. Discussion may include guidance on study of appropriate educational materials; prescribing pharmacotherapies; and help in handling referrals, complaints, and so forth. Residents also meet with their supervisors to review psychotherapeutic techniques and alternatives. Self-educational reading and attending lectures or conferences is usually required.

 

What About Your Office?

For safety reasons, the clinician’s chair should ideally be nearer to the door than is the patient’s chair. Some clinics place an emergency alarm button at the desk or some other alert system to call for help, if protection is needed. Extra seating is made available for family. A box of tissues should always be available.

The room should be well illuminated. There is controversy about whether to display pictures of one’s family. From a psychoanalytic point, this may not be advisable. Pictures on the wall should have a calmative theme. Plants beautify the room and promote a pleasant atmosphere, as long as they are healthy.

 

Schedules

Clinics differ in respect to scheduling of team meetings where referrals, clerical issues, and other problems are discussed. These meetings often review clinically difficult cases and administrative issues.

In cases of conjoint treatment with a psychotherapist, frequent contact between both clinicians is expected for information sharing. Billing is usually new to residents, but it is essential to learn the coding system for intakes, medication checks, psychotherapy sessions, and other patient contacts.

 

How To Chart

Legible documentation is important. Typing is clearer than handwriting, and printed clinical recording sheets for patient data also can simplify charting. Maintain appropriate eye contact with the patient when recording information. Note the date and time of each session, including the start and ending time and the duration of the visit. Document general content of the session, complaints, concerns, and therapy utilized. Include details about patient progress, efficacy of pharmacotherapy, and any side effects. Clinical data should support the type of session noted on the billing forms.

The chart should reflect a discussion of safety concerns and decisions about management. Safety includes suicidal or homicidal thoughts, inability to take care of oneself, abuse, or noncompliance with medical treatment. In these situations, consultation with the supervisor is advised and documented before ending the appointment. Child Protective Services must be notified whenever there is possible abuse to a minor. Adult Protective Services are informed if an adult is unable to care for him- or herself or is being abused.

 

About Tarasoff

It is important to be familiar with the Tarasoff ruling. In cases of expressed dangerous threats to others, clinicians have the duty to protect the potential victim by a direct warning to that individual and to the police; this can often be done without compromising the therapeutic relationship.3 When a patient refuses to reveal information about the possible victim, inform the local police department. These facts must always be documented in the chart.

 

First Appointment

Clinics differ with respect to who schedules the initial appointments, provides the clinic’s address and phone number, and answer questions, such as how to access parking. The first 1-hour session is dedicated to evaluating the patient with a history and mental status examination, followed by discussion of treatment plans. Laboratory tests may be ordered as needed. Therapeutic decisions are postponed in complex cases until the required information is obtained and reviewed with the supervisor. Collateral information from family members or a previous treatment team might be beneficial. Some patients may require more intensive treatment with referral to specialty clinics, as for persons with dangerous self-mutilation or substance abuse.

Written consents are obtained from patients before information is revealed to a third party, even to family or an insurance company. Special consents are obtained for video or audio taping a session.

Treatment discussions include pharmaceutical options as well as psychotherapy selections. Always tell patients whom to call in case of emergency, during working hours or when the clinic is closed. If there is overt concern for patient safety, involve family for monitoring. Although assessments are more accurate when the supervisor and the trainee conduct concluding parts of the initial interview together, this is usually not done for practical reasons.4

 

Follow Up

A follow-up visit is mutually agreed upon by the patient and resident. Some clinics depend on secretaries to schedule appointments, but the doctors must inform staff about their available times and planned visit dates. The clinic phone number, emergency contacts, and physician’s name should be provided to every patient. The next follow-up date and time should be given to the patient in written form.

 

Missed Visits

Residents should be aware of clinic policy towards individuals who frequently miss appointments. Every outpatient facility has its own way to deal with missed visits. Failure to appear for an appointment is most common among people seen by a resident, in younger patients, and for those individuals with a record of missed visits or living far from the facility.5

 

Pharmacotherapy

Prescribing medications is a frequent part of treatment. There are algorithms available for treatment of different syndromes6 and the American Psychiatric Association offers downloadable guidelines.7 Drug interactions between psychopharmaceuticals and other co-administered medical treatments must always be considered. Avoid polypharmacy when possible.8,9 The physiologic impact of medications must always be considered; for example, avoid lithium during pregnancy, lactation, renal dysfunction, or hypothyroidism.

Residents should know which medications cause weight gain.10 Patients taking antipsychotics should be monitored for the metabolic syndrome according to the current guidelines. Side effects should be discussed and charted.

Always consider the prospect of pregnancy to avoid teratogenicity from pharmaceutical exposure in female patients of child-bearing age. Pharmacotherapy is avoided if possible during pregnancy or lactation. The risk versus benefit of using medications during pregnancy mandates explicit indications and thorough discussion; consultation with a supervisor and an obstetrician is essential. Be aware that efficacy of oral contraceptives in preventing pregnancy is reduced when co-prescribed with hepatic enzyme-inducing drugs, like carbamazepine.

For patients taking benzodiazepines or other controlled substances, continued benefit should be consistently and specifically charted; taper off such medications when possible. Controlled substances, as in treatment for insomnia, should ideally be prescribed only for short periods. For patients with alcohol and/or drug abuse, sobriety is consistently stressed. Alcoholics Anonymous or Narcotics Anonymous are encouraged, buprenorphine administration is considered, and/or other chemical dependency intervention plans are implemented. Some programs offer special training to residents at handling drug abuse cases.11 Any controlled substances in the clinic, like buprenorphine, must be kept in a locked location. Needles and injectable medicines should be stored in secure places, with refrigeration as needed.

Always consider the cost of medication and insurance coverage in planning treatment. Pharmaceutical sales representative visits often inappropriately influence resident prescribing habits. Thus, this practice is now discouraged.12

 

Individual Versus Conjoint Treatment

Residents can do both medication management and psychotherapy. This allows more time to understand the patient and improves the therapeutic alliance. However, having two people share a case can also be clinically beneficial, and is often the reality.

 

Psychotherapy

After the assessment, the clinician and supervisor determine the type of psychotherapy indicated. Consider patient education, motivation, energy, and functional capacity. Availability, times for sessions, and financial aspects should be reviewed.

Supportive therapy is indicated, especially for those recently discharged from the hospital, after an acute relapse, or those with compromised function. Cognitive-behavioral therapy is a frequently chosen treatment that focuses on cognitive distortions and automatic thoughts.13 In cases of phobias, posttraumatic stress disorder, or OCD, exposure with response prevention is a frequent option. If there is a concern about self-harm, dialectical-behavioral therapy might be selected.14 This includes teaching interpersonal effectiveness, stress tolerance, acceptance skills, and emotional regulation.15 Mentalization therapy is an alternative for treating patients with borderline personality disorder by helping them develop stability within a secure attachment relationship.16 Learning psychodynamic psychotherapy is a core training requirement and utilized in selected cases.17 For those who have chemical dependence issues, one can encourage abstinence by motivational enhancement therapy through a guided review of ambivalences.

Other therapeutic options include group approaches, family or marital counseling, hypnotherapy, or other traditional or even less conventional therapies. It can be advantageous when different supervisors suggest alternative approaches, even in the same patient.18 Electroconvulsive therapy may be indicated as a somatic treatment in certain cases. Transcranial magnetic stimulation and vagal nerve stimulation are newer considerations.

 

Crisis Assesment And Community Treatment Team

During a psychiatric emergency, a crisis team or the regular clinical staff must provide an immediate assessment and/or referral to inpatient hospitalization. For chronically ill, low-functioning individuals, a referral to a community treatment program is appropriate since these agencies have an intense assistance program provided by multidisciplinary professionals.

 

Forms And Letters

Some patients may have forms for physician signature. Others may ask for social security or insurance papers to be filled out. Excuses for job or school absences are often requested. The same applies to notices about returning to work and clarifying occupational restrictions. Place copies of all forms and similar papers in the chart to document the transaction. An appreciation of disability regulations can be an aid in assisting patients.19

 

Referral

It is important that residents know how to access other services. These may include physician referrals such as securing a psychologist, social worker, nurse practitioner, Meals-on-Wheels, transportation services, or vocational rehabilitation. Knowledge of community resources is expected.20

 

Laboratory Tests

At the initial evaluation, laboratory screening is considered. This may include a complete blood count, lipid profile, comprehensive serum chemistry profile, urinalysis, or thyroid hormone assays. A serum pregnancy test is conducted in women of childbearing potential. Various tests may be repeated over time, eg, serum glucose or lipid monitoring when metabolic syndrome is a concern. Neuroimaging is requested when brain disease is in the differential. Syphilis or other infectious disease testing is indicated in demented or other selected people. Clozapine prescribing mandates hematologic follow up regularly with special attention to the neutrophil count. Lithium requires attention to serum levels, renal effects, and antithyroid properties as well as pre-treatment testing. Blood counts, liver or renal function tests, hepatic enzyme assays, or electrolytes are monitored regularly in patients taking medications with adverse potential in these areas. The procedures for ordering tests vary from clinic to clinic.
 

Samples/Returned Medications

It is important to be familiar with the policy for handling medication samples. Many clinics do not allow sampling of pharmaceuticals, but some facilities still do, under tight regulation.
 

Special Populations

Training residents about cultural differences is important.21-23 For example, African-American populations reportedly are often overdiagnosed with schizophrenia.24 Hispanic populations may have a higher incidence of anxiety disorders.25 Interpreter services are required in cases with a language barrier. Adjustment disorders and non-acceptance by family are frequent complaints by homosexuals.26 Training guidelines exist for women’s issues.27 When treating children or adolescents, family therapy is an integral part of the plan.28-30
 

Transfering Or Terminating

Sometimes a resident might need to transfer a patient. These situations could include transference or counter-transference issues, concern about physician safety, lack of progress, and always at times when the resident will no longer be available. It is important to explain the reasons for transfers. In long-term therapeutic relationships, discussion focuses on analysis of feelings and future plans. Self-esteem and abandonment issues should be addressed. At the end of the outpatient rotation, detailed discussions should ensue and consider even introducing the patient to the new therapist to avoid feelings of abandonment. A review of the newly arranged follow up is mandatory with names, dates, times, and phone numbers listed on a new appointment card.

 

Conclusion

The outpatient clinic is an important part of the psychiatric education. Preparing residents before they start the ambulatory rotation reduces anxiety and improves the educational experience. Understanding the practice policies of the clinic helps the resident to be comfortable and productive. Following patients for long duration offers trainees a long-term view of patient pathology, problems, and coping skills. Performing medication management and psychotherapy with expertise are important objectives. Education also focuses on forming therapeutic relationships, monitoring disease progression and/or effectiveness of treatment, and competently handling mental health emergencies. Learning about ambulatory care comes from practical experience in the clinic.  PP
 

References

1.    ACGME-Residency Review Committee Guidelines. Available at: www.acgme.org/acWebsite/downloads/RRC_progReq/400pr1104.pdf. Accessed on March 8, 2010.
2.    Steinbook R. Continuity clinics in psychiatric residency training. Acad Psychiatry. 2007;31(1):15-18.
3.    Binder RL, McNiel DE. Application of the Tarasoff ruling and its effect on the victim and the therapeutic relationship. Psychiatr Serv. 1996;47(11):1212-1215.
4.    Stein SP, Karasu TB, Charles ES, et al. Supervision of the initial interview. A study of two methods. Arch Gen Psychiatry. 1975;32(2):265-268.
5.    Campbell B, Staley D, Matas M. Who misses appointments? An empirical analysis. Can J Psychiatry. 1991;36(3):223-225.
6.    Texas Manuals and Algorithms. Available at: www.dshs.state.tx.us/mhprograms/disclaimer.shtm. Accessed on March 8, 2010.
7.    American Psychiatric Association Practice Guidelines. Available at: http://psych.org/psych_pract/treatg/pg/prac_guide.cfm. Accessed on March 8, 2010.
8.    Caine E, Lyness J. Delirium, dementia, and amnestic and other cognitive disorders. In: Sadock BJ, Sadock VA. Kaplan and Sadock’s Synopsis of Psychiatry. 10th ed. Pennsylvania, PA: Lippincott, Williams and Wilkins; 2007:323.
9.    Glezer A, Byatt N, Cook R Jr, Rothschild AJ. Polypharmacy prevalence in the treatment of unipolar depression in an outpatient clinic. J Affect Disord. 2009;117(1-2):18-23.
10.    Vanina Y, Podolskaya A, Sedky K, et al. Body weight changes associated with psychopharmacology. Psychiatr Serv. 2002;53(7):842-847.
11.    Renner JA Jr. How to train residents to identify and treat dual diagnosis patients. Biol Psychiatry. 2004;56(10):810-816.
12.    Schwartz TL, Kules DJ, Wade M, et al. Newly admitted psychiatric patients’ prescriptions and pharmaceutical sales visits. Ann Clin Psychiatry. 2001;13(3):159-162.
13.    Beck J. Cognitive Therapy: Basics and Beyond. New York, NY: Guilford Press; 1995.
14.    Linehan M. Cognitive-Behavioral Treatment of Borderline Personality Disorder. New York, NY: Guilford Press; 1993.
15.    Linehan MM, Armstrong HE, Suarez A, Allmon D, Heard HL. Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry. 1991;48(12):1060-1064.
16.    Bateman A, Fonagy P. Psychotherapy for Borderline Personality Disorder: Mentalization-based Treatment. Norfolk, UK: Oxford Medical Publication; 2004.
17.    Mullen L, Rieder R, Glick R, Luber B, Rosen PJ. Testing psychodynamic psychotherapy skills among psychiatric residents: the Psychodynamic Psychotherapy Competency test. Am J Psychiatry. 2004;161(9):1658-1664.
18.    Nestler EJ. The case of double supervision: a resident’s perspective on common problems in psychotherapy supervision. Acad Psychiatry. 1990;14:129-136.
19.    Mischoulon D. An approach to the patient seeking psychiatric disability benefits. Acad Psychiatry. 1999;23(3):128-136.
20.    Kramer T, Kennedy R. Educational computing. Useful websites for psychiatrist. Acad Psychiatry. 1998;22:141-143.
21.    Harris H, Felder D, Clark M. A psychiatric residency curriculum on the care of African American patients. Acad Psychiatry. 2004;28(3):226-239.
22.    Garza-Trevino ES, Ruiz P, Venegas-Samuels K. A psychiatric curriculum directed to the care of the Hispanic patient. Acad Psychiatry. 1997;21:1-10.
23.    Stein TS. A curriculum for learning in psychiatric residencies about homosexuality, gay men, and lesbians. Acad Psychiatry. 1994;18:59-70.
24.    Hausman K. Cultural factors affect success of African Americans’ MN care. Psych News. 2001;36(10):17.
25.    Hirai M, Stanley MA, Novy DM. Generalized anxiety disorder in Hispanics. Symptom characteristics and prediction of severity. J Psychopath Behav Assessment. 2006;28(1):49-56.
26.    Anhalt K, Morris T. Developmental and adjustment issues of gay, lesbian, and bisexual adolescents: a review of the empirical literature. Clin Child Family Psych Rev. 1998;1(4):215-230.
27.    Spielvogel AM, Dickstein LJ, Robinson GE. A psychiatric residency curriculum about gender and women’s issues. Acad Psychiatry. 1995;19:187-201.
28.    Celan M, Croft S, Morrissey-Kane E. Family Evaluation Clinic. Training psychiatrists to think systemically. Acad Psychiatry. 2002;26:17-25.
29.    Berman EM, Heru AM, Grunebaum H, et al. Family skills for general psychiatry residents: meeting ACGME core competency requirements. Acad Psychiatry. 2006;30:69-78.
30.    Berman EM, Heru AM, Grunebaum H, et al. Family-oriented patient care through the residency training cycle. Acad Psychiatry. 2008;32:111-118.

 

Dr. Sharma is professor and head of psychiatry at Indira Gandhi Medical College & Hospital in Shimla, Himachal Pradesh, India. Mr. Thakur is surgeon at Civil Hospital Rampur in Shimla.

Disclosure: The authors report no affiliation with or financial interest in any organization that may pose a conflict of interest.

Please direct all correspondence to: Ravi C. Sharma, MD, Professor & Head, Department of Psychiatry, Indira Gandhi Medical College & Hospital, Shimla (171001), Himachal Pradesh, India.
Tel: 91-177-2844644; Fax: 91-177-2658339; E-mail: ravi82000@yahoo.com.


 

Abstract

Acute urinary retention as a conversion symptom has received little attention in the literature and has been mostly considered as a diagnosis per exclusion. This is a case report of 20-year-old female who presented with acute retention of urine as a conversion symptom with strong psychological antecedents; she recovered completely by removing secondary gain, giving suggestions, and undergoing family counselling.

 

Introduction

There is a scarcity of information in the literature about the cause and management of acute urinary retention in females in comparison to males.1 The causes of acute urinary retention can be divided into four etiologic groups: obstructive, neurologic, pharmacologic, and psychogenic.2 Females presenting with urinary retention in the absence of any identifiable neuro-anatomic cause for their symptom pose a diagnostic and management challenge and may be dismissed as psychogenic cases.3 The present case report highlights the importance of identifying and resolving psychological factors leading to acute urinary retention in a young female.
 

Case report

A 20-year-old unmarried female, student of class 12, presented in the Surgical Out Patient Department (OPD) of our hospital with the complaint of acute retention of urine. She gave a history of intermittent catheterization at the local primary health center thrice over the past 5 days after which she was referred to our hospital. There was no history of similar complaints in the past. Examination of the patient was unremarkable except for the palpable bladder. The patient was catheterized and investigated for retention of urine and urinary tract infection. Her urine routine as well as microscopic and culture examination were normal. Plain X-ray of the abdomen region, ultrasound of the abdomen, and pelvic organs were also normal. The patient was put on empirical treatment in the form of tablet ofloxacin 200 mg BID and hyoscine butyl bromide 10 mg TID, and was given a catheter-free trial which proved futile because she again developed retention. Psychiatric opinion was sought as the patient was not responding to the treatment, and urodynamic evaluation was planned.
 

Psychiatric evaluation revealed that the female who came from a rural nuclear family had been facing severe psychosocial stress due to her father who frequently used to quarrel with his wife and scold the patient quite often after consuming alcohol. Just a day prior to the onset of her symptoms, the patient’s father had created a ruckus in the house and had physically assaulted the patient. The patient was an average student and was described to be sincere, sensitive, and passive by nature. The initial mental state examination was unremarkable; however, on subsequent exploration the patient was found to be preoccupied with her ongoing family stress but was oblivious to her physical symptom (la belle indifference). In the absence of any evident physical cause for urinary retention and strong temporal association of the symptom with the family stress, the patient was diagnosed as a case of “Conversion Reaction” as per the International Classification of Diseases, Tenth Revision,4 criteria.
 

The secondary gain the patient was receiving from her relatives and medical professionals was minimized and she was given strong suggestions. She was also prescribed fluoxetine 20 mg/day along with alprazolam 0.25 mg at bed time. Her parents were counselled in detail and role of stress in the genesis of this symptom was explained. The father of the patient was enrolled for further evaluation and management of alcohol dependence in the psychiatry OPD. The patient’s catheter was removed the third day; she started passing urine normally and was discharged on the above medications with advice to follow up after 7 days in the psychiatry OPD. On follow-up visit the patient reported that she did not take any medications at home and was completely asymptomatic. The patient had been maintaining well even after 3 months of discharge when she last came for follow-up.

 

Conclusion

Urinary dysfunction due to psychogenic causes like conversion reaction and anxiety has been reported both in males and females.5 Psychogenic urinary retention has been described more frequently in young adult females with history of childhood enuresis and disturbed social backgrounds. Such patients have been frequently diagnosed as “hysteric,” with their symptom representing a displacement of unacceptable sexual wishes and impulse.6
 

In one study,7 psychogenic factors have been cited as the second important cause of retention of urine in females. The role of psychological disturbances in the genesis of acute and chronic urinary retention in females has also been reported by other authors.8-10 In the patient presented, there was no evidence of any physical or organic cause to explain her retention of urine, but there was a definite evidence of a family stressor preceding the development of this retention. Furthermore, the symptom resolved completely after appropriate suggestions, cutting down secondary gain, and family counseling. Therefore, the retention of urine in the present case qualifies to be labelled as conversion symptom.
 

The present case highlights the need for looking in to and resolving precipitating and or perpetuating psychological stressors also as a cause of acute urinary retention, especially in young females, before subjecting them to unnecessary urodynamic investigations and repeated catheterizations.  PP

 

References

1.    Barone JG, Berger Y. Acute urinary retention in females. Int Urogynecol J. 1993;4(3):152-156.
2.    Vander Linden EF, Venema PL. Acute urinary retention in women. Ned Tijdschr Geneeskd. 1998;142(28):1603-1606.
3.    Kavia RB, Datta SN, Dasgupta R, et al. Urinary retention in women: its causes and management. BJU Int. 2006;97(2):281-287.
4.    International Classification of Diseases. 10th rev. Geneva, Switzerland: World Health Organization; 1992.
5.    Sakakibara R, Uchiyama T, Awa Y, et al. Psychogenic urinary dysfunction: a uro-neurological assessment. Neurourol Urodynam. 2007;26(4):516-524.
6.    Bird JR. Psychogenic urinary retention. Psychother Psychosom. 1980;34(1):45-51.
7.    Kumar A, Banerjee GK, Goel MC, et al. Non-neurogenic, non-organic urinary retention in female: An indication for urodynamic evaluation. Indian Jl of Urol. 1996;12(2):55-59.
8.    Wheeler JS, Walter JS. Urinary retention in females: a review. Int Urogynecol J. 1992;3(2):137-142.
9.    Mosli HA, Farsi HM, Rimawi MH, et al. Retention of urine in females: causes and management. East Afr Med J. 1991 68(8):617-623.
10.    Sagar RS, Ahuja N. Psychogenic urinary retention. Am J Psychiatry. 1988;145(9):1176-1177.

 

This interview took place on November 30, 2009 and was conducted by Norman Sussman, MD.

 

Dr. Weintraub is Associate Professor of Psychiatry and Fellow at the Institute of Aging at the University of Pennsylvania in Philadelphia. His areas of research interest include the psychiatric and cognitive complications of Parkinson’s disease. Dr. Weintraub recently completed a 5-year Career Development Award from the National Institute of Mental Health titled “Depression Diagnosis and Treatment in Parkinson Disease.” In addition, he was coordinating investigator for a multi-site, international, industry-sponsored study of the frequency and correlates of impulse control disorders in Parkinson’s disease.

 

What is Parkinson’s Disease and Why Does Dementia with Lewy Bodies (DLB) Tend to get Clustered in with it in Discussions?

Parkinson’s disease is defined by its motor characteristics, whereas DLB is defined primarily by its cognitive and other non-motor deficits.

To meet criteria for idiopathic Parkinson’s disease, a person must have primary motor symptoms, the most common ones being tremor (upper extremity tremor in particular, usually asymmetric at the time of disease onset); bradykinesia, or slowness of movement; stiffness; and, at times, impairments in balance, although that tends to happen later in the course of the illness. Some combination of those types of motor symptoms is what helps patients meet criteria for Parkinson’s disease, often supported by a response to dopamine-replacement therapy.

In contrast, DLB is characterized at disease onset by a dementing illness consisting of impairment in memory and other cognitive abilities. Supporting features include psychotic symptoms, particularly visual hallucinations. Impairments in attention or fluctuations in alertness are also characteristic. Parkinsonism—some of the same features that I mentioned before—is also characteristic of DLB, although the response to dopamine-replacement therapy is typically less in DLB than in Parkinson’s disease.

 

Would it be confusing for a non-neurologist to distinguish between one or the other?

There is the potential for confusion. One main reason is that a fair number of Parkinson’s disease patients, even at the time of illness onset or diagnosis of motor symptoms, are already demonstrating some level of cognitive impairment.

The two can go hand in hand fairly early in the course of either illness, and therefore there is sometimes a blurring between diagnostic categories. Expert opinion is that if there is an established diagnosis of Parkinson’s disease and at least 1 year has gone by before the patient meets criteria for dementia, then the diagnosis is Parkinson’s disease dementia. If that dementia diagnosis either predates the onset of the motor symptoms or comes within the first year of the parkinsonism, then the patient would meet criteria for DLB.

The reason there seems to be so much overlap is that from a neuropathologic standpoint, the illnesses are very similar. The core neuropathology and even the brain regions that are affected appear to significantly overlap between Parkinson’s disease, Parkinson’s disease dementia, and DLB.

 

Compared to a decade ago, is there better understanding of the pathophysiology of Parkinson’s disease and DLB?

There has been some evolution in terms of understanding. One change to highlight over the past 10 years is that the neurotransmitter deficits really are beyond dopamine in Parkinson’s disease. The noradrenergic deficits are probably as significant or close to as significant as the dopaminergic deficits. In addition, serotonergic deficits can be prominent in the illness. However, it appears that all of the brain stem monoamines are affected to some degree in Parkinson’s disease, so it really is more than just a dopamine disorder.

Another prominent neurotransmitter deficit is in acetylcholine. The cholinergic deficits in Parkinson’s disease dementia are greater than in Alzheimer’s disease. Even non-demented Parkinson’s disease patients have significant cholinergic loss, so that probably helps explain the high frequency of cognitive impairments in Parkinson’s disease.

 

Have Anticholinergics been used to treat Parkinson’s Disease?

Yes, and they still are, though less commonly now. They have to be used cautiously in patients who are more likely to suffer the side effects of anticholinergics, which would include older patients or patients with preexisting cognitive impairment. Younger patients who are more intact cognitively still receive those treatments.

 

How Common are Parkinson’s Disease and DLB?

The primary risk factor for Parkinson’s disease and DLB is increasing age. Accurate prevalence and incidence estimates for Parkinson’s disease are hard to come by. The general estimate of Parkinson’s disease in the United States is anywhere between 500,000 and 1 million people. In Western societies, it is the second most common neurodegenerative disease after Alzheimer’s disease.
 

Looking at only the dementia end, DLB is thought to be the second most common dementing illness after Alzheimer’s disease. Part of the problems with the prevalence estimates are the overlapping diagnoses of DLB and Parkinson’s disease, so it is sometimes difficult to disentangle those two groups. Still, those are the general prevalence estimates. Increasing age is the main risk factor; however, compared with Alzheimer’s disease, it is not as uncommon for patients in their thirties, forties, or even fifties, to develop Parkinson’s disease, much more common relatively than in Alzheimer’s disease.

 

When people lose 80% of their neurons they get clinical manifestations of Parkinson’s Disease. Does everybody as they get older lose these neurons? Is it only a matter of time?

Parkinson’s disease is a disorder of aging. It is unclear if the incidence of Parkinson’s disease will peak at a certain age or whether it just continues to go up. All evidence to this point is that it continues to go up with advanced age. A person needs to lose ~80% of the neurons in the substantia nigra before clinically manifesting the motor symptoms of Parkinson’s disease. Another advancement in the past decade has been the work of Professor Heiko Braak and other neuropathologists that have not only staged Alzheimer’s disease, but also showed a staging process for Parkinson’s disease. Clearly, the brain stem changes in the majority of patients occur even before 80% of those neurons are lost in the substantia nigra, which helps explain some of the pre-motor symptoms that can occur. Beyond the substantia nigra in the later stages of the illness, the pathology spreads to cortical areas; by then it really becomes very much a diffuse brain disease.

 

Are there certain non-motor cognitive or psychiatric symptoms in Parkinson’s disease that will present before any movement disturbance is detected?

Yes, there has been significant research conducted in that area in the past decade, both from large European databases where patients are followed prospectively from young adulthood annually, as well as from case-controlled studies. There is now convincing evidence that patients with Parkinson’s disease compared to non-Parkinson patients are more likely to have a lifetime history of either depression or an anxiety disorder in the 5–10-year period, and perhaps even up to 20 years for anxiety, preceding the onset of Parkinson’s disease.
 

Another common psychiatric or non-motor disorder reported to occur prior to Parkinson’s onset is rapid eye movement behavior disorder, which is a parasomnia where patients are able to verbally or physically act out their dreams. This has been reported to occur up to 20 years prior to the onset of Parkinson’s disease. When most of us dream we are in an atonic state; we cannot physically or verbally act out our dreams. This atonia seems to be lost in a fair percentage of Parkinson’s patients, and apparently may be lost prior to the onset of Parkinson’s disease, which is thought to represent a brain stem dysfunction.
 

Other non-motor symptoms that have been reported to occur prior to Parkinson’s disease include impaired smell or olfaction, which is very common in Parkinson’s disease; constipation; and altered sympathetic intervention of the heart. All are testable.
 

What are some of the cognitive symptoms you observe in patients with Parkinson’s disease?

It was taught in the past that Parkinson’s disease patients compared with Alzheimer’s disease patients are less likely to have memory or language deficits and more likely to have deficits in other domains. For patients that have memory deficits, it is less likely to be an encoding deficit, as seen with Alzheimer’s disease, but more of a retrieval deficit, which was thought to reflect more subcortical dysfunction.
 

However, accumulating research has found that Parkinson’s disease patients can have impairments in a range of cognitive domains, including memory, attention, executive abilities, and visual-spatial abilities. This has been one major shift in the perception of the disease.
 

The other major shift is the recognition that, whereas cross-sectional studies have demonstrated that ~30% of Parkinson’s disease patients have dementia, more careful longitudinal studies1,2 have shown that the overwhelming majority of patients with Parkinson’s disease do develop dementia if followed long enough. Early stages of these deficits can be detectable often at the time of diagnosis in 20% of patients. If the clinician asks the right questions and uses appropriate assessment instruments, the disease can be detected early.

 

What kind of visual-spatial disturbances are involved?

A common example would be the judgment of line orientation tests, which is the ability to conceptualize lines in three dimensions, so to speak. However, it can be detectable even at a much simpler level, just with pentagon or clock drawing. Another difficulty for Parkinson’s patients is drawing a cube. The disease can be detected even on simple paper-and-pencil tests.
 

Are some subtle dysfunctions picked up early and more inevitable ones later on?

Yes. Heterogeneity is the one word that I use more than any to describe all the motor and non-motor features of Parkinson’s disease. There is such a range of presentations of Parkinson’s in patients from both a non-motor and a motor standpoint. This is one area where I think our research has failed us to some extent, in that most studies will present means and averages for patients on a particular score or domain; however, the individual presentation of patients is really lost that way. The means really mean less in Parkinson’s disease than how individual patients present.
 

Some patients do have cognitive deficits early on, and others do not for 15 years. Somebody may have a primary memory deficit, while another may have impairment in multiple domains. Presentations are all over the board.
 

Do treatments for psychiatric symptoms and Parkinson’s disease adversely affect each other?

This is a very controversial and complex area. Early in the course of Parkinson’s disease, a de novo case, for example, who has not been treated ever, often would respond with exposure to dopamine-replacement therapies, whether it is levodopa or dopamine agonists. For instance, some patients show improvements in psychomotor speed, attention, and concentration. However, the results are mixed, with some patients or cognitive abilities improving, and others worsening.  Thus, it is difficult to offer a generalization in this regard.
 

As patients advance in the course of their illness, where they age and the pathology becomes more severe, it seems more likely that the medications, if anything, are not beneficial to cognition. Rather, they may be potentially harmful, particularly with higher dosages when patients can become delirious or psychotic, which certainly has an effect on the cognition, as well.
 

Deep brain stimulation (DBS), which is increasingly used as a treatment for Parkinson’s disease, is thought to perhaps impair verbal fluency and some aspects of memory. That may be a complicating effect of that specific treatment. The anticholinergics and amantadine are probably the most notorious medications in terms of worsening cognition.
 

In terms of psychiatric medications, in general the newer antidepressants are thought to be safe and well tolerated from both a motor and cognitive standpoint. Recent studies show benefit for tricyclic antidepressants in Parkinson’s disease.3,4 One concern there, of course, is that with a heavier anticholinergic load, cognition could potentially worsen.
 

It is unclear from a cognitive standpoint whether antipsychotics have deleterious effects on Parkinson’s disease, but certainly there is concern about them worsening motor symptoms in Parkinson’s patients.
 

Finally, the last class of psychiatric medications commonly used is benzodiazepines. These medications must be used very cautiously in Parkinson’s disease patients because common side effects include impaired gait, sedation, and worsening cognition.
 

Are any therapies currently available for Alzheimer’s disease effective in improving cognitive symptoms in patients with Parkinson’s disease and DLB?

The cholinesterase inhibitor rivastigmine actually has Food and Drug Administration approval for the treatment of Parkinson’s disease dementia. This was on the basis of one large European study5 that showed significant, but modest, benefits in the treatment of Parkinson’s disease dementia, similar to what would be present in Alzheimer’s disease patients. A more recent placebo-controlled study6 in patients with both Parkinson’s disease dementia and DLB showed benefit for memantine. Those are really the two large-scale studies that have been positive to date for the treatment of cognitive dysfunction in Parkinson’s disease.
 

Another common non-motor disturbance in Parkinson’s disease is apathy, often in the context of cognitive impairment, but not always. We really do not have good treatments for apathy in the context of any other disorder. We extrapolate what people use in other populations, including the use of stimulants. Clinicians, myself included, may use methylphenidate and dextroamphetamine as a trial for apathy in particular. Bupropion is also used to some extent because of its stimulant-like properties, the reason being that it has some dopamine-enhancing effects, as well.
 

Have there been any meaningful advances in the treatment of the motor symptoms of these disorders in recent years?

The one class that was not available 10 years ago that is readily available now and used as a first-line agent in younger patients particularly are the dopamine agonists. The ones being used now are more selective and better tolerated overall than the older ones. This class of medication has been added to the armamentarium, in addition to levodopa, although levodopa still is the most potent in terms of its motor effects.
 

DBS has been a significant advancement, particularly for patients with more advanced disease, because those patients really had no option previously. Once they developed dyskinesias and other motor fluctuations, they were really at a dead end in terms of treatment. This often can be a successful treatment for patients that enables them to make a significant decrease in their dopamine-replacement therapy. Other fine tuning has been the increased use of catechol-O-methyl transferase inhibitors, that do allow a better management of motor fluctuations in off periods.
 

That being said, I think treatment has not advanced so significantly. I do think patients are better managed overall. Clinicians are able to go deeper into the course of their illness without significant complications compared with previously.

 

Does using these other, more indirect interventions delay some of the secondary complications of taking levodopa, such as the dyskinesias?

Yes. A preferred medication choice in this day and age would be to start with a dopamine agonist, or even for milder symptomatic benefit something like an monoamine oxidase-B inhibitor early in the course of the illness, and to delay the introduction of levodopa as long as possible.

 

Is there anything you would like to add?

One other interesting area for psychiatrists that has come to the forefront recently—and we have been involved in a fair amount of research with this—is impulse control disorders in response to dopamine agonist treatment. Parkinson’s patients can develop compulsive behaviors (the four that have been reported have been gambling, sexual behavior, buying, and eating) in connection with their Parkinson’s treatment. It is quite a problematic disorder, but also an interesting one from a psychiatric standpoint in that the disorder can be essentially induced by these dopaminergic medications. PP

 

References

1.    Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sørensen P. Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Arch Neurol. 2003;60(3):387-392.
2.    Hely MA, Reid WG, Adena MA, Halliday GM, Morris JG. The Sydney multicenter study of Parkinson’s disease: The inevitability of dementia at 20 years. Mov Disord. 2008;23(6):837-844.
3.    Menza M, Dobkin RD, Marin H, et al. A controlled trial of antidepressants in patients with Parkinson’s disease and depression. Neurology. 2009;72(10):886-892.
4.    Devos D, Dujardin K, Poirot I, et al. Comparison of desipramine and citalopram treatments for depression in Parkinson’s disease: a double-blind, randomized, placebo-controlled study. Mov Disord. 2008;23(6):850-857.
5.    Emre M, Aarsland D, Albanese A, et al. Rivastigmine for dementia associated with Parkinson’s disease. N Engl J Med. 2004;351(24):2509-2518.
6.    Aarsland D, Ballard C, Walker Z, et al. Memantine in patients with Parkinson’s disease dementia or dementia with Lewy bodies: a double-blind, placebo-controlled, multicentre trial. Lancet Neurol. 2009;8(7):613-618.

 

Dr. Belleville is professor in the School of Psychology at Université Laval. Dr. Foldes-Busques is research associate at Centre Hospitalier Affilié Universitaire Hôtel-Dieu de Lévis. Dr. Marchand is professor in the Department of Psychology at the Université du Québec à Montréal.

Disclosures: The authors report no affiliation with or financial interest in any organization that may pose a conflict of interest.

Please direct all correspondence to: Geneviève Belleville, PhD, École de Psychologie, Pavillon Félix-Antoine-Savard, Bureau 1334, 2325, rue des Bibliothèques, Québec (Québec), G1V 0A6; Tel: 1-418-656-2131 ext. 4226; Fax: 1-418-656-3646; E-mail: Genevieve.Belleville@psy.ulaval.ca


 

Abstract

Objective: The objective of this article is to describe the characteristics of patients with panic disorder from an emergency department by comparing them to patients with panic disorder from psychiatric settings on panic symptoms, psychiatric comorbidity, and psychological correlates of panic disorder.
Methods: Eighty-four consecutive patients consulting an emergency department with noncardiac chest pain and diagnosed as having panic disorder, and 126 patients with panic disorder seen in two specialized clinics for anxiety disorders, were assessed with validated clinical interview and questionnaires.
Results: Panic disorder patients recruited in the emergency department were older and reported fewer panic symptoms than their psychiatric settings counterparts. They also had less severe agoraphobic cognitions and less sensitivity to anxiety. The two samples displayed similar rates of psychiatric comorbidities and similar rates of suicidal ideation, with 24.3% to 31.3% of panic disorder patients overall having had thoughts of killing themselves.
Discussion: Panic disorder patients encountered in the emergency department tend to report physical, rather than psychological, symptoms of panic. This finding could explain the extremely low rates of panic disorder recognition in the emergency department.
Conclusion: Despite showing less severe panic symptoms, and sometimes no emotional or cognitive signs of fear at all, emergency department patients with panic disorder have elevated rates of psychiatric comorbidities and suicidal ideation and need adequate clinical attention.


Focus Points

• Male patients with panic disorder were more likely to be encountered in the emergency department of a general hospital than in clinics specialized in anxiety disorders.
• Patients with panic disorder from the emergency department displayed less numerous and severe panic symptoms, agoraphobic cognitions, and sensitivity to anxiety than patients with panic disorder from psychiatric settings.
• One-third of panic disorder patients from the emergency department had non-fear panic disorder, a condition characterized by the physical symptoms of panic but the absence of fear, whether of dying, losing control, or going crazy.
• Despite showing less severe symptoms, panic disorder patients from the emergency department had high rates of psychiatric comorbidity, particularly other anxiety disorders and major depressive disorder.
• In the emergency department sample, one panic disorder patient out of four had suicidal ideation within the past 7 days.

 

Introduction

Chest pain is one of the 13 symptoms that may occur during a panic attack. It is the symptom most likely to prompt consultation at an emergency department.1 Accordingly, 17% to 32% of patients who consult an emergency department with chest pain have panic disorder.2-4 However, despite increasing knowledge about panic in the emergency room, panic disorder remains virtually unidentified.2

The discrepancy between the incidence of panic disorder in the emergency department and the emergency department professionals’ failure to detect it raises important questions regarding the clinical profile of panic disorder patients consulting in the emergency department. These patients may present a different profile compared to panic disorder patients encountered in psychiatric settings. Exploratory data have suggested that panic disorder patients from the emergency department are older, are more likely to be male, have less severe panic symptoms, and have lower rates of agoraphobia than their psychiatric counterparts.5 Reports of clinical experiences also suggested that it is likely for people with panic disorder to initially present to their general practitioner or hospital emergency department with a focus on somatic symptoms and concerns.6 These preliminary findings need to be replicated.

Another concern is the proportion of patients in the emergency department that appear to have a subtype of panic disorder, referred to as non-fearful panic disorder (NFPD). This subtype is characterized by no report of either fear of dying or fear of going crazy or losing control during panic attacks.7 In the emergency department of a hospital specialized in cardiology, Fleet and colleagues8 found that 44% of panic disorder patients seeking treatment for chest pain could be categorized as having NFPD. Using the National Comorbidity Survey database, Chen and colleagues9 found that 30% of panic attacks occurred without fear of dying or going crazy. The prevalence of this variant of panic disorder in the emergency department of general hospitals is not known.

The principal objective of the present study is to compare panic disorder patients from the emergency department versus in psychiatric settings on panic symptoms, psychiatric comorbidity, and psychological correlates of panic disorder. Another objective is to identify the proportion of patients displaying NFPD in a sample of panic disorder patients consulting for chest pain in an emergency department of a general hospital.

 

Method

Participants and Procedure

The emergency department sample consisted of “quasi” consecutive patients consulting an emergency department with non-cardiac chest pain. Although efforts were made to approach every patient admitted to the emergency department with a complaint of chest pain on weekdays from 8am to 4pm, several patients (1,101 out of 3,234; 34%) could not be reached for various reasons (as described in the Figure). Inclusion criteria for the study were: ≥18 years of age, French or English speaking, and consulted the emergency department for chest pain non-associated with chest trauma. Exclusion criteria were: presented results outside the normal ranges on the electrocardiogram or blood tests, suggesting coronary artery disease; and presented a clear medical cause for the chest pain (eg, pulmonary embolism). Patients were assessed with self-report questionnaires and a clinical diagnostic interview conducted by a research assistant while they were in medical observation or waiting for tests results. Self-report questionnaires were completed on site or at home and returned to the research team with a prepaid envelope (if patients had insufficient time to complete the forms or if they were too tired). For the purpose of this study, the authors included data from participants meeting criteria for panic disorder based on the Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition.10 Significant interference with at least one area of functioning was defined by a clinical score of ≥4 on the Anxiety Disorder Interview Schedule for DSM-IV (ADIS-IV; n=84).11

 

The psychiatric settings sample was composed of 126 patients recruited for a panic disorder treatment delivered in a specialized anxiety clinic through newspapers and referrals by healthcare professionals. This sample included patients referred by family physicians, general practitioners and psychiatrists working in a psychiatric hospital, and psychiatrists working in a specialized anxiety clinic, as well as self-referred patients. Inclusion criteria were: 18–65 years of age; diagnosis of panic disorder with agoraphobia, based on DSM-IV criteria, for at least 1 year; onset of panic disorder prior to 40 years of age; and had not participated in cognitive-behavioral therapy for panic disorder within the last year. The severity of the disorder for the psychiatric settings sample was moderate to severe, interfering significantly with at least one area of functioning, in accordance with a clinical score of ≥4 on the ADIS-IV, and a score of ≥3 on the Global Assessment of Severity Scale. Following a telephone screening interview, all eligible patients completed an assessment battery and underwent a psychological assessment conducted by a research assistant. Patients were assessed using a clinical interview, and self-report questionnaires were completed before receiving treatment.

 

Measures

The ADIS-IV

The ADIS-IV is a semi-structured interview assessing anxiety disorders according to DSM-IV criteria. It also includes a series of questions targeting mood, somatoform, and substance-related disorders. The ADIS-IV is widely used in research and clinical settings, and is considered a gold standard measure for the assessment of panic and other anxiety disorders.12 The ADIS-IV was used in both samples to screen and assess the severity of panic disorder and comorbid psychiatric diagnoses. A French version of this instrument was used, but no information on its psychometric validation is currently available. In the psychiatric settings sample, participants were also administered the Global Assessment of Severity Scale (GASS).13 The GASS is a clinician-administered five-point scale assessing impairment caused by panic and agoraphobic symptoms within the occupational, social, and recreational spheres.

 

BDI-II

The Beck Depression Inventory, Second Edition (BDI-II),14 includes 21 items that assess symptoms of depression; for each item, four statements describe increasing levels of symptom intensity. The respondent chooses the statement that best reflects his or her state of the last 7 days. The BDI-II has been extensively validated, and good psychometric properties have been reported for the French version used in this study.15 Item #9 (suicidal ideation) was singled out to assess suicidal ideation.

 

The ACQ

The Agoraphobic Cognitions Questionnaire (ACQ)16 measures the presence of 14 catastrophic thoughts related to panic (eg, “I will have a heart attack”; “I am going to go crazy”). Each thought is rated on a scale from one (very rarely) to five (very often). The total score ranges from one to five, and is computed by averaging the scores on the 14 items. Higher scores indicate greater frequency catastrophic thoughts. The French translation of the ACQ has demonstrated good internal consistency (a=.75) and temporal stability (r=.71).17

 

The ASI

Anxiety Sensitivity Index (ASI)18 is a 16-item self-report questionnaire that assesses the way that respondents react to anxious arousal (eg, “It is important to me not to appear nervous”; “Unusual body sensations scare me”; “It scares me when I am nervous”). Each item is rated on a scale from zero (very little) to four (very much). Total score is obtained by summing the scores from each item and ranges from 0–64, with higher scores indicating greater sensitivity to anxiety. Psychometric properties of the French translation17 are adequate (internal consistency: a=.87; temporal stability: r=.91).

 

Data Analyses

A series of statistical analyses were performed to compare the emergency department and psychiatric settings samples. Mean differences on continuous variables (questionnaires scores) were assessed with independent t tests or Analysis of Variance (ANOVA) tests. Frequency differences on dichotomous variables (presence of symptoms and diagnoses) were evaluated with chi square analyses. Each analysis was tested with a .05 a-level. While no corrections were systematically conducted to adjust the a-level for multiple statistical tests, differences associated with a P value inferior to .05, .01, and .001 were distinctly reported. More importantly, effect sizes were computed each time a statistical test was associated with a P value <.05 in order to assess the strength of the association. Effect sizes of mean differences on continuous variables were evaluated using Cohen’s d (.2=small; .5=moderate; .8=large). Significant chi square analyses were followed by the calculation of Cramér’s V, a measure of the strength of the association between two categorical variables. A Cramér’s V between .20 and .25 reflects a moderate strength of association, and between .30 and .35, a strong one.

 

Results

The sociodemographic characteristics of the participants in the emergency department and psychiatric settings samples are presented in Table 1. Significant differences were observed between samples regarding age, proportion of women to men, and level of education achieved. The emergency department sample was nearly equally composed of men and women (47.6% women), while the psychiatric settings sample had a greater proportion of women (77.0%). Patients from emergency department were, on average, 10 years older than patients from psychiatric settings (48.73 and 38.60 years old, respectively), and had a slightly higher level of education. To ensure that the age difference was not an artifact due to different selection criteria (18–65 years of age in the psychiatric settings sample versus ≥18 years of age in the emergency department sample), the comparison was repeated with participants >65 years of age (n = 13) removed from the emergency department sample. Participants in the emergency department sample were still significantly older than those from the psychiatric settings sample (44.48 vs. 38.60, respectively; P<.001).

 

Table 2 presents the frequency of DSM-IV panic attack symptoms reported by patients with panic disorder, ie, rated ≥4 on a zero-to-eight scale during the administration of the ADIS-IV, according to sample of origin. Eleven out of 13 symptoms were more frequently reported by psychiatric settings patients than by emergency department patients. Cramér’s V values ranged from .14 (fear of dying) to .50 (fear of losing control or going crazy), indicating effect sizes of moderate to large magnitude for most differences (Table 2). Only paresthesia was evenly encountered in both groups. Although participants from the emergency department sample consulted for chest pain, they may have reported not having it during panic attacks; thus, most (83.1%), but not every, panic disorder patients from the emergency department reported chest pain. On average, psychiatric settings patients reported three more symptoms during panic attacks than emergency department patients (9.21 vs. 6.61; Table 2).

 

Rates of psychiatric comorbidity among both samples are presented in Table 3. Agoraphobia was encountered in 32.1% of emergency department patients. The high prevalence of agoraphobia in the psychiatric settings sample (100%) only reflected the selection criteria used to recruit this sample. Rates of comorbid anxiety disorders were similar in both groups, with the exceptions of specific phobia and posttraumatic stress disorder (PTSD), which were more frequent among emergency department patients. Mood disorders, particularly major depressive disorder (MDD), were also more frequent among emergency department patients than among psychiatric settings patients (Table 3). Comorbid somatoform or substance-related disorders were rarely encountered in either group.

 

Further differences emerged regarding psychological aspects related to panic disorder (Table 4). Emergency department patients had lower ACQ and ASI scores, indicating less severe agoraphobic cognitions and less sensitivity to anxiety. Corresponding effect sizes were large. To ensure that the difference in ACQ scores was not an artefact due to different selection criteria (only participants in the psychiatric settings sample had to suffer from agoraphobia to be included in the study), the comparison was repeated with participants without agoraphobia (n=57) removed from the emergency department sample. Participants remaining in the emergency department sample still reported significantly lower ACQ scores than those from the psychiatric settings sample (2.019 vs. 2.649, respectively; P<.001). Severity of depressive symptomatology and presence of suicidal ideation were similar in both groups. BDI mean scores indicated the presence of mild depressive symptoms in both groups. Between 24.6% and 31.3% of all panic disorder patients reported suicidal ideation.

 

The characteristics of panic disorder patients that could be categorized as having NFPD, ie, that reported no fear of dying or of losing control during panic attacks, are reported in Table 5. The proportion of NFPD patients in the emergency department sample (32.1%) was almost three times that observed in the psychiatric settings sample (11.9%). In order to assess differences between panic disorder and NFPD while partitioning out the variance attributable to the sample of origin (emergency department or psychiatric settings), three 2X2 ANOVAs were performed, on the ACQ score, the ASI scores, and the number of “non-fear” panic symptoms. Independent variables were “type of panic disorder (panic disorder or NFPD)” and “sample of origin (emergency department or psychiatric settings).” NFPD patients had lower ACQ and ASI scores, as well as fewer panic symptoms. Interactions were not statistically significant, except for the ACQ scores. Inspection of the means indicated that the difference between panic disorder and NFPD patients was more important in the psychiatric settings sample than in the emergency department sample.

 

Discussion

The objective of this study was to compare panic disorder patients from emergency department and psychiatric settings on panic symptoms, psychiatric comorbidity, and psychological correlates of panic disorder. Panic disorder patients recruited in the emergency department were older, reported fewer panic symptoms, and had less severe agoraphobic cognitions and less sensitivity to anxiety than their psychiatric settings counterparts. The two samples displayed similar rates of psychiatric comorbidities, with the exceptions of MDD, specific phobia, and PTSD, which were more frequent among patients from the emergency department. Both samples reported alarmingly high rates of suicidal ideation.

Fleet and colleagues5 compared panic disorder patients from the emergency department of a hospital specialized in cardiology to a sample recruited in psychiatric settings, with results that were very similar to those of the present study. This study’s findings were replicated regarding older age, low prevalence of agoraphobia in the emergency department, and the absence of difference in severity of depressive symptomatology and suicidal ideation. Adding to these findings, the authors observed that panic disorder patients from the emergency department reported fewer symptoms during their attacks, and that NFPD was more frequently encountered in the emergency department.

The reasons for the differences between the clinical portrait of panic disorder patients from the emergency department and panic disorder patients from psychiatric settings are not known. Observed differences may reflect the chronicity of panic disorder symptoms. Onset of panic disorder in psychiatric settings patients occurred at least 1 year prior to the study, while symptoms were present for at least the past month for the emergency department sample. Moreover, one of the most frequently cited reasons for consulting an emergency department during a panic attack is that the panic symptoms are part of a first episode, or that a new or more intense symptom has appeared.1 Panic disorder may develop progressively, with few symptoms during earlier panic attacks and increasing symptoms as the panic experience repeats itself over time. First episodes may lead patients to consult the emergency department because they believe their symptoms to be of organic origin. As they receive multiple negative results from medical exams and accumulate a history of impairment due to panic, patients with recurrent and aggravating panic attacks may be more likely to be directed toward mental health care. Early screening of these patients and referral to appropriate treatment could prevent this progression of symptoms. However, the stigma attached to mental illness may prevent emergency department patients from disclosing emotional symptoms, rendering even more difficult for emergency department physicians to recognize the emotional disorder causing chest pain.

The inclusion of NFPD patients may be an additional explanation for the appearance of less severe symptoms of panic disorder in emergency department patients. NFPD patients displayed genuine panic attacks, without reporting fear of dying or fear of going crazy or losing control. They also displayed less severe agoraphobic cognitions and less sensitivity to anxiety. Although these differences were observed in NFPD patients from psychiatric settings as well as from the emergency department, NFPD patients were nearly three times more likely to be encountered in the emergency department than in psychiatric settings. In fact, nearly one out of three (32.1%) panic disorder patients recruited in the emergency department could be categorized as having NFPD.

One implication of these findings is that, as a result of their less severe symptoms, infrequent manifestations of agoraphobia, less reported overall impairment, and a less “psychiatric” presentation, patients with panic disorder in the emergency room may not be adequately screened and offered appropriate therapeutic options. Indeed, recognition of panic disorder by healthcare providers has been associated with severity of fear experienced during the worse panic attack and overall symptom severity during the panic attack that led to consultation.19 Failure to recognize panic among chest pain patients is associated with serious consequences in terms of phobic avoidance, quality of life, and healthcare utilization.20-22 The current results have indicated that these patients suffer from significant depressive comorbidity, to an even greater degree than psychiatric patients, and that they present an elevated level of depressive symptomatology and suicidal ideation, replicating findings observed in their counterparts from psychiatric settings.21-23 In light of these data, it is essential that panic disorder be adequately identified and addressed and not merely considered as a residual category for noncardiac chest pain of unknown origin.

These findings are to be interpreted with caution as the study includes some methodologic limitations. First, due to the different settings, the selection criteria across both samples were not exactly the same. However, the authors performed statistical analyses on selected subsamples aiming to reduce the likeliness of rival explanations. Another limitation is that the emergency department sample did not include panic disorder patients that did not consult for chest pain (eg, patients consulting for hyperventilation, palpitations). As such, the observed differences may generalize only to panic disorder patients consulting the emergency department for chest pain. However, it has been observed that 91% of panic disorder patients presenting at an emergency department consult initially for chest pain.1 Finally, panic disorder patients without agoraphobia were not originally included in the psychiatric settings sample. This certainly explains the difference in prevalence of agoraphobia between the two samples (100% in psychiatric settings and 32.1% in emergency department). These figures do not reflect the true prevalence of agoraphobia among panic disorder patients in psychiatric settings. However, the fact that <33% of patients with panic disorder recruited in the emergency department reported agoraphobia is noteworthy.

 

Conclusion

This study added to earlier findings in demonstrating that panic disorder encountered in the emergency department presents different clinical characteristics than panic disorder seen in psychiatric settings. Despite reporting fewer and less severe symptoms than their counterparts from psychiatric settings, panic disorder patients consulting the emergency department for noncardiac chest pain presented a wide array of distressing symptoms and psychiatric comorbidities that warrant clinical attention, including suicidal ideation. There is a need for valid and “user-friendly” instruments to help emergency department physicians and nurses, who are not extensively familiar with psychiatric nosologies and subtle diagnostic particularities, to rapidly and efficiently identify panic disorder. Panic disorder is a treatable disorder; the efficacy and efficiency of interventions for panic disorder, whether cognitive-behavioral,24 pharmacologic,25 or a combination of both strategies,26 have been extensively demonstrated. Panic disorder patients could benefit from more sensitive panic disorder detection capacities in the emergency department, as well as a stronger bridge between emergency department healthcare providers and the mental health professionals that possess the therapeutic tools to help panic disorder patients.  PP

 

References

1.    Katerndahl DA. Factors associated with persons with panic attacks seeking medical care. Fam Med. 1990;22(6):462-466.
2.    Fleet RP, Dupuis G, Marchand A, Burelle D, Arsenault A, Beitman BD. Panic disorder in emergency department chest pain patients: prevalence, comorbidity, suicidal ideation, and physician recognition. Am J Med. 1996;101(4):371-380.
3.    Srinivasan K, Joseph W. A study of lifetime prevalence of anxiety and depressive disorders in patients presenting with chest pain to emergency medicine. Gen Hosp Psychiatry. 2004;26(6):470-474.
4.    Wulsin L, Liu T, Storrow A, Evans S, Dewan N, Hamilton C. A randomized, controlled trial of panic disorder treatment initiation in an emergency department chest pain center. Ann Emerg Med. 2002;39(2):139-143.
5.    Fleet RP, Marchand A, Dupuis G, Kaczorowski J, Beitman BD. Comparing emergency department and psychiatric setting patients with panic disorder. Psychosomatics. 1998;39(6):512-518.
6.    Austin D, Blashki G, Barton D, Klein B. Managing panic disorder in general practice. Aust Fam Physician. 2005;34(7):563-571.
7.    Beitman BD, Basha I, Flaker G, DeRosear L, Mukerji V, Lamberti J. Non-fearful panic disorder: panic attacks without fear. Behav Res Ther. 1987;25(6):487-492.
8.    Fleet RP, Martel JP, Lavoie KL, Dupuis G, Beitman BD. Non-fearful panic disorder: a variant of panic in medical patients? Psychosomatics. 2000;41(4):311-320.
9.    Chen J, Tsuchiya M, Kawakami N, Furukawa TA. Non-fearful vs. fearful panic attacks: a general population study from the National Comorbidity Survey. J Affect Disord. 2009;112(1-3):273-278.
10.    Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text rev. Washington, DC: American Psychiatric Association; 2000.
11.    DiNardo PA, Brown TA, Barlow DH. Anxiety Disorders Interview Schedule for DSM-IV (ADIS-IV): Lifetime Version (ADIS-IV-L). San Antonio, TX: Psychological Corporation; 1994.
12.    Shear MK, Maser JD. Standardized assessment for panic disorder research. A conference report. Arch Gen Psychiatry. 1994;51(5):346-354.
13.    Mavissakalian M, Michelson L, Greenwald D, Kornblith S, Greenwald M. Cognitive-behavioral treatment of agoraphobia: paradoxical intention vs self-statement training. Behav Res Ther. 1983;21(1):75-86.
14.    Beck AT, Steer RA, Ball R, Ranieri W. Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 1996;67(3):588-597.
15.    Gauthier J, Morin C, Thériault F, Lawson JS. French adaptation of a self-administered measure of depression severity [French]. Revue Québécoise de Psychologie. 1982;3:13-27.
16.    Chambless DL, Caputo GC, Bright P, Gallagher R. Assessment of fear of fear in agoraphobics: the body sensations questionnaire and the agoraphobic cognitions questionnaire. J Consult Clin Psychol. 1984;52(6):1090-1097.
17.    Stephenson R, Marchand A, Lavallée MC. French-Canadian adaptation of the Agoraphobic Cognitions Questionnaire: cross-cultural validation and gender differences. Scandinavian Journal of Behaviour Therapy. 1999;28(2):58-69.
18.    Reiss S, Peterson RA, Gursky DM, McNally RJ. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav Res Ther. 1986;24(1):1-8.
19.    Katerndahl DA. Predictors and outcomes in people told that they have panic attacks. Depress Anxiety. 2003;17(2):98-100.
20.    Katerndahl DA. Panic plaques: panic disorder & coronary artery disease in patients with chest pain. J Am Board Fam Pract. 2004;17(2):114-126.
21.    Roy-Byrne PP, Stein MB, Russo J, et al. Panic disorder in the primary care setting: comorbidity, disability, service utilization, and treatment. J Clin Psychiatry. 1999;60(7):492-500.
22.    Markowitz JS, Weissman MM, Ouellette R, Lish JD, Klerman GL. Quality of life in panic disorder. Arch Gen Psychiatry. 1989;46(11):984-992.
23.    Weissman MM, Klerman GL, Markowitz JS, Ouellette R. Suicidal ideation and suicide attempts in panic disorder and attacks. N Engl J Med. 1989;321(18):1209-1214.
24.    Otto MW, Deveney C. Cognitive-behavioral therapy and the treatment of panic disorder: efficacy and strategies. J Clin Psychiatry. 2005;66(suppl 4):28-32.
25.    Pollack MH, Doyle AC. Treatment of panic disorder: focus on paroxetine. Psychopharmacol Bull. 2003;37(suppl 1):53-63.
26.    Furukawa TA, Watanabe N, Churchill R. Combined psychotherapy plus antidepressants for panic disorder with or without agoraphobia. Cochrane Database Syst Rev. 2007(1):CD004364.

High Rates of Psychiatric Disorders Found in the Wives of Deployed Soldiers

Active military deployment can be a stressful period for both the family member on active deployment as well as family members at home waiting for a safe return. The mental health status of the wives of active military personnel, including those soldiers that are still at home and those that are deployed, has not frequently been studied.

Alyssa Mansfield, PhD, and colleagues reviewed the electronic medical records of >250,000 female spouses of active duty Army personnel receiving outpatient care between 2003 and 2006. Of the wives studied, ~31% had husbands that were currently home, ~34% were stationed overseas between 1–11 months, and 35% were deployed for >12 months.

Mansfield and colleagues found higher rates of mental health diagnosis in the wives of soldiers who were deployed for >12 months compared to those deployed for shorter periods of time or still stationed at home. The Table provides the adjusted analysis of wives whose husbands were not deployed and whose husbands were deployed between 1–11 months compared to the wives whose husbands were deployed for >12 months. When converting the excess cases to potential patients, Mansfield and colleagues found that the 41.3 excess cases would attribute to 3,474 mental health diagnoses and the 60.7 excess cases would attribute 5,370 mental health diagnoses.

 

Although there are limitations to this study, Mansfield and colleagues believe that this data proves that treatment options and preventive measures not only need to be offered to returning soldiers, but also to all military family members. (N Eng J Med. 2010;362(2):168-170.) –CN

 

Hypertension, White Matter Brain Lesions, and Dementia Risk in Older Women

Older women with hypertension may be at greater risk for abnormal white matter lesions in the brain that can cause dementia. The relationship between hypertension, blood pressure, and blood pressure control with white matter abnormalities in the Women’s Health Initiative (WHI) Memory Study—MRI Trial was studied by Lewis H. Kuller, MD, PhD, at the University of Pittsburgh.

The study’s sample included 1,403 women, ≥65 years of age, from the WHI study. All participants had no dementia at baseline and received blood pressure, cognitive, and magnetic resonance imaging (MRI) assessments.

According to MRI, women receiving hypertension treatment, with blood pressure ≥140/90 mm Hg, had the greatest number of abnormal white matter lesions. Women receiving no hypertension treatment, with blood pressure ≥140/90 mm Hg, had “intermediate” levels of abnormal white lesions. The white matter lesions were more likely to appear in the frontal lobe, compared to the occipital, parietal, or temporal lobes, and baseline blood pressure was strongly associated with white matter lesion volumes.

Previous evidence, combined with the current study, continues to suggest that maintaining health blood pressure levels consistently and sooner in life is the best preventive measure against dementia.

The WHI program is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health. (J Clin Hypertens. Epub Dec. 16, 2009) –LS

 

Sudden Infant Death Syndrome Linked to Lower Levels of Serotonin

Sudden infant death syndrome (SIDS) is the leading cause of postneonatal infant death in the United States. During a critical developmental period, SIDS is speculated to result from abnormalities in brainstem control of autonomic function and breathing. It has been reported that irregularities of serotonin (5-HT) and tryptophan hydroxylase (TPH2) receptor binding in regions of the medulla oblongata have been documented in infant deaths resulting from SIDS.

The hypothesis that SIDS is connected with reductions in tissue levels of 5-HT, TPH2, or both was tested by Jhodie R. Duncan, PhD, and colleagues at the Children’s Hospital Boston and Harvard Medical School in Massachusetts. For biochemical analysis, the study involved 35 infants who had died from SIDS, five infants with acute death from known causes, and five hospitalized infants with chronic hypoxia-ischemia. Through autopsy, tissue samples were obtained and several enzymes, including 5-HT and TPH2, were analyzed and measured.

In the raphé obscurus and the paragigantocellularis lateralis regions of the brain, the researchers found that 5-HT levels were 26% lower in SIDS cases compared with age-adjusted controls. TPH2 levels were 22% lower in the raphé obscurus in the SIDS cases, and 5-HT levels were 55% higher in the raphé obscurus and 126% higher in the paragigantocellularis lateralis in the hospitalized group compared with the SIDS group.

According to the authors, SIDS can be viewed as possibly being caused by a defect in one or more parts of the medullary 5-HT system.

Funding for this research was provided by Children’s Hospital Boston and Harvard Medical School in Massachusetts.  (JAMA. 2010;303(5):430-437). –JV

Psychiatric dispatches is written by Christopher Naccari, Lonnie Stoltzfoos, and Jennifer Verlangieri.


 

Dr. Haq is house officer in the Department of Psychiatry at the University of Michigan in Ann Arbor.

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

Off-label disclosure: This article includes discussion of treatments for insomnia and anxiety disorders in patients with chronic alcohol-use disorders which are not approved by the United States Food and Drug Administration.

Acknowledgments: The author would like to thank Kirk Brower, MD, for his valuable editorial assistance; Michelle Riba, MD, Michael Jibson, MD, PhD, and Theadia Carey, MD, for their support; and Edward Jouney, DO, for his inspiration for this article.

Please direct all correspondence to: Aazaz Haq, MD, Department of Psychiatry, University of Michigan, MCHC F6135, 1500 E Medical Center Drive, Ann Arbor, MI 48109; Tel: 734-764-6875; Fax: 734-936-9116; E-mail: ahaq@med.umich.edu.


 

Abstract

Insomnia and anxiety are frequently encountered problems in patients with chronic alcohol use disorders. The use of benzodiazepines and benzodiazepine-receptor agonists in post-withdrawal patients is discouraged due to their abuse potential and cross-reactivity with alcohol, and clinicians should be aware of what alternate medications are available. For the treatment of insomnia, trazodone, low-dose tricylic antidepressants, gabapentin, and quetiapine can all be used effectively in this population. For common anxiety disorders (panic disorder, generalized anxiety disorder, social anxiety disorder, and posttraumatic stress disorder), selective serotonin reuptake inhibitors, buspirone, venlafaxine, quetiapine, and gabapentin all have varying levels of evidence of efficacy. These medications have their greatest effect when used in conjunction with continued behavioral and other non-pharmacologic therapy.


Focus Points

• Some antidepressants at low doses (trazodone, tricyclic antidepressants), at least one antiepileptic (gabapentin), and atypical antipsychotics (particularly quetiapine) can all be used to treat insomnia in patients with chronic alcohol use disorders.
• For the treatment of common anxiety disorders in alcohol-dependent patients, there is varying degrees of evidence supporting the use of selective serotonin reuptake inhibitors, venlafaxine, buspirone, quetiapine, and gabapentin.
• Large-scale, placebo-controlled trials assessing the efficacy of common anxiolytics in the treatment of anxiety disorders in alcohol-dependent patients are generally lacking.
• Benzodiazepines and benzodiazepine receptor agonists should be used in patients with alcohol-use disorders only with extreme caution.

 

Introduction

Alcohol use disorders are known to be frequently comorbid with insomnia, anxiety, and depression.1,2 While depression can be difficult to treat in alcoholics, the medications used to treat depressive symptoms in this population are no different than those used in the general population.3 In contrast, the treatment of insomnia and anxiety in alcoholic patients is made particularly challenging by the relative contraindication of benzodiazepines in this population due to their abuse liability.4 Clinicians who treat patients with alcohol use disorders should be aware of what options are available to treat insomnia and anxiety.

A significant association between alcohol dependence and insomnia has been shown in several community samples.5,6 Moreover, disturbed sleep has been shown to be a strong predictor of relapse in alcoholics after detoxification,7,8 and alcoholic patients are much more likely to use alcohol to self-medicate for their insomnia.8 During acute withdrawal, alcoholics have short and fragmented sleep with long sleep latencies, very small amounts of delta (stages 3 and 4) sleep, and vivid dreams.9 Sleep continues to be significantly disrupted during the first month of sobriety and slowly improves over the next few months. Some measures of sleep quality remain abnormal at ≥14 months after abstinence, with continued decreased delta-wave sleep, increased rapid eye movement (REM) percentage, and increased REM latency.10

Alcoholism is also frequently comorbid with anxiety disorders. In some patients with a genetic predisposition to an anxiety disorder, ingestion of alcohol can “unmask” anxiety symptoms.11 Other patients with preexisting anxiety disorders frequently use alcohol to self-medicate. The National Comorbidity Study found that in 8,000 respondents with alcohol use disorders in the United States between 15–54 years of age, 37% had at least one anxiety disorder, most commonly social anxiety disorder (18%).12 Independent community studies from Germany and Australia have reported rates of comorbid anxiety disorders among alcoholic patients of 42.3% and 15%, respectively, with the most common disorders being generalized anxiety disorder (GAD) and specific phobia.13,14 Significantly higher degrees of anxiety are found in patients who subsequently relapse within 6 months of initiating abstinence than those who manage to stay sober.15

This article discusses the alternatives to benzodiazepine treatment in the management of insomnia and anxiety in post-withdrawal alcohol-dependent patients. For the treatment of insomnia in these patients, trazodone, tricyclic antidepressants (TCAs), gabapentin, and quetiapine are commonly used. For anxiety disorders, selective serotonin reuptake inhibitors (SSRIs), buspirone, venlafaxine, quetiapine, and gabapentin can all generally be used with efficacy, depending on the specific type of anxiety disorder.

 

Insomnia

Antidepressants

The sedative properties of some antidepressants, typically at low doses, can be used to treat insomnia in alcoholic patients. Trazodone is the second most common medication used by clinicians for insomnia (after zolpidem), despite the relative absence of convincing evidence of its efficacy in non-depressed patients with insomnia.16 It is the agent most commonly used by addiction specialists to treat insomnia in alcoholic patients.17 Trazodone has a relatively benign side-effect profile (most common side effects being drowsiness, dizziness, dry mouth), appears to have few interactions with alcohol,18 and does not have abuse potential.19 Some data suggest that tolerance to the sedative effects of trazodone may develop over long-term use.16 For example, two studies20,21 looking at objective measurements of the sedative effects of trazodone show a slight decrease in the total sleep time in subjects using trazodone after week 3 in one study20 and week 4 in the other.21 However, further studies are needed to clarify this effect.

A small (n=16), double-blind, placebo-controlled study22 assessing the efficacy of trazodone in improving sleep in post-withdrawal alcoholics found that, after 4 weeks, patients receiving nightly trazodone (50 mg/night, titrated up to 200 mg) had significantly increased sleep efficiency, less frequent night-time awakenings, and increased non-REM sleep percentage, than those receiving placebo. A later double-blind, placebo-controlled study19 with a larger sample size (n=173) confirmed that trazodone improves sleep quality and overall mental health during its administration. However, the study19 also found that the patients in the trazodone group had less improvement in the proportion of abstinent days during 3 months of treatment and drank a greater number of drinks per drinking day following the cessation of the medication than the placebo group. Therefore, trazodone was not recommended with confidence for the routine treatment of insomnia in alcohol-dependent patients.

Sedating TCAs can be used at low doses for their anti-histaminergic properties to treat insomnia. For example, doxepin, whose antidepressant effects are typically seen at daily doses of 50–300 mg, has been shown to produce effective hypnotic effects at doses of 1–6 mg/day.23,24 At these low doses, doxepin is selective for blocking only histamine (H)1 receptors and has no effect on serotonin or norepinephrine transporters or muscarininc acetylcholine receptors.25 Selective H1 blockade is not associated with rebound insomnia, loss of hypnotic efficacy over time, or daytime sedation; these undesirable effects of many “antihistamine” medications are largely due to their actions on muscarinic, cholinergic, and adrenergic receptors.25,26 Because muscarinic receptors are not affected at such low doses, the anticholinergic side effects of confusion, dry mouth, blurred vision, constipation, and urinary retention, which are commonly associated with TCAs, are not seen with low dose doxepin. TCAs also have the benefit of not producing euphoria as a side effect, not causing physical tolerance or dependence, and not being controlled substances.23 TCAs should be used with caution in alcohol-dependent patients; even mild overdoses can cause cardiotoxicity or severe orthostatic hypotension and can be fatal, something to be wary of in a population that is at an increased risk for suicide attempts. Moreover, TCAs can lower the seizure threshold, so they should be used with caution in patients undergoing alcohol withdrawal.

SSRIs are generally not used to treat insomnia, as they can frequently worsen sleep and increase the number of nighttime awakenings.24 Nefazodone, an antidepressant with a similar structure to trazodone, has some sleep-promoting properties, but it is rarely used today because of its risk of serious hepatic toxicity.

 

Gabapentin

Gabapentin has recently been gaining favor for the treatment of alcohol dependence and alcohol-related insomnia. Gabapentin is an antiepileptic medication that has a relatively benign side-effect profile, little abuse potential, and does not affect the metabolism or excretion of other medications. Gabapentin has been studied for alcohol-related insomnia during both acute withdrawal and after several weeks of abstinence. During acute withdrawal, gabapentin was shown to be superior to lorazepam in reducing nighttime insomnia and daytime sleepiness among subjects with a history of repeated withdrawal episodes.27 In a preliminary non-blinded, uncontrolled study of post-withdrawal insomnia, Karam-Hage and Brower28 showed that 15 alcohol-dependent patients had improved sleep quality as per the Sleep Problems Questionnaire (SPQ) with an average gabapentin dose of 953 mg/day.

In another non-randomized, non-blinded, uncontrolled study29 (n=50) comparing gabapentin with trazodone for the treatment of post-withdrawal insomnia in patients with alcohol dependence, both medications were shown to improve sleep quality, as per the SPQ, although gabapentin improved sleep quality significantly more than trazodone and was associated with less sedation the next day. However, in a recent double-blind, placebo-controlled pilot trial30 (n=21) of post-withdrawal alcohol-dependent subjects, the same authors found no significant difference in the sleep quality of the gabapentin versus placebo group, as measured by the SPQ, sleep diary parameters, and polysomnography parameters. Of note, gabapentin significantly delayed the onset of relapse to drinking in this study.

 

Quetiapine

Of the typical and atypical antipsychotics, quetiapine is the one most commonly used clinically in patients with alcohol use disorders to reduce cravings and promote sleep. A small-scale retrospective review31 of male alcoholic patients at a Veterans Administration (VA) hospital showed that, in patients with difficulty initiating sleep, quetiapine initiated at a dose of 25–50 mg and titrated up to 200 mg increased the total number of days of abstinence and significantly lowered the rate of hospital admissions. The study did not comment on sleep differences between the two groups. Another retrospective chart review32 of data from patients admitted to a 28-day residential rehabilitation program showed significant improvement in insomnia in alcoholic patients given quetiapine. In an open-label pilot trial33 of 28 dually diagnosed alcoholics, quetiapine significantly decreased middle and late insomnia. A randomized control trial34 by the Department of Veterans Affairs to study the use of quetiapine for insomnia during alcohol abstinence is currently recruiting participants. Of note, the use of quetiapine as a drug of abuse has been rising; it is the antipsychotic most commonly implicated in the literature in case reports of antipsychotic abuse.35 It has several street names, such as “quell,” “Susie-Q,” and “baby heroin.”

 

Anxiety

Any of the common anxiety disorders (panic disorder, GAD, social anxiety disorder, and posttraumatic stress disorder [PTSD]) can be comorbid with alcohol abuse or dependence. Below, evidence regarding treatment will be reviewed by disorder. When assessing these disorders in the context of alcoholism, it is important to distinguish them from transient anxiety states related to alcohol intoxication or withdrawal, as these may improve with abstinence alone. The best way to approach this task is by observation of the patient during a period of abstinence, generally after 3 or 4 weeks of sobriety for patients recovering from chronic alcohol use.36

 

Panic Disorder

Several types of antidepressants, including SSRIs, TCAs, monoamine oxidase inhibitors (MAOIs), and venlafaxine, have been shown to be effective in the treatment of panic disorders in patients without substance use disorders, but they have not been studied systematically for use in patients with alcohol or other substance use disorders. Given the unfavorable side-effect profiles of TCAs and MAOIs, SSRIs and venlafaxine are logical choices among antidepressants for the treatment of panic disorder in patients in remission from alcohol.11 SSRIs have a relatively benign side-effect profile, are safe in overdose, and have little abuse potential. To avoid increased anxiety with the initial activation associated with SSRIs, they should be started at a low dose and titrated upwards slowly. Patients should be monitored for relapse in the 4-to-6-week window it takes for the SSRIs to have an effect. As these medications are metabolized by the liver, lower doses should be used in chronic alcoholic patients who have compromised liver function.37 Venlafaxine, a serotonin-norepinephrine reuptake inhibitor, is approved by the US Food and Drug Administration for the treatment of panic disorder38; however, trials of its use in alcohol-dependent patients are lacking.

Gabapentin may be a novel alternative to SSRIs in the treatment of severe panic disorder. In a double-blind, placebo-controlled study (n=103), gabapentin (dosed from 600–3,600 mg/day) was not found to be more effective than placebo in reducing scores on the Panic and Agoraphobia Scale (PAS).39 However, in the severely ill subset of patients with baseline PAS≥20, the patients treated with gabapentin showed significant improvement in PAS scores. Gabapentin has not been studied for treatment of panic disorder in alcoholic patients; however, it has a favorable risk-benefit profile and may be a good option for alcoholic patients with severe panic symptoms for whom SSRIs or venlafaxine are not good options or are ineffective.

 

GAD

Diagnosis of GAD in patients with substance abuse disorders is challenging, as many symptoms of intoxication and withdrawal, such as anxiety, restlessness, difficulty concentrating, fatigue, and sleep disturbance, are similar to the symptoms of GAD. Of the anxiolytic medications, buspirone has been studied most extensively for treatment of GAD in alcoholic patients.40 This is a generally well-tolerated medication with a favorable side-effect profile (most common side effects being dizziness, nausea, headache, nervousness, lightheadedness, and insomnia). Patients given buspirone (average daily dose 20 mg/day) in a double-blind, placebo-controlled trial41 (n=50) in outpatients with mild-to-moderate alcohol abuse demonstrated decreased scores on the Hamilton Rating Scale for Anxiety (HAM-A) as well as lower discontinuation rate and decreased cravings. In another trial42 evaluating 51 patients with dual diagnoses of alcohol abuse or dependence and GAD, the buspirone treatment group had decreased overall anxiety, less number of days desiring alcohol, and overall clinical global improvement. However, in a double-blinded, placebo-controlled study43 (n=67) of alcohol-dependent patients with high levels of generalized anxiety in a Veteran’s Administration hospital, there was no significant difference on scores between the treatment and placebo groups on the HAM-A or the Speilberger State Anxiety Scale. Lastly, in a randomized, 12-week, placebo-controlled trial,44 buspirone was found to be associated with reduced anxiety, greater retention rate, a slower return to heavy alcohol consumption, and fewer drinks during the follow-up period compared to placebo. Anxiolytic effects with this medication may only be seen at relatively higher doses (above 30 mg/day) after 2–4 weeks of treatment.45

SSRIs, TCAs, venlafaxine, and some anticonvulsants are also effective in treating symptoms of GAD in the general population. However, trials studying these medications in the treatment of GAD specifically in alcoholic patients are lacking. Based on side effects, metabolic profiles, and data from non-alcoholic patients, buspirone, SSRIs, and venlafaxine are likely the most reasonable choices in alcohol-dependent patients for the treatment of GAD.

 

Social Anxiety Disorder

Kessler and colleagues46 found the rate of comorbidity of social anxiety and alcohol abuse to be 22%. Patients with social anxiety disorder often use alcohol to self-medicate and ease anxiety in social situations. In the general population, MAOIs (phenelzine, brofaromine, and moclobemide), SSRIs (sertraline and fluvoxamine), benzodiazepines (clonazepam), and one antiepileptic (gabapentin), have been shown to be effective in treating social anxiety in placebo-controlled trials.47 Buspirone is not effective in treating social anxiety.48 Placebo-controlled trials studying these medications in patients with comorbid alcohol use disorders and social anxiety are lacking, with the exception of one study49 examining the use of paroxetine. In this 8-week, double-blind, placebo-controlled trial (n=18), alcohol-dependent patients in the treatment group (paroxetine titrated to 60 mg/day) showed a significant improvement in social anxiety symptoms (as per the Clinical Global Index and the Liebowitz Social Anxiety Scale) by week 6 of the trial. Of note, no significant difference on any of the quantity/frequency measures of alcohol use was seen between the two groups.

 

PTSD

PTSD is associated with a greatly increased risk of alcohol dependence.50 SSRIs have been widely shown to be successful in the treatment of PTSD in the non-substance-abusing population. In a preliminary open-label trial of sertraline in patients with comorbid alcohol-dependence and PTSD, PTSD symptom scores (per the Impact of Event Scale) and average number of drinks during the follow-up period decreased, while the number of days of abstinence increased.51 In a follow-up randomized, placebo controlled trial (n=94) of sertraline in PTSD patients with comorbid alcohol-use disorders, the same authors52 found a significant decrease in alcohol use in both the treatment and placebo groups. Of note, in this study, a subgroup of patients with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day with sertraline treatment than other groups.

Several atypical antipsychotics, including risperidone,53 olanzapine,54 and quetiapine,55 have been shown to be effective as adjunctive agents to SSRIs in alleviating PTSD symptoms in the general population. However, they have not been studied in patients with co-morbid PTSD and alcohol-use disorders. In a retrospective study31 assessing quetiapine treatment in alcohol-dependent patients in a VA hospital, 90% of whom had PTSD, the authors found a decrease in the number of detoxifications needed per year, increase in the total number of abstinent days, and longer mean time to relapse in patients receiving quetiapine for sleep. These improvements were attributed at least partially to reduction in PTSD symptoms from quetiapine.

 

Benzodiazepines and Benzodiazepine-Receptor Agonists

The use of benzodiazepines in alcoholic patients merits special discussion. These medications are frequently used to treat anxiety and insomnia in the general population. However, except in the treatment of acute alcohol withdrawal, use of these medications in patients with alcohol use disorders is generally discouraged.4 They share a similar mechanism of action on gamma-aminobutyric acid  receptors to alcohol and have a high abuse potential.56 Even in patients without substance use problems, they are generally recommended only for short-term usage and in conservative dosages.57

Benzodiapzepine receptor antagonists (BzRAs), like zolpidem and zaleplon, present an interesting scenario in the treatment of insomnia in alcoholic patients. These medications are generally well tolerated, and studies have shown that they do not cause tolerance or dependence at physiologic doses over short-term (4-week) nightly use58 or long-term (12-week) non-nightly use.59 A very large percentage of patients who use BzRAs for primary nighttime insomnia do not go on to develop dependence or to abuse the drug in the daytime for non-therapeutic reasons.60 In 2002, a systematic review of all published case studies of BzRA dependence found only 36 cases of zolpidem dependence and 22 cases of zoplicone dependence, almost all of which involved former drug or alcohol abusers or patients with other recognized psychiatric disorders.61 This relatively low number of published cases of dependence was in marked contrast to the much higher incidence of dependence known with benzodiazepines. The authors concluded that zolpidem and zoplicone are relatively safe medications, but “extreme caution” should be utilized when prescribing them to patients with a history of substance abuse, dependence, or other psychiatric illness.

It is worth mentioning that withholding benzodiazepines or BzRAs from all post-withdrawal alcoholic patients as a rule may not be an optimal strategy. According to Lejoyeux and colleagues,4 an anxiolytic agent might help to improve the quality of life and adherence to treatment in patients with severe anxiety. A recent prospective study62 monitoring 545 patients with comorbid anxiety and alcohol-use disorder receiving benzodiazepines over 12 years showed that benzodiazepine usage did not predict recovery or relapse. However, the authors were cautious in generalizing their results to all patients or the set of patients who present for addiction treatment. The judicious use of benzodiazepines in a given patient should be decided on a case-by-case basis after a careful assessment of the alternatives as well as the risks and benefits involved.

 

Conclusion

The management of insomnia and anxiety in the alcohol-dependent population can be challenging. With the relative contraindication of benzodiazepines and BzRAs, clinicians have to turn to alternative medications to treat these symptoms. It is important to keep in mind that none of the medications discussed above are FDA-approved for treatment of insomnia or anxiety disorders in alcohol-dependent patients. Moreover, they have their greatest effects when used in conjunction with continued behavioral and non-pharmacologic therapy.63 Continued research is needed to further identify the safety and efficacy of these medications in this unique patient population.  PP

 

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