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Serotonin Reuptake Inhibitors May be Associated with Increased Risk of Fracture in the Elderly

In the United States, approximately 10% of elderly primary care patients suffer from major depressive disorder (MDD) and other depressive disorders. Selective serotonin reuptake inhibitors (SSRIs) are the preferred pharmacologic treatment for MDD as they are associated with a lower incidence of adverse effects when compared to other antidepressants. However, a recent study shows a potential link between SSRI use and increased risk of fracture in the elderly population.

J. Brent Richards, MD, of the Division of Endocrinology and Metabolism at McGill University in Montreal, Quebec, and colleagues, evaluated 5,008 community-dwelling adults >50 years of age for 5 years in order to assess the incidence of fractures. Data were gathered on bone mineral density (BMD), falls, and medication use. Researchers also considered additional information, such as patient histories and demographic data, in the final assessment. One-hundred and thirty seven participants (mean age=65.1 years) reported daily use of SSRIs, including citalopram, fluoxetine, fluoxamine, paroxetine, and sertraline.

Richards and colleagues found a two-fold increase in the number of fractures, which most frequently occured in the forearm, ankle, and foot, for these patients. Also, there was a dose-dependent increase in the number of falls among patients using SSRIs daily as well as a decrease in BMD for this group. However, when data were adjusted to account for falls and diminished BMD, there remained a significant correlation between daily use of SSRIs and increased risk of fractures.

“SSRIs were chosen for this study because they have previously been shown to be associated with an increased risk of fracture,” Dr. Richards said. “Previous studies were limited in their ability to control for relevant confounding variables, such as falls and bone mineral density. Our study was novel in that we were able to control for multiple covariates including falls, BMD, and depressive symptoms.”

According to the National Institute of Mental Health, MDD and other depressive disorders affect approximately 26 million people in the US, including approximately 7 million individuals ≥65 years of age. Osteoperosis, a condition that causes brittle bones, is more common among older adults, afflicting >50% of adults >50 years of age. MDD has also been linked to low bone density, which can increase a patient’s risk of fracture, and could mediate study results.

Dr. Richards noted that “the risk attributable to SSRIs was similar to that attributed to corticosteroids, which are most commonly associated with an increased risk of osteoporotic fracture.”

The study authors concluded that clinicians should be aware of risks associated with SSRI use in the elderly population, and consider the association between medication and increased risk of fracture when determining how to treat MDD in elderly patients. Clinicians should also discuss the risks and benefits of using SSRIs with their patients. Richards and colleagues added that elderly patients treated with SSRIs should be encouraged to maintain good physical activity, eat a healthy diet including foods with vitamin D and calcium, and refrain from smoking.

Of note, one limitation of the study was its failure to account for the duration of SSRI use.

Funding for this research was provided by the Alliance for Better Bone Health, the Arthritis Society, the Canadian Institutes of Health Research, The Dairy Farmers of Canada, Eli Lilly, Merck, and Novartis. (Arch Intern Med. 2007;167(2):188-194.) —RS

Inflammatory Markers Incited by Cynic Distrust and Chronic Stress

Prior research has associated psychiatric disorders, such as major depressive disorder (MDD), with markers of artery inflammation, which is associated with greater risk of heart attack and other cardiovascular diseases, including atherosclerosis. However, a recent cross-sectional study found that a much wider range of psychosocial factors can influence the concentration of inflammatory markers.

Nalini Ranjit, PhD, of the Center for Social Epidemiology and Population Health at the University of Michigan in Ann Arbor, and colleagues, evaluated baseline data gathered by the Multi-Ethnic Study of Atherosclerosis (MESA) in order to examine the association between known psychosocial risk factors and cardiovascular diseases. Ranjit and collegues hypothesized that psychosocial risk factors would be positively associated with concentrations of inflammatory markers and analyzed associations between inflammatory markers and psychosocial risk factors. Results were also adjusted for the effect of body mass index (BMI), socioeconomic position, and diabetes.

MESA, a 10-year longitudinal study of 6,814 patients (45–84 years of age), measured cynical distrust, MDD, chronic stress, and the relationship of those factors to CVD. Cynical distrust was measured with an 8-item subset of the Cook-Medley Hostility Scale, depression was measured with the Center for Epidemiologic Studies-Depression Scale (CES-D), and chronic stress was measured with the 4-item Chronic Stress Scale, which measured in the domains of work, finances, and relationships, among others. Blood samples were also used to measure inflammatory markers, including interleukin-6 (IL-6), C-reactive protein, and fibrinogen.

Ranjit and collegues found that high levels of cynical distrust were associated with increased concentrations of inflammatory markers, and results were similar for chronic stress.

“We know that depression is associated with several cardiovascular risk factors,” Dr. Ranjit said. “But finding an association with cynical distrust and chronic stress was very surprising.”

Higher chronic stress levels were equivalent with higher concentrations of IL-6. Although there was no clear evidence of a threshold in the association of psychosocial factors and inflammatory markers, a CES-D score of 21 was associated with higher levels of all three inflammatory markers, however, IL-6 was the only statistically significant difference. After adjustment for behavioral factors, associations of psychosocial factors with inflammatory markers were reduced by 20% to 55%. Adjustment for BMI and diabetes decreased associations by 45% to 100%. The authors reported that, in all cases, associations were reduced after adjustment for behavioral factors.

“The study results suggest that psychosocial factors may act through increasing obesity and unhealthy practices like smoking,” Dr. Ranjit said. “Primary care practitioners should be on the lookout for unhealthy practices among patients with high levels of psychosocial risk factors.”

Funding for this research was provided by the National Heart, Lung, and Blood Institute and the National Institute of Child Health and Human Development. (Arch Intern Med. 2007;167:174-181.) —LS

Cognitive-Behavioral Therapy Demonstrates Efficacy Superior to Other Psychotherapies in Generalized Anxiety Disorder

According to the National Institute of Mental Health, generalized anxiety disorder (GAD), which is characterized by chronic anxiety often due to common or non-existent problems and life situations, affects approximately 6.8 million adults in the United States in a given year. Affecting women more than men, GAD develops gradually and can affect patients of any age. In addition to worry and tension, GAD symptoms can be manifested as physical symptoms, including headaches, trembling and twitching, sweating, fatigue, muscle aches, and irritability, which can lead to reduced quality of life.

While antidepressants have been evaluated in prior studies and shown to be efficacious in GAD treatment, there have been few studies comparing the ability of different psychotherapies to treat the disorder. Vivien Hunot, PhD, of the Institute of Psychiatry in London, England, and colleagues, sought to determine the efficacy of three psychotherapies as treatments for GAD: cognitive-behavioral therapy (CBT), psychodynamic therapy, and supportive therapy.

In reviewing 25 studies with 1,305 patients, Hunot and colleagues compared within the various psychotherapies and against patients on a treatment waiting list or usual treatment. Usual treatment was defined as any appropriate medical care delivered during the study period, including use of medication with or without concurrent therapy. CBT involved patients recognizing destructive thought and reaction patterns and modifying or replacing these patterns with realistic ones, psychodynamic therapy examined patients’ childhood experiences for underlying issues, and supportive therapy utilized patient skills to resolve problems.

Included studies were randomized and quasi-randomized controlled trials conducted in non-inpatient settings that involved adults 18–75 years of age with a primary GAD diagnosis. Treatment response was indicated by anxiety reduction as measured by screening tools of the reviewed studies.

Hunot and colleagues found that patients who received CBT showed the greatest reduction in GAD symptoms over patients receiving other therapies or usual treatment groups. Forty-six percent of patients assigned to CBT showed a response after treatment in contrast to the 14% of patients on a waiting list or receiving usual treatment. Also, patients who completed CBT sessions showed increased reductions in worry, anxiety, and depression symptoms.

“This review provides robust evidence that psychological therapy using a CBT approach is an effective short-term treatment for patients with GAD,” Dr. Hunot said. “The findings may be regarded as highly applicable in primary care practice, since primary care patients tend to prefer psychological therapies to pharmacologic interventions as a treatment for common mental disorders.”

When compared to supportive therapies in six studies, patients receiving CBT showed a non-significant difference in anxiety measures. Hunot and colleagues attribute this finding to the limited number of studies available for comparison, which was not expected by the researchers.

“However, the small number of studies and significant heterogeneity, partly explained by the number of therapy sessions, precludes the ability to draw conclusions on whether or not CBT and supportive therapy are of comparable effectiveness in treating GAD,” Dr. Hunot said. “Given that psychodynamic and supportive therapies are commonly used in primary care clinical practice, the most surprising finding in this review was the lack of currently available evidence to support their use.”

The authors concluded that while CBT is effective when compared to usual treatment, more studies are needed that compare CBT directly to other psychotherapies in the treatment of GAD. Therefore, clinicians should carefully consider utilizing CBT for GAD treatment. Reviewed studies also did not compare CBT to treatment with antidepressants or other medications.

“Naturalistic concurrent prescribing of medications was a common feature of studies included in the review,” Dr. Hunot added. “However, the comparative effectiveness of treatments other than psychological therapies was not investigated.”

Hunot and colleagues also found that patients receiving CBT in group therapy settings had an increased likelihood to dropout of treatment, when compared to patients on a waiting list or those receiving usual care, and GAD patients receiving CBT in individual settings (patient and clinician) were less likely to end treatment. The authors stated that while dropout reasons could have been underreported, the finding may point to a tendency of patients to prefer individual treatment. (Cochrane Database Syst Rev. 2007;(1):CD001848.) —CP

Posttraumatic Stress Disorder Linked to Reported Health Problems in Iraq War Soldiers

Characterized by chronic distressful recollections of traumatic events and psychological upset, posttraumatic stress disorder (PTSD) affects approximately 5 million adults 18–54 years of age in the United States, according to the National Institute of Mental Health, and often occurs comorbid with other anxiety disorders, major depressive disorder (MDD), and substance abuse. While various traumatic events can lead to PTSD—including motor vehicle accidents, natural disasters, child abuse, and witnessing or being involved in a violent crime—warfare and military combat were among the earliest and most prominent causes for PTSD, and were commonly linked to physical health problems for past veterans. Although the ongoing war in Iraq has been identified as a PTSD risk for active soldiers and military personnel, there have been few studies on a potential link between PTSD and physical health problems for these soldiers.

Charles W. Hoge, MD, of the Department of Psychiatry and Behavioral Sciences at the Walter Reed Army Institute of Research in Silver Spring, Maryland, and colleagues, studied PTSD and health problem prevalence in 2,863 soldiers who had returned from combat duty in Iraq 1 year prior to the beginning of the study. Hoge and colleagues sought to find an association between PTSD and increased complaints of health problems by recently returned soldiers.

Study participants, who were from four U.S. Army combat infantry brigades, completed the 17-item National Center for PTSD Checklist, the 9-item Patient Health Questionnaire Depression Scale, and an alcohol screening test. The 15-item Patient Health Questionnaire was also used to evaluate somatic symptoms. Soldiers responded to the standardized self-administered screening measures anonymously, and were also asked the frequency of their sick or missed days at work. Ninety-seven percent of study participants were male, 80% were <30 years of age, 56% were enlisted personnel, and 17% were injured.

Overall, Hoge and colleagues found that 16.6% of study participants met screening criteria for PTSD, as compared to the 5% of soldiers from a comparable group who met PTSD screening criteria prior to their deployment to Iraq. Of the study participants who had been wounded or injured in ≥1 circumstance during their tour, Hoge and colleagues found a 31.8% prevalence of PTSD, as compared to the 13.6% PTSD prevalence for unwounded participants.

Regarding self-reported health measures, the researchers found that soldiers with PTSD had poorer health ratings (47% rated health as poor or fair compared to 20% of soldiers without PTSD), had called in sick or missed days at work ≥2 times in 1 year, had more physical symptoms, and showed higher somatic symptom severity. This finding was also apparent after researchers controlled for combat injuries. Soldiers with PTSD also more frequently reported having sleep problems (71%) as compared to those without PTSD (26%).

The authors concluded that these findings show that PTSD has a close association with the indication of physical symptoms in soldiers 1 year after returning from Iraq, regardless of incidents of injury on duty. Hoge and colleagues suggest that soldiers who have served in Iraq and show symptoms of PTSD, should be evaluated for other physical symptoms and vice versa. Study limitations include a reliance on self-report measures rather than clinician interviews, lack of randomization, and the exclusion of hospitalized soldiers or those in medical care during the study period. (Am J Psychiatry. 2007;164(1):150-153.) —CP

Bipolar Smokers Show Higher Rates of suicide and Psychiatric comorbidity Than Non-Smokers

Previous research has found a higher prevalence of smoking among patients with bipolar disorder compared to the general population. Michael J. Ostacher, MD, MPH, of Massachusetts General Hospital in Boston, and colleagues, reviewed the medical records of 399 outpatients treated at a bipolar specialty clinic over a 5-year span in order to determine the implications of smoking on the disorder.

Ostacher and colleagues evaluated each patient’s records and noted mood state, course of illness, functioning, and psychiatric comorbidities using the Affective Disorders Evaluation and the Mini-International Neuropsychiatric Interview. Their goal was to determine the relationship between smoking, bipolar disorder severity, and suicidal behavior as well as psychiatric and substance use disorder comorbidity.

The authors found that approximately 39% of patients in the study had a history of daily smoking. In addition, bipolar patients who smoked had a greater severity of symptoms, poorer overall functioning, a history of suicide attempts, and lifetime history of comorbid anxiety and substance use disorders. Ostacher and colleagues also found that 47% of bipolar disorder patients who smoked had a lifetime history of a suicide attempt compared to 25% of patients who never smoked. Patients who smoked also had an earlier age of onset of their first depressive and manic episode. A history of comorbid anxiety disorders as well as alcohol and substance abuse and dependence were also found in patients who smoked.

Study limitations included its retrospective nature, that nicotine intake was self-reported rather than diagnosed by a physician, and that researchers had little or no knowledge of factors leading up to the suicide attempts were made.

The authors believe future research is necessary to explore the relationship between smoking, impulsive behavior, and mood. (J Clin Psych. 2006;67(122):1907-1911.) —CN

Psychiatric Dispatches is written by Christopher Naccari, Carlos Perkins, Jr., Lonnie Stoltzfoos, and Rebecca Sussman.