Mark H. Pollack

A meta-analysis of treatment outcome for panic disorder

We compared the effectiveness of pharmacological, cognitive-behavioral, and combined pharmacological and cognitive-behavioral treatments in a meta-analysis of 43 controlled studies that included 76 treatment interventions. Cognitive-behavioral treatments yielded the highest mean effect sizes (ES = 0.68) relative to pharmacological (ES = 0.47) and combination treatments (ES = 0.56). In addition, the proportion of subjects who dropped out of cognitive-behavioral treatments was 5.6% relative to 19.8% in pharmacological treatments and 22.0% in combined treatments. Among cognitive-behavioral treatments, those studies that combined cognitive restructuring with interoceptive exposure yielded the strongest effect sizes (ES = 0.88). With regard to pharmacological treatments, there was no significant difference between antidepressants (ES = 0.55) and benzodiazepines (ES = 0.40). Long-term outcome analyses suggested that cognitive-behavioral interventions were the most successful at maintaining treatment gains. Cost analyses indicated that the lowest cost interventions were imipramine treatment and group cognitive-behavioral therapy. In general, cognitive-behavioral treatments yielded the largest effects sizes and the smallest attrition rates relative to pharmacotherapy and combined treatments, and are cost-effective.

Telomere Shortening and Mood Disorders: Preliminary Support for a Chronic Stress Model of Accelerated Aging

BACKGROUND Little is known about the biological mechanisms underlying the excess medical morbidity and mortality associated with mood disorders. Substantial evidence supports abnormalities in stress-related biological systems in depression. Accelerated telomere shortening may reflect stress-related oxidative damage to cells and accelerated aging, and severe psychosocial stress has been linked to telomere shortening. We propose that chronic stress associated with mood disorders may contribute to excess vulnerability for diseases of aging such as cardiovascular disease and possibly some cancers through accelerated organismal aging. METHODS Telomere length was measured by Southern Analysis in 44 individuals with chronic mood disorders and 44 nonpsychiatrically ill age-matched control subjects. RESULTS Telomere length was significantly shorter in those with mood disorders, representing as much as 10 years of accelerated aging. CONCLUSIONS These results provide preliminary evidence that mood disorders are associated with accelerated aging and may suggest a novel mechanism for mood disorder-associated morbidity and mortality.

Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: A preliminary meta-analysis

This study provides a meta-analytic review of controlled trials examining cognitive behavior therapy (CBT) and pharmacotherapy for generalized anxiety disorder (GAD). Thirty-five studies, published or presented between 1974 and January 1996, were identified, and provided 61 separate treatment interventions. Both modalities of treatment offered clear efficacy to patients, and the overall effect size (ES) for CBT (ES = .70) was not statistically different from pharmacotherapy (ES = 0.60) for measures of anxiety severity. CBT was associated with significantly greater effects on depression severity, and was associated with clear maintenance of treatment gains, whereas the long-term efficacy of pharmacologic treatment was attenuated following medication discontinuation. Data concerning the efficacy of specific cognitive behavioral and pharmacologic interventions are provided, as are analyses of the influence of methodological factors (e.g., gender distribution, length of treatment) on the efficacy of treatments.

Placebo-controlled study of gabapentin treatment of panic disorder.

A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate the efficacy and safety of gabapentin in relieving the symptoms of panic disorder. One hundred three patients were randomly assigned to receive double-blind treatment with either gabapentin (dosed flexibly between 600 and 3,600 mg/day) or placebo for 8 weeks. No overall drug/placebo difference was observed in scores on the Panic and Agoraphobia Scale (PAS) (p = 0.606). A post hoc analysis was used to evaluate the more severely ill patients as defined by the primary outcome measure (PAS score > or = 20). In this population, the gabapentin-treated patients showed significant improvement in the PAS change score (p = 0.04). In patients with a PAS score of 20 or greater, women showed a greater response than men regardless of treatment. Adverse events were consistent with the known side effect profile of gabapentin and included somnolence, headache, and dizziness. One patient experienced a serious adverse event during the study. No deaths were reported. The results of this study suggest that gabapentin may have anxiolytic effects in more severely ill patients with panic disorder.

Broad spectrum of cytokine abnormalities in panic disorder and posttraumatic stress disorder

Background: Proinflammatory cytokines have been reported to be elevated in individuals experiencing chronic stress as well as in those with major depressive disorder. Much less is known about cytokines in anxiety disorders such as posttraumatic stress disorder (PTSD) and panic disorder (PD). We hypothesized that PD and PTSD would be associated with a generalized proinflammatory cytokine signature. Method: We utilized Luminex technology to examine 20 cytokines and chemokines in serum from 48 well‐characterized individuals with a primary DSM‐IV PD or PTSD diagnosis, and 48 age‐ and gender‐matched healthy controls. We conservatively employed a Bonferroni correction for multiple testing (α=.05/20=.0025). Results: Individuals with primary PTSD or PD had significantly elevated median peripheral cytokine levels for 18 of 20 different cytokines compared to age‐ and gender‐matched healthy controls (all P<.0025). To assess for the presence of a generalized proinflammatory state, we also examined the proportion of subjects with detectable levels of at least six of nine common proinflammatory cytokines and chemokines (IL‐6, IL‐1α, IL‐1β, IL‐8, MCP‐1, MIP‐1α, Eotaxin, GM‐CSF, and IFN‐α). For men and women, 87% of anxiety patients had six or more detectable levels of these proinflammatory cytokines, compared with only 25% of controls (Fishers Exact Test (FET) P=.000). Confirmatory analysis of the subset of individuals without current psychiatric medication use or comorbid depression was of comparable significance. Conclusions: These findings suggest that a generalized inflammatory state may be present in individuals with PD or PTSD. Depression and Anxiety, 2009.

Clinical and Diagnostic Implications of Lifetime Attention-Deficit/Hyperactivity Disorder Comorbidity in Adults with Bipolar Disorder: Data from the First 1000 STEP-BD Participants

BACKGROUND Systematic studies of children and adolescents with a diagnosis of bipolar disorder show that rates of attention-deficit/hyperactivity disorder (ADHD) range from 60% to 90%, but the prevalence and implications of ADHD in adults with bipolar disorder are less clear. METHODS The first consecutive 1000 adults with bipolar disorder enrolled in the National Institute of Mental Healths Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were assessed for lifetime ADHD. The retrospective course of bipolar disorder, current mood state, and prevalence of other comorbid psychiatric diagnoses were compared for the groups with and without lifetime comorbid ADHD. RESULTS The overall lifetime prevalence of comorbid ADHD in this large cohort of bipolar patients was 9.5% (95% confidence interval 7.6%-11.4%); 14.7% of male patients and 5.8% of female patients with bipolar disorder had lifetime ADHD. Patients with bipolar disorder and ADHD had the onset of their mood disorder approximately 5 years earlier. After adjusting for age of onset, those with ADHD comorbidity had shorter periods of wellness and were more frequently depressed. We found that patients with bipolar disorder comorbid with ADHD had a greater number of other comorbid psychiatric diagnoses compared with those without comorbid ADHD, with substantially higher rates of several anxiety disorders and alcohol and substance abuse and dependence. CONCLUSIONS Lifetime ADHD is a frequent comorbid condition in adults with bipolar disorder, associated with a worse course of bipolar disorder and greater burden of other psychiatric comorbid conditions. Studies are needed that focus on the efficacy and safety of treating ADHD comorbid with bipolar disorder.

A Detailed Examination of Cytokine Abnormalities in Major Depressive Disorder

Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). Twenty cytokines were simultaneously assessed in 49 individuals with MDD and 49 age and gender matched controls. Multiple pro-inflammatory and two anti-inflammatory cytokines were significantly elevated in the MDD sample, including an antidepressant naïve subset. These data support a generalized chronic inflammatory state in MDD, and implicate additional cytokines and chemokines previously linked to cardiovascular disease.

Efficacy of the Novel Anxiolytic Pregabalin in Social Anxiety Disorder: A Placebo-Controlled, Multicenter Study

Abstract: Pregabalin is a novel compound in the development for the treatment of anxiety disorders. The safety and efficacy of pregabalin for the treatment of social anxiety disorder was evaluated in a double-blind, multicenter clinical trial in which 135 patients were randomized to 10 weeks of double-blind treatment with either pregabalin 150 mg/d, pregabalin 600 mg/d, or placebo. The primary efficacy parameter was change from baseline to end point in the Liebowitz Social Anxiety Scale (LSAS) total score. Safety was assessed through clinical and laboratory monitoring, and recording spontaneously reported adverse events. Ninety-four patients (70%) completed the 11-week double-blind treatment phase. LSAS total score was significantly decreased by pregabalin 600 mg/d treatment compared with placebo (P = 0.024, analysis of covariance). Significant differences (P ≤ 0.05) between pregabalin 600 mg/d and placebo were seen on several secondary measures including the LSAS subscales of total fear, total avoidance, social fear, and social avoidance, and the Brief Social Phobia Scale fear subscale. Pregabalin 150 mg/d was not significantly better than placebo on any measures. Somnolence and dizziness were the most frequently occurring adverse events among patients receiving pregabalin 600 mg/d. In conclusion, pregabalin 600 mg/d was an effective and well-tolerated treatment of social anxiety disorder.

Treatment of pharmacotherapy-refractory posttraumatic stress disorder among Cambodian refugees: a pilot study of combination treatment with cognitive-behavior therapy vs sertraline alone.

Cambodian refugees with posttraumatic stress disorder (PTSD) represent a cohort in severe need of treatment, but little information is available to guide treatment choices. We selected a sample of pharmacotherapy-refractory individuals to test the efficacy of combination treatment with sertraline and cognitive-behavior therapy (CBT) for treating PTSD. Participants in this pilot study were ten Khmer-speaking women who had been at a mean age of 22-26 years during the Pol Pot period (1975-1979). These patients were randomly assigned to either sertraline alone or combined treatment. We found that combined treatment offered additional benefit in the range of medium to large effect sizes for PTSD and associated symptoms. Our findings indicate that substantial gains can be achieved by adding CBT to pharmacotherapy for PTSD, and that a program of CBT emphasizing information, exposure, and cognitive-restructuring can be successfully modified for Khmer-speaking refugees.

Moclobemide in social phobia: A controlled dose-response trial

Although the monoamine oxidase inhibitor phenelzine has proven efficacious in social phobia, the risk of hypertensive crises has reduced its acceptability. The reversible monoamine oxidase inhibitor moclobemide has less potential for such reactions, but its efficacy in this disorder remains unproven. A double-blind, placebo-controlled study was undertaken to assess the efficacy and safety of fixed doses of moclobemide. After a 1-week placebo run-in, subjects with social phobia were randomly assigned to placebo or one of five doses (75 mg, 150 mg, 300 mg, 600 mg, or 900 mg daily) of moclobemide for 12 weeks. Although a trend toward greater efficacy of higher doses of moclobemide was observed at 8 weeks, no differences in response to various doses of the drug and placebo were observed at 12 weeks. At 12 weeks, 35% of subjects on 900 mg of moclobemide and 33% of those on placebo were at least much improved. Moclobemide was well tolerated, insomnia being the only dose-related adverse event observed with the drug. In this dose-response trial, moclobemide did not demonstrate efficacy at 12 weeks. Some other controlled studies have found moclobemide and brofaromine, another reversible monoamine oxidase inhibitor, efficacious in social phobia. Possible reasons for inconsistent findings are discussed.