A controlled trial of paroxetine for chronic PTSD, dissociation, and interpersonal problems in mostly minority adults.

This study evaluated the efficacy of paroxetine for symptoms and associated features of chronic posttraumatic stress disorder (PTSD), interpersonal problems, and dissociative symptoms in an urban population of mostly minority adults. Adult outpatients with a primary DSM-IV diagnosis of chronic PTSD received 1 week of single-blind placebo (N = 70). Those not rated as significantly improved were then randomly assigned to placebo (N = 27) or paroxetine (N = 25) for 10 weeks, with a flexible dosage design (maximum 60 mg by week 7). Significantly more patients treated with paroxetine were rated as responders (14/21, 66.7%) on the Clinical Global Impression-Improvement Scale (CGI-I) compared to patients treated with placebo (6/22, 27.3%). Mixed effects models showed greater reductions on the Clinician-Administered PTSD Scale (CAPS) total score (primary plus associated features of PTSD) in the paroxetine versus placebo groups. Paroxetine was also superior to placebo on reduction of dissociative symptoms [Dissociative Experiences Scale (DES) score] and reduction in self-reported interpersonal problems [Inventory of Interpersonal Problems (IIP) score]. In a 12-week maintenance phase, paroxetine response continued to improve, but placebo response did not. Paroxetine was well tolerated and superior to placebo in ameliorating the symptoms of chronic PTSD, associated features of PTSD, dissociative symptoms, and interpersonal problems in the first trial conducted primarily in minority adults.

Are there reliable neuropsychological deficits in obsessive-compulsive disorder?

The aim of this study was to confirm in a large clinical sample that subjects with obsessive-compulsive disorder (OCD) have deficits on certain tasks of executive functioning, non-verbal memory, and/or motor speed. Our ultimate goal was to evaluate whether these deficits contribute to functional impairment and could be the target of a novel treatment intervention. Therefore, in a sample of convenience, the clinical characteristics and neuropsychological performance of adults with OCD and matched healthy controls were evaluated; neuropsychological tasks of executive functioning, non-verbal memory, and motor speed that have shown strong effects in prior studies were used. Primary analyses compared subjects with current OCD only (current-OCD, n=30), subjects with current OCD plus a comorbid disorder (comorbid-OCD, n=15), subjects with a history of OCD (n=15), and matched healthy controls (n=35). Secondary analyses examined whether clinical characteristics (e.g., OCD severity or medication status) were associated with neuropsychological performance. We found no significant overall differences in neuropsychological performance among the four groups. In pairwise comparisons, current-OCD subjects differed significantly from healthy controls only on the Benton Visual Retention Test. OCD severity had little effect and medication status had no effect on neuropsychological performance. In sum, contrary to our expectations, we found few differences in neuropsychological performance between OCD subjects and healthy controls. Whether there are reliable neuropsychological deficits in OCD that can be easily identified in a clinical sample and that contribute to functional impairment remains unclear and requires further study.

Increase in body cell mass and decrease in wasting are associated with increasing potency of antiretroviral therapy for HIV infection.

With the advent of potent combination antiretroviral therapy (ART), there has been a reduction in the incidence of wasting. However, few studies have investigated specific body composition changes associated with these treatments. This study aimed to investigate longitudinally the association of increasingly potent ART with changes in body cell mass and wasting utilizing bioelectric impedance analysis (BIA). In this longitudinal cohort study, 159 HIV-positive men were assessed semiannually from 1995 to 1997 for body composition utilizing BIA, CD4 lymphocyte count, HIV viral load, medical and depressive symptoms. Wasting was defined as body cell mass/height below the 90th percentile based on HIV positive norms. ART potency at each visit was scored utilizing published clinical guidelines, ranging from 1 (0-1 antiretrovirals) to 5 (3 or more antiretrovirals including a potent protease inhibitor). Viral resistance testing was not used. The mixed-effects model and the generalized estimating equations approaches were used to determine longitudinal correlates of body cell mass and of wasting, respectively. Over the 2 years of follow-up, potent combination ART use increased from 6% to 79%. Concurrently, a significant increase in mean body cell mass and a reduction in prevalence of wasting were seen, while total body weight, fat mass, and total body water did not change. Increasingly potent ART was associated with significant increases in body cell mass and reduction in wasting. Other significant correlates of increased body cell mass included higher CD4 count and decreased severity of HIV-related symptoms, fatigue and depression. The current study found that higher potency ART taken for relatively short term (2 years) was associated with an increase in body cell mass and a reduction in wasting and that these changes were associated with both medical (CD4, HIV symptoms) and behavioral (fatigue, depression) improvements. One caveat is this study did not distinguish among types of potent ART regimens. Given only some antiretrovirals appear linked to many body composition changes, regardless of their effect on viral load, it may be the type of regimen used that accounted for the relationship seen between viral load and body composition changes.

Testosterone versus fluoxetine for depression and fatigue in HIV/AIDS: a placebo-controlled trial.

BACKGROUND: While testosterone's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature, no placebo-controlled trial selecting for depressive disorders and including a standard antidepressant has been conducted. Accordingly, this double-blind trial was designed to determine whether testosterone, as well as fluoxetine, is superior to placebo for depression, fatigue, or both. METHOD: One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition depressive disorder entered the 8-week trial and were randomized to testosterone (up to 400 mg IM testosterone cypionate biweekly), fluoxetine (up to 60 mg/d), or double placebo. Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue, the Hamilton Rating Scale for Depression, and the Chalder Fatigue Scale. RESULTS: Ninety men completed the trial. In intention-to-treat analyses, mood response rates were 54%, 47%, and 44% for fluoxetine, testosterone, and placebo, respectively. Among completers, mood response rates were 70%, 57%, and 53%, respectively; in neither analysis were differences between treatments statistically significant. In contrast, testosterone was superior to fluoxetine and placebo for completers regarding fatigue. In intention-to-treat analysis, response rates were 39%, 56%, and 42% for fluoxetine, testosterone, and placebo, respectively, and for study completers, 41%, 63%, and 52%, respectively, (P < 0.05), CONCLUSION: While over 50% of patients treated with testosterone reported improved mood, this rate was not statistically superior to placebo. Thus, our findings do not support prescription of testosterone as a first-line treatment for depressive disorders in HIV-positive men. However, if validated in additional studies, testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression.

Predictors of employment of men with HIV/AIDS: a longitudinal study.

OBJECTIVE: To identify patterns and predictors of work status and number of hours employed in a group of men with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). METHODS: A total of 141 participants had semiannual neuropsychiatric, psychosocial, and medical assessments over a period of 30 months. These six occasions provided the basis for identifying patterns of employment (part-time, full-time, or unemployed). Those who completed neuropsychological testing, introduced at visit 4, constitute the sample used to identify predictors of number of hours employed, using multiple regression analysis with mixed procedure. RESULTS: Over 30 months, 20% were continuously employed full-time, another 9% were continuously employed part-time, and 40% were continuously unemployed. Employment status changed for 31%: 4% who worked at baseline stopped, 13% started or increased their hours, 8% decreased their hours, and 6% showed a fluctuating pattern. The major parameters consistently associated with unemployment or partial employment, in order of influence, were financial (disability benefits), psychiatric (past/current diagnosis of major depression and/or dysthymia), medical (physical limitations), cognitive (executive function), and education. In contrast, age, ethnicity, laboratory markers of HIV illness status, vocational rank, and past or current substance dependence did not predict work status. CONCLUSIONS: Overall, those who worked continued to work. However, despite improved health, most men who were unemployed at study baseline did not return to work. Structure of disability benefits, lifetime depressive disorder, physical limitations, and impairment in some areas of cognitive function each appear to represent significant barriers to work. Returning to work is evidently difficult, and clinicians may keep this in mind when recommending leaving work unless medically necessary. Specific interventions and policy changes regarding disability benefits may be needed to promote return to work for people with HIV/AIDS whose health is restored and who contemplate re-employment.

Citalopram treatment of social anxiety disorder with comorbid major depression.

Treatment of patients with both social anxiety disorder and major depression has been little studied although social anxiety disorder and depression frequently co-occur. Each disorder has been shown to respond to serotonin reuptake inhibitor treatment. Objectives of this study were to characterize a sample of these comorbid patients and to assess response to treatment with citalopram. Patients with primary DSM-IV generalized subtype of social anxiety disorder and comorbid major depression (N = 21) were assessed for symptoms of each disorder, including atypical depressive features, and functional impairment. Patients were treated with a flexible dose of open label citalopram for 12 weeks. Response rates for the intention-to-treat sample at week 12 were 14/21 (66.7%) for social anxiety disorder and 16/21 (76.2%) for depression. All continuous measures of social anxiety, depression, and functional impairment improved significantly with treatment, but depression symptoms responded more rapidly and more completely than social anxiety symptoms. Mean dose of citalopram at study endpoint was 37.6 mg/day. Only three patients (14.3%) fulfilled DSM-IV criteria for atypical features of depression, although 18 (85.7%) fulfilled the criterion for interpersonal rejection sensitivity. Citalopram treatment may benefit patients with primary social anxiety disorder and comorbid major depression, and it should be further studied in controlled trials. Improvement in social anxiety disorder symptoms lagged behind improvement in depression, and greater than 12 weeks of treatment may be required to assess full social anxiety response in patients with comorbid depression. The overlap of social anxiety disorder with atypical features of depression may primarily be due to the shared feature of rejection sensitivity.

Longitudinal improvement in psychomotor processing speed is associated with potent combination antiretroviral therapy in HIV-1 infection.

This longitudinal natural history study aimed to assess the pattern and durability of neurocognitive benefits of progressively more potent combination antiretroviral therapy in HIV-1 infection. A cohort of 141 homosexual or bisexual men were assessed semiannually for CD4 count, HIV RNA viral load, medical and depressive symptoms, and a neuropsychological test battery, including psychomotor speed, verbal memory, and executive function. In a mixed-effects model, increasingly potent antiretroviral therapy was associated with improvement in tests of psychomotor processing speed. This study contributes to the growing literature documenting the longitudinal benefit provided by potent antiretroviral therapy for neuropsychological function, particularly psychomotor processing speed, in patients with HIV illness.

Fluoxetine in children and adolescents with OCD: a placebo-controlled trial.

OBJECTIVE: To examine the safety and efficacy of fluoxetine in child and adolescent obsessive-compulsive disorder (OCD). METHOD: Between 1991 and 1998, 43 patients were randomly assigned to fluoxetine or placebo for 8 weeks. Dosing was fixed for the first 6 weeks (up to 60 mg/day) and then could be increased to 80 mg/day. Responders entered an 8-week maintenance phase. The primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impression-Improvement (CGI-I) scale. Analyses were done on the intent-to-treat sample. RESULTS: Fluoxetine patients (n = 21) had significantly lower CY-BOCS scores than placebo patients (n = 22) after 16 (but not 8) weeks. Fluoxetine responders (n = 11) had significantly lower CY-BOCS scores than placebo responders (n = 7) after an additional 8 weeks of treatment. After 16 weeks, 57% of fluoxetine (versus 27% of placebo) patients were much or very much improved on the CGI-I scale (p <.05). No patient terminated the study because of adverse medication effects. CONCLUSION: Fluoxetine was well tolerated and effective for the treatment of child and adolescent OCD, but fluoxetine's full effect took more than 8 weeks to develop.