Corinne Cather

A pilot trial of bupropion added to cognitive behavioral therapy for smoking cessation in schizophrenia.

The purpose of this study was to investigate the effect of adding sustained-release (SR) bupropion to cognitive behavioral therapy (CBT) on smoking behavior and stability of psychiatric symptoms in patients with schizophrenia. We conducted a 3-month, double-blind, placebo-controlled trial of bupropion SR, 150 mg/day, added to a concurrent CBT program with 3-month follow-up in 19 stable outpatients with schizophrenia who wanted to quit smoking. Eighteen subjects completed the trial. Bupropion treatment was associated with significantly greater reduction in smoking, as measured by self-report verified by expired-air carbon monoxide (6/9 subjects, 66%), than placebo (1/9 subjects, 11%) during the 3-month active treatment period and the 3-month follow-up period. One subject in the bupropion group (11%) and no subjects in the placebo group achieved sustained tobacco abstinence for the 6-month trial. Bupropion treatment was associated with improvement in negative symptoms and greater stability of psychotic and depressive symptoms, compared with placebo, during the quit attempt. Subjects in the bupropion group experienced significant weight loss, compared with those on placebo during the smoking cessation attempt. These data suggest that bupropion SR, 150 mg/day, combined with CBT, may facilitate smoking reduction in patients with schizophrenia while stabilizing psychiatric symptoms during a quit attempt.

Extreme Obesity May Be Linked to Markers Flanking the Human OB Gene

Mice with mutations of the ob gene are extremely obese, and the human homologue (OB) has been cloned and physically mapped. The protein product of the ob gene (leptin) reduces body fat in mice when given exogenously, and leptin has been proposed to provide a lipostatic signal that regulates adiposity. Variation in the OB gene may be one genetically determined cause of obesity in human populations. To test this hypothesis, we genotyped siblings from 78 families at markers flanking the human OB gene. Pairs of siblings with extreme obesity (BMI ≥ 40; n = 59) shared haplotypes identical-by-descent for the region containing the OB gene at greater than chance levels (corrected P = 0.04). Furthermore, one haplotype containing the OB gene was transmitted by heterozygous parents to extremely obese (BMI ≥40) offspring more frequently than expected by chance, indicting significant allelic disequilibrium (corrected P = 0.027). One explanation for these linkage findings is that some individuals with extreme obesity have an allelic variant of the OB gene, although other nearby genes could contribute to obesity in these families.

A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia.

Abstract: The objective of this study was to examine the efficacy of bupropion for smoking cessation in patients with schizophrenia. Adults with schizophrenia who smoked more than 10 cigarettes per day and wished to try to quit smoking were recruited from community mental health centers, enrolled in a 12-week group cognitive behavioral therapy intervention, and randomly assigned to receive either bupropion sustained-release 300 mg/d or identical placebo. Fifty-three adults, 25 on bupropion and 28 on placebo, were randomized, completed at least 1 postbaseline assessment and were included in the analysis. The primary outcome measures were 7-day point prevalence abstinence in the week after the quit date (week 4) and at the end of the intervention (week 12). Subjects in the bupropion group were significantly more likely to be abstinent for the week after the quit date (36% [9/25] vs. 7% [2/28], P = 0.016) and at end of the intervention (16% [4/25] vs. 0%, P = 0.043). Subjects in the bupropion group also had a higher rate of 4-week continuous abstinence (weeks 8-12) (16% [4/25] vs. 0%, P = 0.043) and a longer duration of abstinence (4.2 [3.2] weeks vs. 1.8 [0.96] weeks, t = 2.30, P = 0.037). The effect of bupropion did not persist after discontinuation of treatment. Subjects in the bupropion group had no worsening of clinical symptoms and had a trend toward improvement in depressive and negative symptoms. We conclude that bupropion does not worsen clinical symptoms of schizophrenia and is modestly effective for smoking cessation in patients with schizophrenia. The relapse rate is high after treatment discontinuation.

Psychosocial Factors in Outcomes of Heart Surgery: The Impact of Religious Involvement and Depressive Symptoms

This article reports a prospective study of religiousness and recovery from heart surgery. Religiousness and other psychosocial factors were assessed in 142 patients about a week prior to surgery. Those with stronger religious beliefs subsequently had fewer complications and shorter hospital stays, the former effect mediating the latter. Attendance at religious services was unrelated to complications but predicted longer hospitalizations. Prayer was not related to recovery. Depressive symptoms were associated with longer hospital stays. Dispositional optimism, trait hostility, and social support were unrelated to outcomes. Effects of religious beliefs and attendance were stronger among women than men and were independent of biomedical and other psychosocial predictors. These findings encourage further examination of differential health effects of the various elements of religiousness.

A 12-week double-blind, placebo-controlled study of bupropion SR added to high-dose dual nicotine replacement therapy for smoking cessation or reduction in schizophrenia

The objective of this study was to examine whether there is a benefit of adding bupropion SR to high-dose combination nicotine replacement therapy (NRT) and weekly group cognitive behavioral therapy (CBT) for smoking reduction or cessation in schizophrenia. Fifty-one adult smokers with schizophrenia were randomly assigned to a 12-week trial of bupropion SR 300 mg/d or placebo added to transdermal nicotine patch, nicotine polacrilex gum, and CBT. The treatment goal was smoking cessation. The primary outcome measure was biochemically confirmed 7-day point-prevalence of 50% to 100% smoking reduction at week 12. Secondary outcomes were biochemically confirmed tobacco abstinence and change from baseline in expired air carbon monoxide (CO) and psychiatric symptoms. Subjects on bupropion + NRT had a greater rate of 50% to 100% smoking reduction at weeks 12 (60% vs. 31%; P = 0.036) and 24, a lower expired air CO in the treatment and follow-up periods, (F = 13.8; P < 0.001) and a greater continuous abstinence rate at week 8, before NRT taper, (52% vs. 19%; P = 0.014). However, relapse rates in subjects on bupropion + dual NRT were 31% during NRT taper (weeks 8-12) and 77% at the 12-month follow-up. Abstinence rates did not differ by treatment group at weeks 12 (36% vs. 19%), 24 (20% vs. 8%), or 52 (12% vs. 8%). Because abstinence rates were high during treatment with combination pharmacotherapy and relapse rates were very high during taper and after discontinuation of treatment, study of longer term treatment with combination pharmacotherapy and CBT for sustained abstinence is warranted in those who attain initial abstinence with this intervention.

Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: an exploratory study.

BACKGROUND Daily dosing with d-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models, single-dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with d-cycloserine will produce persistent improvements in negative symptoms and cognition. METHODS Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, eight-week add-on trial of d-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of d-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score. RESULTS Thirty-three subjects (87%) completed the trial. d-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with d-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of d-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments. CONCLUSIONS Once-weekly dosing with d-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of d-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with d-cycloserine for the treatment of negative symptoms merits further study, as do d-cycloserine effects on memory consolidation.

A pilot study of functional Cognitive Behavioral Therapy (fCBT) for schizophrenia.

BACKGROUND The feasibility and preliminary efficacy of a novel cognitive behavioral treatment for decreasing psychotic symptoms and improving social functioning was evaluated in a pilot study. This represents the first treatment outcome study of CBT for psychosis with a manualized, active comparison condition. METHODS Thirty outpatients with schizophrenia or schizoaffective disorder, depressed type with residual psychotic symptoms were randomly assigned to either 16 weekly sessions of functional cognitive behavioral therapy (fCBT) or psychoeducation (PE) with assessments conducted at baseline and post-treatment by blind evaluators. RESULTS Attrition was only 7% and did not differ between fCBT and PE, indicating good tolerability of both treatments. For this sample with persistent symptoms, between groups effects were not significantly different, but within group effect sizes indicated greater treatment benefit for fCBT on positive symptoms, particularly for the PSYRATS voices subscale. CONCLUSION The results suggest that fCBT is well tolerated and holds promise for reducing persistent positive symptoms.

An exploratory open-label trial of aripiprazole as an adjuvant to clozapine therapy in chronic schizophrenia

Objective:  We conducted this 6‐week open‐label trial to examine the effects of adjunctive aripiprazole in clozapine‐treated subjects on weight, lipid and glucose metabolism, as well as positive and negative symptoms of schizophrenia.

Dietary Intake Profile of Patients with Schizophrenia

BACKGROUND The increasing prevalence of overweight and obesity has become a priority public health issue in the United States. Forty to 62% of people with schizophrenia are obese or overweight (1, 2). High morbidity and mortality in schizophrenia may be attributed to an unhealthy lifestyle such as poor diet, lack of exercise, smoking, and substance abuse (3). Obesity is associated with greater risk of developing hypertension, type 2 diabetes, coronary heart disease, stroke, death, and reduced quality of life compared with that found in the general population (4, 5). We performed a cross-sectional study evaluating the dietary intake of patients with schizophrenia or schizoaffective disorder treated with atypical antipsychotic agents. METHODS Dietary intake of 88 patients from an urban community mental health clinic was measured using a four-day dietary record. Nutritional variables included total energy intake, fat, protein, carbohydrate, cholesterol, fiber, sucrose, folate, calcium, sodium, zinc, alcohol and caffeine. Data were compared to the general population using data matched for age, gender, and ethnicity from the National Health and Nutrition Examination Survey (NHANES), 1999-2000. RESULTS The Body Mass Index (BMI) of the schizophrenia group (M = 31.3, SD = 12.67) was significantly greater than the NHANES group (M = 28.3, SD = 6.62) (p = .001). The schizophrenia group consumed significantly fewer calories, carbohydrate, protein, total fat, saturated fat, monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), fiber, folate, sodium and alcohol and significantly more caffeine than the NHANES group. CONCLUSIONS The findings may suggest that obesity in schizophrenia patients is not solely related to food consumption, but perhaps other effects including medication side effects and reduced physical activity. Education and interventions for the schizophrenia population should focus more on overall lifestyle factors such as physical activity and healthy food choices.

Aripiprazole added to overweight and obese olanzapine-treated schizophrenia patients.

Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance, and diabetes mellitus. There are few options for olanzapine responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo-controlled, double-blind crossover study that examined 15 mg/d aripiprazoles effects on weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment, there were significant decreases in weight (P = 0.003) and body mass index (P = 0.004) compared with placebo. Total serum cholesterol (P = 0.208), high-density lipoprotein cholesterol (HDL-C; P = 0.99), HDL-2 (P = 0.08), HDL-3 (P = 0.495), and low-density lipoprotein cholesterol (P = 0.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (P = 0.001), total very low-density lipoprotein cholesterol (VLDL-C; P = 0.01), and VLDL-1C and VLDL-2C (P = 0.012) decreased significantly during the aripiprazole treatment phase. The VLDL-3C tended lower during aripiprazole, but the decrease was not significant (P = 0.062). There was a decrease in C-reactive protein comparing aripiprazole treatment to placebo, although it did not reach significance (P = 0.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.