The effects of transdermal nicotine on cognition in nonsmokers with schizophrenia and nonpsychiatric controls.

Abundant evidence indicates that the neuronal nicotinic acetylcholine receptor (nAChR) system is integral to regulation of attentional processes and is dysregulated in schizophrenia. Nicotinic agonists may have potential for the treatment of cognitive impairment in this disease. This study investigated the effects of transdermal nicotine on attention in individuals with schizophrenia (n=28) and healthy controls (n=32). All participants were nonsmokers in order to eliminate confounding effects of nicotine withdrawal and reinstatement that may occur in the study of smokers. Subjects received 14 mg transdermal nicotine and identical placebo in a randomized, placebo-controlled, crossover design. A cognitive battery was conducted before and 3 h after each patch application. The primary outcome measure was performance on the Continuous Performance Test Identical Pairs (CPT-IP) Version. Nicotine significantly improved the performance on the CPT-IP as measured by hit reaction time, hit reaction time standard deviation and random errors in both groups. In addition, nicotine reduced commission errors on the CPT-IP and improved the performance on a Card Stroop task to a greater extent in those with schizophrenia vs controls. In summary, nicotine improved attentional performance in both groups and was associated with greater improvements in inhibition of impulsive responses in subjects with schizophrenia. These results confirm previous findings that a single dose of nicotine improves attention and suggest that nicotine may specifically improve response inhibition in nonsmokers with schizophrenia.

High-dose galantamine augmentation inferior to placebo on attention, inhibitory control and working memory performance in nonsmokers with schizophrenia.

Dysfunction in the neuronal nicotinic acetylcholine receptor (nAChR) system has been implicated in the pathophysiology of schizophrenia, and it has been postulated that treatments that increase nAChR activity may improve symptoms of the disorder. We investigated the effects of the acetylcholinesterase inhibitor and allosteric nAChR modulator, galantamine, on cognitive performance and clinical symptoms when added to a stable antipsychotic medication regimen in nonsmoking outpatients with schizophrenia in a double-blind, placebo-controlled, parallel-group design. Participants were randomized to receive either galantamine (n=10) up to 32 mg/day or identical placebo (n=10) for 8 weeks and completed a cognitive battery at baseline and week 8 and clinical scales at baseline, week 4 and week 8. The primary outcome measure was attentional performance as measured by the d' measure in the Continuous Performance Test - Identical Pairs (CPT-IP) Version. Contrary to our hypothesis, galantamine treatment was associated with inferior performance on the CPT-IP, on the three-card Stroop task, and on the Letter-Number Span task without reordering. Galantamine had no effect on clinical symptoms. In summary, galantamine treatment, at a dose of 32 mg/day, was well tolerated but was not effective as an adjunctive treatment for cognitive deficits in stable nonsmokers with schizophrenia.

A controlled trial of bupropion added to nicotine patch and behavioral therapy for smoking cessation in adults with unipolar depressive disorders.

Although there is a strong relationship between depression and smoking, most nicotine dependence treatment trials exclude depressed smokers. Our objective was to determine whether bupropion improves abstinence rates and abstinence-associated depressive symptoms when added to transdermal nicotine replacement therapy (NRT) and group cognitive behavioral therapy (CBT) in smokers with unipolar depressive disorder (UDD). Adult smokers with current (n = 90) or past (n = 109) UDD were randomly assigned to receive bupropion or placebo added to NRT and CBT for 13 weeks. In the primary analysis, with dropouts considered smokers, 36% (35/97) of those on bupropion and 31% (32/102) on placebo attained biochemically validated 7-day point prevalence abstinence at end of treatment (not significant). Because of a high dropout rate (50%) and a significant difference in abstinence status at dropout by treatment group, a traditional intent-to-treat analysis with last observation carried forward imputation of abstinence status was performed. In this secondary analysis, 56% (54/97) of those on bupropion and 41% (42/102) on placebo met criteria for abstinence at end of trial, chi2 = 4.18, P = 0.04. Nicotine replacement therapy usage and absence of a comorbid anxiety disorder predicted abstinence. Abstinence was associated with increased depressive symptoms, regardless of bupropion treatment. Thus, in the primary analysis, bupropion neither increased the efficacy of intensive group CBT and NRT for smoking cessation in smokers with UDD nor prevented abstinence-associated depressive symptoms. Bupropion seemed to provide an advantage for smoking cessation for those who remained in the trial. The dropout rate was high and was characterized by a higher prevalence of current comorbid anxiety disorder. Given the high abstinence rate achieved with CBT plus NRT, a ceiling effect related to the high level of intervention received by all subjects may have prevented an adequate test of bupropion.

Risperidone augmentation for schizophrenia partially responsive to clozapine: a double-blind, placebo-controlled trial.

RATIONALE: Risperidone augmentation of clozapine in refractory schizophrenia has theoretical but only inconsistent support from clinical trials. OBJECTIVES: To examine if adding risperidone to stable yet symptomatic schizophrenia outpatients on optimized clozapine monotherapy improves psychopathology. METHODS: We conducted a double-blind placebo-controlled parallel-group trial of a fixed dose of 4 mg/day risperidone added for 6 weeks in 24 outpatients with schizophrenia. RESULTS: Subjects who received risperidone showed a non-significant decrease in PANSS total score. The PANSS disorganized thought subscale improved significantly (beta=-3.3079, p=0.047). CONCLUSIONS: Our trial does not support the routine addition of risperidone to clozapine in refractory schizophrenia patients. However, much larger trials are needed to conclusively settle the question of added efficacy from this combination.

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia.

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.

Childhood antecedents of avoidant personality disorder: a retrospective study.

OBJECTIVE: To explore potential risk factors and early manifestations of avoidant personality disorder (AVPD) by examining retrospective reports of social functioning and adverse childhood experiences. METHOD: Early social functioning and pathological childhood experiences were assessed using the Childhood Experiences Questionnaire-Revised. The responses of 146 adults diagnosed with primary AVPD were compared with a group of 371 patients with other personality disorders as a primary diagnosis and a group of 83 patients with current major depression disorder and no personality disorders, using chi2 analyses. Diagnoses were based on semistructured interviews by trained reliable clinicians. RESULTS: Adults with AVPD reported poorer child and adolescent athletic performance, less involvement in hobbies during adolescence, and less adolescent popularity than the depressed comparison group and the other personality disorder group. Reported rates of physical and emotional abuse were higher than the depressed group, but this result was influenced by comorbid diagnoses. CONCLUSIONS: These results suggest that early manifestations of AVPD are present in childhood but that various forms of abuse are not specific to the disorder.

Brain reactivity to smoking cues prior to smoking cessation predicts ability to maintain tobacco abstinence.

BACKGROUND: Developing the means to identify smokers at high risk for relapse could advance relapse prevention therapy. We hypothesized that functional magnetic resonance imaging (fMRI) reactivity to smoking-related cues, measured before a quit attempt, could identify smokers with heightened relapse vulnerability. METHODS: Before quitting smoking, 21 nicotine-dependent women underwent fMRI during which smoking-related and neutral images were shown. These smokers also were tested for possible attentional biases to smoking-related words using a computerized emotional Stroop (ES) task previously found to predict relapse. Smokers then made a quit attempt and were grouped based on outcomes (abstinence vs. slip: smoking > or = 1 cigarette after attaining abstinence). Prequit fMRI and ES measurements in these groups were compared. RESULTS: Slip subjects had heightened fMRI reactivity to smoking-related images in brain regions implicated in emotion, interoceptive awareness, and motor planning and execution. Insula and dorsal anterior cingulate cortex (dACC) reactivity induced by smoking images correlated with an attentional bias to smoking-related words. A discriminant analysis of ES and fMRI data predicted outcomes with 79% accuracy. Additionally, smokers who slipped had decreased fMRI functional connectivity between an insula-containing network and brain regions involved in cognitive control, including the dACC and dorsal lateral prefrontal cortex, possibly reflecting reduced top-down control of cue-induced emotions. CONCLUSIONS: These findings suggest that the insula and dACC are important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment, improve tobacco-dependence treatment outcomes, and reduce smoking-related morbidity and mortality.

A placebo-controlled study of sildenafil effects on cognition in schizophrenia.

BACKGROUND: Phosphodiesterase 5 (PDE5) inhibitors increase cyclic guanosine monophosphate (cGMP) concentrations in the intracellular pathway activated by N-methyl-D-aspartic acid receptors which is believed to mediate long-term potentiation and memory consolidation. The PDE5 inhibitor sildenafil has been shown to enhance memory in animal models. In addition, neuronal nitric oxide synthase, another component of the NMDA/nitric oxide/cGMP intracellular pathway, has been reported to be dysregulated in schizophrenia patients. MATERIALS AND METHODS: Seventeen adult schizophrenia outpatients treated with a stable dose of antipsychotic received a single oral dose of placebo, sildenafil 50 mg, and sildenafil 100 mg in random order with a 48-h interval between administrations. Psychiatric symptom ratings and a cognitive battery were performed at baseline and 1 hour following each administration of the study drug. In addition, memory consolidation was examined by testing recall 48 h later, prior to the next administration of the study drug. RESULTS: Fifteen subjects completed all three treatment conditions. One subject developed irritability and required hospitalization 2 days after receiving sildenafil 100 mg. Neither dose of sildenafil significantly affected cognitive performance or symptom ratings compared to the placebo. CONCLUSION: Despite evidence for cognitive-enhancing effects of sildenafil in animal models, the strategy for treating putative NMDA receptor-mediated memory deficits in schizophrenia with sildenafil 50 and 100 mg was not successful. It is possible that the doses used in this study were not optimal or that repeated dosing may be necessary to achieve therapeutic effects. Agents under development that inhibit other subtypes of PDE remain promising for schizophrenia and dementia.

Prevalence and predictors of posttraumatic stress disorder and depression in HIV-infected and at-risk Rwandan women.

OBJECTIVE: During the 1994 Rwandan genocide, rape was used as a weapon of war to transmit HIV. This study measures trauma experiences of Rwandan women and identifies predictors associated with posttraumatic stress disorder (PTSD) and depressive symptoms. METHODS: The Rwandan Women's Interassociation Study and Assessment (RWISA) is a prospective observational cohort study designed to assess effectiveness and toxicity of antiretroviral therapy in HIV-infected Rwandan women. In 2005, a Rwandan-adapted Harvard Trauma Questionnaire (HTQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess genocide trauma events and prevalence of PTSD (HTQ mean > 2) and depressive symptoms (CES-D > or = 16) for 850 women (658 HIV-positive and 192 HIV-negative). RESULTS: PTSD was common in HIV-positive (58%) and HIV-negative women (66%) (p = 0.05). Women with HIV had a higher prevalence of depressive symptoms than HIV-negative women (81% vs. 65%, p < 0.0001). Independent predictors for increased PTSD were experiencing more genocide-related trauma events and having more depressive symptoms. Independent predictors for increased depressive symptoms were making < $18 a month, HIV infection (and, among HIV-positive women, having lower CD4 cell counts), a history of genocidal rape, and having more PTSD symptoms. CONCLUSIONS: The prevalence of PTSD and depressive symptoms is high in women in the RWISA cohort. Four of five HIV-infected women had depressive symptoms, with highest rates among women with CD4 cell counts < 200. In addition to treatment with antiretroviral therapy, economic empowerment and identification and treatment of depression and PTSD may reduce morbidity and mortality among women in postconflict countries.

A single dose of nicotine enhances reward responsiveness in nonsmokers: implications for development of dependence.

BACKGROUND: Tobacco smoking, driven by the addictive properties of nicotine, is the most prevalent preventable cause of death in the Western world. Accumulated evidence suggests that nicotine may increase appetitive responding for nondrug incentives in the environment. METHODS: To test this hypothesis, we conducted a randomized, double-blind, placebo-controlled, crossover study of the effect of a single dose of transdermal nicotine on reward responsiveness in 30 psychiatrically healthy nonsmokers. A novel signal detection task in which correct responses were differentially rewarded in a 3:1 ratio was used to assess the extent to which participants modulated their behavior as a function of reward. RESULTS: Despite expected adverse effects such as nausea, nicotine significantly increased response bias toward the more frequently rewarded condition, at the expense of accuracy, independent of effects on attention or overall vigilance. Additionally, response bias on placebo was greater in participants who received nicotine in the first session, indicating that an effect of nicotine on reward responsiveness or reward-based learning persisted for at least 1 week. CONCLUSIONS: These findings suggest that a single dose of nicotine enhances response to non-drug-related rewards in the environment, with lasting effects. This effect may contribute to reinforcement of early smoking behavior and development of nicotine dependence.

A randomized, double-blind, placebo-controlled trial of long-acting risperidone in cocaine-dependent men.

OBJECTIVE: There is no approved pharmaco-therapy for cocaine dependence. Risperidone is an atypical antipsychotic drug with combined dopamine-2/serotonin-2 (D(2)/5-HT(2)) antagonist activity that has been effective in reducing cocaine use in some animal studies. We tested the efficacy of a long-acting, injectable preparation of risperidone on cocaine use in active cocaine users. METHOD: Thirty-one cocaine-dependent men who met DSM-IV diagnostic criteria for current cocaine dependence entered a 12-week, randomized, double-blind, placebo-controlled trial of intramuscular risperidone, 25 mg every other week. The primary outcome measure was cocaine use as measured by urinary concentration of cocaine metabolites. Secondary outcomes were self-report of cocaine use and craving, depressive symptoms as measured by the Hamilton Rating Scale for Depression (HAM-D), and adverse events. Participants were recruited during a 12-month period from October 2005 to September 2006. RESULTS: Both groups reduced their cocaine use during the study. There were no between-group differences in the primary measure of cocaine use (urinary metabolites [F = 0.7, p = .41]) or on craving measures. Those assigned to risperi-done reported significantly worsened depressive symptoms (mean +/- SD HAM-D change scores: +7.4 +/- 8.8 vs. -2.3 +/- 5.8, respectively, F = 7.5, p = .018) and gained significantly more weight (mean weight change: +6.3 +/- 9.4 lb vs. -4.0 +/- 8.9 lb, respectively, F = 4.65, p = .044) than those assigned to placebo. CONCLUSION: Treatment with long-acting injectable risperidone in active cocaine users was not associated with reduction in cocaine use or craving and was associated with worsening of depressive symptoms and weight gain. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00385801.

Predictors of early abstinence in smokers with schizophrenia.

BACKGROUND: In patients with schizophrenia, the smoking cessation rate is low and the burden of smoking-related morbidity and mortality is high. Identification of factors associated with abstinence may allow clinicians to optimize treatment prior to a smoking cessation attempt. METHOD: To identify factors associated with successful smoking cessation in patients with a DSM-IV diagnosis of schizophrenia, we analyzed baseline data from 114 stable outpatient smokers with schizophrenia who participated in 1 of 2 smoking cessation trials. The outcome of interest was 4 weeks' continuous abstinence at the end of a 12-week nicotine dependence treatment intervention. Baseline factors associated with abstinence were identified with univariate methods and entered into a manual, forward-selection multivariable regression model to identify independent predictors of abstinence. The study was conducted from March 1999 to February 2004. RESULTS: Fourteen of 114 participants (12%) had biochemically verified 4 weeks' continuous abstinence at week 12. We included 10 noncorrelated variables with a univariate association with abstinence in a multivariable model, controlling for pharmacotherapy, age, and gender. Age at initiation of smoking and baseline variability in attentiveness, as measured by Continuous Performance Test-AX (CPT-AX) hit reaction time standard error, were independently associated with abstinence. For every year increase in age at initiation of smoking, the OR for abstinence was 1.36 (95% CI = 1.01 to 1.83), p = .048. For every millisecond decrease in the variability of the reaction time of CPT-AX, the OR for achieving abstinence was 1.55 (95% CI = 1.07 to 2.24), p = .021. CONCLUSION: Later initiation of smoking was associated with increased and baseline attentional impairment with reduced odds of abstinence. Additional research to further our understanding of the relationship between attentional impairment and cigarette smoking in schizophrenia may lead to improved nicotine dependence treatments for this group.

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.

A double-blind, placebo-controlled trial of adjunctive donepezil in treatment-resistant mania.

INTRODUCTION: Because there is a high rate of partial response to standard thymoleptic medication, novel augmentation strategies for treatment-resistant bipolar disorder are needed. In an open trial, donepezil augmentation was associated with improvement in manic symptoms in 9 of 11 subjects. METHOD: We conducted a 6-week, double-blind, placebo-controlled trial of donepezil for treatment-resistant bipolar mania. Eligible subjects had a Young Mania Rating Scale (YMRS) score of at least 15 despite two or more weeks of proven therapeutic levels of lithium or valproate. Subjects who completed the trial were eligible for an 8-week open trial of donepezil. Subjects were started on donepezil 5 mg/day and were eligible for dose increase to 10 mg/day after 4 weeks. RESULTS: Twelve subjects were enrolled. Eleven subjects received at least 1 week of study medication and were included in the analysis. No subjects in the donepezil group (0/6) and 60% (3/5) in the placebo group met response criteria of >30% reduction in YMRS score (Fisher's Exact p = 0.061). YMRS scores were higher at trial endpoint in the donepezil group 20.17 (3.66) compared with the placebo group [11.20 (4.60), Z = -2.476, p = 0.01]. There were no differences at trial endpoint in Hamilton Rating Scale for Depression (HAM-D) or Brief Psychiatric Rating Scale (BPRS) scores in either the intent-to-treat or the completer analyses. CONCLUSIONS: Donepezil does not appear to be an effective adjunctive treatment for refractory manic symptoms. The strength of the conclusion of this trial is limited by the possibility of a false-negative result due to the small sample.

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.

Building primary care practitioners' attitudes and confidence in mental health skills in a post-conflict society: a Cambodian example.

Our program attempted to integrate community mental health in primary care settings in Cambodia and to evaluate the effects of training on local providers. The training program underwent an extensive evaluation to determine its impact on the mental health knowledge, confidence in performing medical and psychiatric procedures, skills and attitudes of its trainees. One hundred four Cambodian primary care practitioners (PCPs) were trained in a primary care setting in Siem Reap, Cambodia, over a 2-year period. There was a significant improvement in PCPs' confidence in all clusters of medical and psychiatric procedures (counseling, medical evaluation, prescribing medications, psychiatric diagnosis, assessing risk for violence, traditional treatments, and treating trauma victims) comparing baseline to posttraining and baseline to 2-year follow-up (p < 0.05). Only confidence in prescribing psychotropic medications improved from posttraining to 2-year follow-up. This study supports the feasibility of training PCPs in a culturally effective manner in a postconflict society.

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

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.