A placebo controlled trial of bupropion for smoking cessation in schizophrenia

Abstract

Background: Schizophrenic patients have high rates of cigarette smoking compared with the general population. We compared sustained-release (SR) bupropion with placebo for smoking cessation in patients with schizophrenic disorders. We also examined how antipsychotic class predicts smoking cessation outcomes with bupropion.

Methods: Thirty-two subjects meeting DSM-IV criteria for schizophrenia or schizoaffective disorder and nicotine dependence were randomized to bupropion SR (BUP, 300 mg/day) or placebo (PLA). Outcomes included treatment retention, smoking abstinence rates, expired breath carbon monoxide (CO) levels, psychotic symptoms, and medication side effects.

Results: Bupropion significantly increased trial endpoint 7-day point prevalence smoking abstinence rates compared with placebo [BUP, 8/16 (50.0%), PLA, 2/16 (12.5%); χ² = 5.24, df = 1, p < .05], and reduced CO levels during the trial [Medication × Time interaction; Z = 3.09, p < .01]. Positive schizophrenia symptoms were not altered by BUP, but negative symptoms were significantly reduced. Atypical antipsychotic drug treatment enhanced smoking cessation responses to BUP. Major side effects were dry mouth, gastrointestinal symptoms, headache, and insomnia.

Conclusions: Our results suggest that 1) BUP enhances smoking abstinence rates compared with PLA in nicotine-dependent schizophrenic smokers; 2) BUP is well-tolerated and safe for use in these patients; and 3) atypical antipsychotics may enhance smoking cessation outcomes with BUP.

Introduction

Schizophrenic patients have high rates of cigarette smoking (58–88%) compared with the general population (∼25%) (George et al 2000a) and are often nicotine-dependent smokers who have great difficulty with smoking cessation Addington 1998, Addington et al 1998, George et al 2000a, Ziedonis and George 1997b. Low intrinsic motivation to quit smoking, which may be related to negative and affective symptoms characteristic of schizophrenic illness, has been proposed as a reason for their difficulties with smoking cessation Addington et al 1997, George et al 2000a, Ziedonis and George 1997b. Consequently, schizophrenic patients are often in the earlier stages for motivation to quit smoking as assessed by the “Stages of Change” model Addington et al 1997, Prochaska and DiClemente 1983. Because patients with schizophrenia are at high risk for developing medical morbidity and mortality related to chronic tobacco use Allebeck 1989, Lichtermann et al 2001, efforts to assist them in quitting smoking are of considerable importance; however, the few studies of smoking cessation in schizophrenic patients have reported lower trial end point and 6-month follow-up smoking abstinence rates Addington et al 1998, George et al 2000a, Ziedonis and Trudeau 1997a compared with studies in nonpsychiatric smokers (Hughes et al 1999), indicating a need to develop better treatments for smoking in this population.

There are a number of potential pharmacologic interventions that could improve smoking cessation outcomes in schizophrenic patients. Three preliminary studies with the atypical antipsychotic agent clozapine suggest that this agent may reduce smoking in schizophrenic patients George et al 1995, McEvoy et al 1995a, McEvoy et al 1999, particularly in heavier smokers (George et al 1995). In contrast, the typical antipsychotic agent haloperidol may increase cigarette smoking (McEvoy et al 1995b). Most recently, we have shown that atypical antipsychotic agents may enhance smoking abstinence rates in combination with nicotine patch (George et al 2000a). The antidepressant agent bupropion hydrochloride, as the sustained-release (SR) formulation (Zyban), has been shown to be effective for the treatment of nicotine dependence in nonpsychiatric smokers Hurt et al 1997, Jorenby et al 1999 and received FDA approval for this indication in 1997. There has been a case report that bupropion SR may assist smoking cessation efforts in schizophrenic patients (Evins and Tisdale 1999), and preliminary studies have suggested the efficacy of bupropion SR in reducing cigarette smoking by schizophrenic patients Evins et al 2001, Weiner et al 2001. It is well appreciated that combining pharmacologic with behavioral treatments enhances outcomes in addictive disorders (Carroll 1997), and preliminary work from our group George et al 2000a, Ziedonis and George 1997b and others Addington 1998, Addington et al 1998 has suggested that combining pharmacotherapies with schizophrenia psychosocial interventions (e.g., psychoeducation, social skills training) and smoking cessation behavioral interventions (e.g., motivational enhancement therapy, relapse-prevention therapy) may improve treatment outcomes and acceptability.

In this preliminary study, our primary goal was to evaluate the safety and efficacy of SR bupropion in comparison with placebo for smoking cessation in nicotine-dependent schizophrenic and schizoaffective cigarette smokers who were motivated to quit smoking. The secondary goal of this study was to examine the effects of antipsychotic treatment class (atypical vs. typical antipsychotic agents) on smoking cessation responses to bupropion in schizophrenic patients.