Risks and Benefits of Bupropion Treatment in Schizophrenia: A Systematic Review of the Current Literature

Background: Bupropion inhibits the reuptake of norepinephrine and dopamine, which are involved in the pathogenesis of affective, cognitive, and psychomotor impairment in schizophrenia. Because of reports on bupropion-associated psychoses, it is reluctantly used in schizophrenic patients. Risks and benefits, however, have never been comprehensively reviewed. Objective: The objectives of this study were to evaluate the efficacy of bupropion on depression, negative symptoms, cognition, and smoking habits in schizophrenia and to appraise safety aspects. Methods: MEDLINE OVID/PubMed, scholar. google.com and the Cochrane Database were screened for the keywords ("bupropion"/"wellbutrin"/"elontril"/"zyban") and ("psychosis"/"schizophrenia"/"psychotic disorder"). Study Selection: A total of 13 randomized controlled trials (28 publications), 3 open prospective evaluations, 5 multiple case reports, 22 single case reports, and 6 review articles were incorporated in the final analysis. Data Extraction: Information on patient population, age, diagnosis, bupropion dose and formulation, antipsychotic and concomitant medication, adverse events and treatment outcomes regarding psychosis, affective and negative symptoms, cognition, and smoking habits were collected from the published reports. Results: A total of 30 cases of bupropion-induced psychoses have been published, 17 (57%) of which were associated with the immediate-release drug formulation and 28 (93%) of which occurred without concomitant antipsychotic medication. In comparison, 229 schizophrenic patients on stable antipsychotic regimens were successfully treated with bupropion and experienced marked clinical improvement without developing psychosis. Pharmacokinetic interactions with antipsychotics were rare, whereas electroencephalographic abnormalities occurred frequently. Conclusions: In schizophrenic patients treated with bupropion in addition to antipsychotics, the risk for bupropion-induced psychoses seems negligible. The efficacy of a combined dopamine and norepinephrine agonist in schizophrenia is biologically plausible. Further trials involving bupropion should integrate neurobiological methods and focus on negative symptoms and cognitive deficits in schizophrenia.