SMOKING, SCHIZOPHRENIA, AND ATYPICAL ANTIPSYCHOTICS

The puzzle of why patients with schizophrenia have extremely high prevalence rates (80 percent) for cigarette smoking has intrigued researchers for many years. We have demonstrated that the amount patients smoke increases significantly during pharmacotherapy with the typical antipsychotic haloperidol, but decreases significantly when patients switch from haloperidol to pharmacotherapy with atypical antipsychotic, clozapine. Nicotine corrects certain deficits in sensory gating and cognitive psychomotor performance that are not corrected, or made worse, by haloperidol. Clozapine corrects these deficits, thereby diminishing the usefulness of nicotine to patients. However, clozapine has restricted use because of its potentially fatal side effect, agranulocytosis. We will determine, in 60 newly admitted patients with schizophrenia who smoke, whether pharmacotherapy with the recently FDA approved atypical antipsychotic, olanzapine, is associated with significantly lower scores on measures of smoking than pharmacotherapy with haloperidol, relative to a baseline antipsychotic-free period (Study 1). We will also utilize a 2 x 2 factorial design, involving 80 recovering inpatients with schizophrenia who express a desire to quit or reduce their smoking, to determine whether pharmacotherapy with olanzapine versus haloperidol, and pretreatment with a nicotine/mecamylamine combination versus placebo/placebo combination, are associated with more successful outcomes during smoking cessation/reduction treatment (Study 2).