Clozapine use in patients with schizophrenia and a comorbid substance use disorder: A systematic review

Lifetime prevalence of substance use disorders (SUD) in patients with schizophrenia is nearly 50%. Nicotine, alcohol, and cannabis are the substances most frequently used, with a high percentage of poly-substance users. There are few available data about pharmacological approaches in this population. Amongst antipsychotics, clozapine shows positive evidence in the literature. The aim of the present article is to provide systematic review on the efficacy of clozapine in SUD improvement in schizophrenic patients. PRISMA recommendations were followed (PROSPERO id: CRD42017059299). Five studies for nicotine use and nine studies for SUD (other than nicotine) were analyzed. Regarding nicotine use, results from randomized controlled trials (RCT) have found a decrease in nicotine use after 12 weeks of 200-600 mg/day clozapine, as compared with lower doses. In SUD improvement (other than nicotine), RCT have shown superiority of clozapine when compared with risperidone, in short-term studies (from 4 to 12 weeks) performed in cannabis users. In long-term studies (1 year), clozapine was equal to ziprasidone in reducing cannabis use and equal to treatment as usual in reducing alcohol use. We conclude that positive results on nicotine use are scarce and derived from studies with a low degree of evidence. Evidence of clozapine on SUD (other than nicotine) is stronger, especially when clozapine is compared with first generation antipsychotics in poly-substance users. When compared with second generation antipsychotics, clozapine was superior to risperidone but equal to olanzapine or ziprasidone in poly-substance and cannabis users.