Substance use disorder is common in patients with schizophrenia and dramatically worsens their outcome. The typical antipsychotic medications, introduced over 50 years ago, are effective for the treatment of psychosis but may have only limited efficacy in patients with these co-occurring disorders because patients continue to use substances while taking them. In preliminary studies, however, several of the atypical antipsychotic medications have shown promise for reducing alcohol and drug use in patients with schizophrenia. A neurobiologic formulation is discussed, suggesting that the use of substances in patients with schizophrenia may be based on a dysfunction within the dopamine-mediated brain reward circuitry, and that clozapine in particular, may potentially ameliorate this dysfunction and lessen the desire for substance use. Medications for the treatment of alcohol use disorders, such as disulfiram, naltrexone and acamprosate, as well as other adjunctive medications, may also be useful. Further studies are required to establish a solid evidence base of best practices for the use of medications in these patients.

Objective: Although supported employment increases job acquisition for people with serious mental illness, data on participants' job tenure have been variable. This study evaluated the effects of a standardized work skills training program (the Workplace Fundamentals Module [WPFM]) on job tenure and other work outcomes among individuals receiving individual placement and support (IPS). The effects of two atypical antipsychotic medications on side effects were also tested. The primary hypothesis tested was that participants in IPS plus WPFM would have increased job tenure compared with those enrolled in IPS only, and the secondary hypothesis was that different antipsychotic medications would yield unique side effects.Methods: A 232 randomized controlled trial compared work outcomes, including job tenure, of participants receiving IPS with or without WPFM for up to two years after obtaining a job. Participants were also randomly assigned to olanzapine or risperidone. Measures of work outcomes, clinical status, and medication side effects were collected.Results: Among 107 participants, 63% obtained at least one job. WPFM did not increase job tenure (51.53 and 41.37 total weeks worked for IPS only and IPS plus WPFM, respectively) or affect other work outcomes. Participants on olanzapine experienced increased body mass index, whereas those on risperidone lost weight, but medications did not differentially affect clinical or job outcomes.Conclusions: Clinic-based skills training did not improve work outcomes accruing from IPS. Risperidone, compared with olanzapine, may reduce body mass but has no differential effect on other work or clinical outcomes.

ClinicalTrials.gov identifier: NCT00130923.

OBJECTIVE Cannabis use disorder is the most common co-occurring drug use disorder in people with schizophrenia and is associated with poor outcomes. We launched a randomized controlled trial to assess the impact of clozapine compared with treatment as usual on cannabis use in patients with schizophrenia and co-occurring cannabis use disorder. METHODS Thirty-one patients with schizophrenia and co-occurring cannabis use disorder were randomly assigned to switch to clozapine or to stay on their current antipsychotic and were then followed weekly for 12 weeks. Blinded raters assessed participants weekly with the Timeline Follow-back for substance use and the expanded Brief Psychiatric Rating Scale for symptoms. Longitudinal random effects models were used to investigate the time-varying differences in cannabis use and other outcomes between the treatment as usual and clozapine groups. RESULTS The two groups differed in average intensity of cannabis use by approximately 4.5 joints/week, with lesser use in the clozapine group (t = −1.77; df = 28.5; p=.086; effect size ~ 0.6). Symptoms and functioning were not different between the two groups. CONCLUSIONS Clozapine may reduce cannabis use among patients with schizophrenia and co-occurring cannabis use disorder. Further controlled trials are warranted.

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Olanzapine is effective in managing markedly to severely ill patients with psychotic disorders in a community mental health center. Simultaneous treatment with olanzapine, case management, and psychosocial rehabilitation leads to enhanced functional improvement among nonrelapsing patients.

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