Comparative effectiveness of clozapine and standard antipsychotic treatment in adults with schizophrenia

T. Scott Stroup, Tobias Gerhard, Stephen Crystal, Cecilia Huang, Mark Olfson

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


Objective: The authors compared the effectiveness of initiating treatment with either clozapine or a standard antipsychotic among adults with evidence of treatment-resistant schizophrenia in routine clinical practice. Method: U.S. national Medicaid data from 2001 to 2009 were used to examine treatment out comes in a cohort of patients with schizophrenia and evidence of treatment resistance that initiated clozapine (N=3,123) and in a propensity score-matched cohort that initiated a standard antipsychotic (N=3,123). Interventions were new initiation of clozapine or a standard antipsychotic medication, defined as no exposure to the new medication in the prior 365 days. The primary outcome was hospital admission for a mental disorder. Secondary outcomes included discontinuation of the index antipsychotic, use of an additional antipsychotic, incidence of serious medical conditions, and mortality. Results: Initiation of clozapine was associated with a significantly decreased rate of psychiatric hospital admission (hazard ratio=0.78, 95% CI=0.69-0.88), index antipsychotic discontinuation (hazard ratio=0.60, 95% CI=0.55-0.65), and use of an additional antipsychotic (hazard ratio=0.76,95%CI=0.70-0.82). Clozapine was associated with significantly increased incidence of diabetes mellitus (2.8% for clozapine vs. 1.4% for standard antipsychotic; hazard ratio=1.63, 95% CI=0.98-2.70), hyperlipidemia (12.9% for clozapine vs. 8.5% for standard antipsychotic; hazard ratio=1.40, 95%CI=1.09-1.78), and intestinal obstruction (0.9% for clozapine vs. 0.3% for standard antipsychotic; hazard ratio=2.50, 95% CI=0.97-6.44). Conclusions: In adults with schizophrenia and evidence of treatment resistance, initiating clozapine compared with initiating a standard antipsychotic was associated with greater effectiveness on several important outcomes. Increasing the judicious use of clozapine is warranted together with vigilance to prevent and detect serious medical adverse effects.

Original languageEnglish (US)
Pages (from-to)166-173
Number of pages8
JournalAmerican Journal of Psychiatry
Issue number2
StatePublished - Feb 1 2016

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health


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