Comparative Effectiveness of Clozapine and Standard Antipsychotic Treatment in Adults With Schizophrenia

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.

U.S. national Medicaid data from 2001 to 2009 were used to examine treatment outcomes 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.

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).

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.