T. S. Stroup,1 T. Gerhard,2 C. Huang,2 S. Crystal,2 M. Olfson1; 1Columbia University, New York, NY, 2Rutgers University, New Brunswick, NJ

BACKGROUND: 30% of patients with schizophrenia receive little benefit from standard antipsychotic medications and are considered to have treatment resistance, which is associated with marked disability, repeated hospitalizations, and high health care costs. In clinical trials, clozapine is efficacious for treatment-resistant schizophrenia, but questions remain about its effectiveness in clinical practice.
METHODS: Using national US Medicaid data from 2001-2009, we examined treatment outcomes of a retrospective cohort of adults with evidence of treatment-resistant schizophrenia that initiated clozapine (n=4,932), and a corresponding 1:1 propensity score-matched cohort that initiated a standard antipsychotic (n=4,932). Primary outcome was time to hospitalization for a mental health reason. Secondary outcomes included time to index treatment discontinuation, time to additional antipsychotic use, incidence of serious medical conditions, and death. Data were analyzed using Cox proportional hazards models.
RESULTS: Clozapine initiation was associated with increased time to hospitalization (HR 0.72; 95% CI, 0.65-0.80), time to index treatment discontinuation (HR 0.75; 0.70-0.80), and time to additional antipsychotic use (0.82; 0.77-0.88), but not with lower mortality (HR 1.39; 0.72-3.30). Clozapine was associated with significantly increased risk of diabetes mellitus (HR 2.09; 1.37-3.19) and intestinal obstruction (2.78; 1.30-5.95).
CONCLUSION: In adults with schizophrenia with evidence of treatment resistance, initiating clozapine compared to a standard antipsychotic was associated with greater effectiveness on several important outcomes. Contrary to prior observational studies, there was no evidence that clozapine was associated with decreased mortality.