Geographic and clinical variation in clozapine use in the United States

Psychiatr Serv. 2014 Feb 1;65(2):186-92. doi: 10.1176/


Objective: Antipsychotic medications are largely ineffective for approximately 30% of patients with schizophrenia that is considered "treatment resistant." Clozapine is the only antipsychotic approved for treatment-resistant schizophrenia, but it is rarely used. This nationwide study examined predictors of clozapine use to help identify ways to optimize its use.

Methods: A retrospective study using U.S. Medicaid claims data from 45 states was conducted among 326,119 individuals with a schizophrenia spectrum disorder (ICD-9-CM code 295.X) who initiated one or more antipsychotic treatment episodes between January 2002 and December 2005. Multivariable logistic regression models were used to calculate odds ratios of baseline patient and county factors associated with clozapine initiation.

Results: Among 629,809 unique antipsychotic treatment episodes, 79,934 showed service use patterns consistent with treatment resistance. Clozapine accounted for 2.5% of starts of antipsychotic medication among patients in the overall sample and for 5.5% of starts among patients with treatment resistance. Clozapine initiation was significantly associated with male sex, younger age, white race, more frequent outpatient service use for schizophrenia, and greater prior-year hospital use for mental health. Treatment resistance and living in a county with historically high rates of clozapine use were among the strongest predictors of clozapine use.

Conclusions: The clozapine initiation rate was low compared with the expected proportion of patients who warrant a clozapine trial and was strongly affected by local treatment practices. Efforts to address irregular access to clozapine are needed to improve recovery opportunities for people with schizophrenia in the United States.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / therapeutic use*
  • Drug Prescriptions / statistics & numerical data*
  • Drug Utilization / statistics & numerical data
  • Female
  • Humans
  • Insurance Claim Review / statistics & numerical data*
  • Male
  • Medicaid / statistics & numerical data
  • Middle Aged
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Retrospective Studies
  • Schizophrenia / drug therapy*
  • Schizophrenia / epidemiology
  • United States / epidemiology
  • Young Adult


  • Antipsychotic Agents
  • Clozapine