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Clozapine more effective than standard antipsychotics for treatment-resistant schizophrenia

Initiation of clozapine among individuals with treatment-resistant schizophrenia was associated with lower rates of psychiatric hospital admission, index antipsychotic discontinuation and use of additional antipsychotics compared with initiation of a standard antipsychotic, according to recent study results.

“A minority of patients with treatment-resistant schizophrenia in the United States is treated with clozapine. Treatment patterns suggest that local practice preferences are important in determining whether clozapine is prescribed. Clozapine is often used as a last resort rather than earlier in the course of illness before the onset of chronic disability. When a new treatment strategy is needed, clinicians often choose to switch to another standard (ie, nonclozapine) antipsychotic or to combine medications rather than initiate clozapine,” T. Scott Stroup, MD, MPH, of Columbia University and New York State Psychiatric Institute, New York, and colleagues wrote. “Limited information about the performance of clozapine compared with other treatment strategies in usual practice may contribute to its underuse in routine clinical settings.”

To compare efficacy of initiating treatment with clozapine vs. a standard antipsychotic for treatment-resistant schizophrenia, researchers evaluated U.S. national Medicaid data from 2001 to 2009 for 3,123 individuals who initiated clozapine and 3,123 who initiated a standard antipsychotic.

Initiation of clozapine was associated with a lower rate of psychiatric hospital admission (HR = 0.78; 95% CI, 0.69-0.88), index antipsychotic discontinuation (HR = 0.6; 95% CI, 0.55-0.65) and use of additional antipsychotics (HR = 0.76; 95% CI, 0.7-0.82).

Clozapine was associated with an increased incidence of diabetes (2.8% vs. 1.4%), hyperlipidemia (12.9% vs. 8.5%) and intestinal obstruction (0.9% vs. 0.3%), compared with a standard antipsychotic.

“The results strongly support efforts to increase the judicious use of clozapine. One approach involves greater emphasis during psychiatric training on the effective and safe prescription of clozapine. Other strategies include continuing education forums and the creation of clinics that specialize in clozapine,” Stroup and colleagues wrote. “The rationale for expanding access to clozapine increasingly rests not only on its unique efficacy in clinical trials of patients with treatment-resistant schizophrenia, benefits in reducing suicidal behaviors, and low rate of use, but also on accumulating evidence supporting its unique effectiveness in community practice.” – by Amanda Oldt

Disclosure: Stroup reports an investigator role in a study sponsored by Auspex Pharmaceuticals and participating in CME activities sponsored by Genentech. Please see the full study for a list of all researchers’ relevant financial disclosures.