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Published Online: 6 November 2015

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

Abstract

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 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.

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.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 166 - 173
PubMed: 26541815

History

Received: 13 March 2015
Accepted: 2 July 2015
Published online: 6 November 2015
Published in print: February 01, 2016

Authors

Details

T. Scott Stroup, M.D., M.P.H.
From the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York; and the Institute for Health, Health Care Policy and Aging Reearch, Rutgers University, New Brunswick, N.J.
Tobias Gerhard, Ph.D.
From the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York; and the Institute for Health, Health Care Policy and Aging Reearch, Rutgers University, New Brunswick, N.J.
Stephen Crystal, Ph.D.
From the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York; and the Institute for Health, Health Care Policy and Aging Reearch, Rutgers University, New Brunswick, N.J.
Cecilia Huang, Ph.D.
From the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York; and the Institute for Health, Health Care Policy and Aging Reearch, Rutgers University, New Brunswick, N.J.
Mark Olfson, M.D., M.P.H.
From the Department of Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York; and the Institute for Health, Health Care Policy and Aging Reearch, Rutgers University, New Brunswick, N.J.

Notes

Address correspondence to Dr. Stroup ([email protected]).

Funding Information

Dr. Stroup serves as an investigator in a study sponsored by Auspex Pharmaceuticals; and he has participated in CME activities sponsored by Genentech. Dr. Gerhard serves on an external safety review committee for a Merck study; he has provided expert consultation to a law firm on behalf of Roche; and he has received compensation from Boehringer for a talk at an internal CER symposium. Dr. Olfson serves as principal investigator on a grant to Columbia University from Sunovion Pharmaceuticals. All other authors report no financial relationships with commercial interests.

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