Talk to the Veterans Crisis Line now
U.S. flag
An official website of the United States government

VA Health Systems Research

Go to the VA ORD website
Go to the QUERI website
Publication Briefs

Use of Clozapine for Veterans with Treatment-Resistant Schizophrenia Could Result in Significant Cost Savings

Clozapine is the only treatment proven effective for treatment-resistant schizophrenia, and is FDA-approved to decrease suicidal behavior associated with schizophrenia. However, clozapine is associated with side effects including significant weight gain, diabetes, and myocarditis, as well as significant adverse drug reactions that require compliance with an FDA-mandated risk mitigation and evaluation strategy program. Only 20% of Veterans with treatment-resistant schizophrenia in the VA receive clozapine, implying that about 80% are receiving less effective treatments. This cost-benefit analysis sought to simulate potential cost savings for VA that would result from increasing the use of clozapine among Veterans with treatment-resistant schizophrenia. Investigators conducted a systematic review of published studies from January 1985 through June 2015 to assess clozapine's effects on treatment response, suicides, adverse drug reaction rates (and associated mortality), as well as the effects on inpatient hospitalization. The pooled results of these studies, in addition to known VA demographics, were used as the basis for the simulation analyses.


  • Modest increases in clozapine use could result in significant cost savings for VA. Among Veterans with treatment-resistant schizophrenia, VA would save $22,444 per Veteran over the first year of treatment, primarily from 18.6 fewer inpatient hospitalization days per patient. Given this finding, if current clozapine use was doubled from 20% of patients with treatment-resistant schizophrenia to 40%, VA would accrue an estimated cost savings of $80 million over the first year. Moreover, full utilization of clozapine would save VA $320 million over the first year.
  • If all Veterans with treatment-resistant schizophrenia initiated clozapine, it would result in an additional 743 serious adverse drug reactions (ADRs) in year one. Doubling clozapine use from the present 20% of patients to 40% would result in an additional 149 serious ADRs.
  • If all Veterans with treatment-resistant schizophrenia initiated clozapine, 19 suicides would be averted, while there would be a total of 18 additional deaths, 3 due to clozapine-related agranulocytosis and 15 due to ileus (blockage of the intestines). If only 20% started clozapine, there would be 3 deaths due to clozapine-related ADRs and 3 fewer suicides.


  • Findings suggest VA should strongly consider initiatives to substantially increase clozapine use among Veterans with treatment-resistant schizophrenia.
  • Deaths from clozapine-related adverse events are more than balanced out by decreased incidence of suicide attempts, with a net result of slightly fewer deaths with increased use of clozapine.


  • Savings in year 1 of clozapine therapy are modest compared to savings in subsequent years, when monitoring costs are greatly reduced but benefits continue to accrue. Therefore, the results of the present analysis, if anything, underestimate the cost savings for the VA healthcare system.
  • Benefits of improved control of schizophrenia, such as improved quality of life for patients, were not considered. Costs and cost savings for the patient were also not considered.

PubMed Logo Gören J, Rose A, Smith E, and Ney J. The Business Case for Expanded Clozapine Utilization. Psychiatric Services. June 15, 2016;ePub ahead of print.

Related Briefs

» next 171 Medication Briefs...

» next 225 Mental Health Briefs...

What are HSR Publication Briefs?

HSR requires notification by HSR-funded investigators about all articles accepted for publication. These journal articles are reviewed by HSR and publication briefs or summaries are written for a select number of articles that are then forwarded to VHA Central Office leadership to keep them informed about important findings or information. Articles to be summarized are selected by HSR based on timeliness of the findings, interest of leadership, or potential impact on the organization. Publication briefs are written for only a small number of HSR published articles. Visit the HSR citations database for a complete listing of HSR articles and presentations.

Questions about the HSR website? Email the Web Team

Any health information on this website is strictly for informational purposes and is not intended as medical advice. It should not be used to diagnose or treat any condition.