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Online ISSN: 1099-176X    Print ISSN: 1091-4358
The Journal of Mental Health Policy and Economics
Volume 7, Issue 2, 2004. Pages: 77-85

Published Online: 30 May 2004

Copyright © 2004 ICMPE.


 

Should Clozapine Continue to be Restricted to Third-Line Status for Schizophrenia?: A Decision-Analytic Model

Philip S. Wang,1* David A. Ganz,2 Joshua S. Benner,3 Robert J. Glynn,4 Jerry Avorn5

1MD, DrPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
2MD, MPH, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
3PharmD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
4PhD, ScD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
5MD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

* Correspondence to: Philip Wang, M.D., Dr.P.H., Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030 Boston, MA 02120, USA
Tel.: +1-617-278 0930
Fax: +1-617-232 8602
E-mail: pwang@rics.bwh.harvard.edu

Source of Funding: Financial support for this study was provided entirely by a Research Career Award from the National Institute of Mental Health (K01-MH0165 to Wang). No pharmaceutical company was involved in any way in the initiation, conduct, or support of this research.

Abstract

Clozapine is currently restricted to patients who have failed at least two trials of other antipsychotic medications. We performed a cost-effectiveness analysis of allowing clozapine to be a first-line treatment versus the current policy of restricting clozapine to third-line status. The target population was patients with schizophrenia in an acute psychotic episode, with a lifetime time horizon and societal perspective. Using clozapine as a first agent would lead to modest gains in life-expectancy as well as quality-adjusted life expectancy, relative to restricting its use to patients who failed 2 conventional antipsychotics. The cost-effectiveness ratio of using clozapine first vs. using clozapine third would be $24,100 per quality-adjusted life year (QALY). In 1-way and probabilistic sensitivity analyses, these findings were robust to a variety of assumptions. Allowing clozapine to be a first-line agent may lead to small gains in life expectancy at moderate but acceptable costs.

 

Background: Clozapine is currently restricted to patients who have failed at least two trials of other antipsychotic medications because of concerns that its use as a first-line agent would lead to greater mortality, mainly through agranulocytosis.
Aims of the Study: We sought to determine the cost-effectiveness of allowing clozapine to be a first-line treatment versus the current policy of restricting clozapine to third-line status.
Methods: We performed a cost-effectiveness analysis using published data from randomized controlled trials and epidemiologic studies. The target population was patients with schizophrenia in an acute psychotic episode, with a lifetime time horizon and societal perspective. Outcome measures included life expectancy, quality-adjusted life expectancy, costs, and cost-effectiveness ratios.
Results: Using clozapine as a first agent would lead to modest gains in life-expectancy as well as quality-adjusted life expectancy, relative to restricting its use to patients who failed 2 conventional antipsychotics. The cost-effectiveness ratio of using clozapine first vs. using clozapine third would be $24,100 per quality-adjusted life year (QALY). In 1-way and probabilistic sensitivity analyses, these findings were robust to a variety of assumptions.
Discussion: Allowing clozapine to be a first-line agent may lead to small gains in life expectancy at moderate but acceptable costs.
Implications: While these results do not shed light on whether clozapine should be the preferred first-line strategy, they do suggest that clozapine should be added to the armamentarium of possible treatments for treatment-sensitive as well as treatment-resistant schizophrenia.


Received 28 April 2003; accepted 4 April 2004

Copyright 2004 ICMPE