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J Ment Health Policy Econ. 2004 Jun;7(2):77-85.

Should clozapine continue to be restricted to third-line status for schizophrenia?: a decision-analytic model.

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  • 1Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, 1620 Tremont Street, Suite 3030 Boston, MA 02120, USA.



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.


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.


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.


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.


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.

[PubMed - indexed for MEDLINE]
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