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

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

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antipsychotic Agents / economics
  • Antipsychotic Agents / therapeutic use*
  • Clozapine / economics
  • Clozapine / therapeutic use*
  • Decision Support Systems, Clinical*
  • Humans
  • Markov Chains
  • Outcome Assessment, Health Care
  • Probability
  • Quality-Adjusted Life Years
  • Schizophrenia / drug therapy*
  • United States

Substances

  • Antipsychotic Agents
  • Clozapine