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

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.