Effect of clozapine on mortality

Duggan et al (2003) elegantly model the effect of clozapine on suicide, and highlight that 53 lives could be saved each year if all patients with treatment-resistant schizophrenia were offered clozapine treatment. The model does not, however, take into account the effect of clozapine on mortality from causes other than suicide. Clozapine is associated with weight gain, diabetes mellitus, and increased mortality from pulmonary embolism and other adverse events in addition to the risk of agranulocytosis (Walker et al, 1997). Fontaine et al (2001) estimated mortality due to clozapine-associated weight gain using data from the Framingham Heart Study. They conclude that the reduction in the suicide rate would be almost entirely offset over 10 years by the increased mortality associated with weight gain of 10 kg. Walker et al (1997) report that mortality from causes other than suicide is increased with clozapine treatment, although overall mortality is lower. To completely model the effect of clozapine on mortality, the effects of the alternatives – active treatment and no treatment – on mortality, including suicide and adverse events related to treatment with other antipsychotics, should be included. These remarks do not detract from the main point that clozapine is still the most effective intervention for treatment-resistant schizophrenia, and mortality is only one outcome to be weighed in the overall risk–benefit analysis.