Cardiovascular disease and schizophrenia: do we know enough?

I welcomed the special article by Bailey et al. ¹ I share the authors’ concern over the ‘scandal of premature mortality’ and note their recommendation to urgently review antipsychotic medication when certain adverse effects are experienced (rapid early weight gain or cardiometabolic blood disturbance). The authors do not implicate any particular antipsychotics, but guidelines suggest that clozapine and olanzapine are the most likely antipsychotics to be associated with these side-effects. ² Neither do the authors suggest what the outcome of such a review might be, although I deduce it is implicit in the recommendation that reducing the dose or switching antipsychotic would be likely possible outcomes. I do, however, have one concern with this suggestion which relates to the risk-benefit balance of antipsychotics.

Tiihonen et al ³ present data from a large study which examined the effects of antipsychotics on all-cause mortality, suicide and deaths from ischaemic heart disease; one strength of this study is the examination of all-cause mortality. The researchers found that in people with schizophrenia antipsychotic use is associated with a reduced risk of death (by about a third) when compared with no antipsychotic treatment (hazard ratio 0.68, 95% confidence interval 0.65-0.71); clozapine was associated with a substantially lower risk of all-cause mortality as well as suicide. No pronounced differences between antipsychotics (including clozapine and olanzapine) were noted for mortality from ischaemic heart disease.

Thus, if a patient is switched from clozapine to an alternative antipsychotic, their risk of death may in fact be increased rather than reduced. Further, switching antipsychotics (even olanzapine) does not appear to be associated with a reduction in risk of all-cause mortality or even death from ischaemic heart disease. Given that switching antipsychotic medication is associated with harm, for example by increasing risk of relapse, ⁴ this leads me to question the wisdom of Bailey et al's recommendation to urgently review the antipsychotic prescription in the circumstances they describe.

There may be other reasons for switching antipsychotics but Tiihonen et al's findings suggest that reducing the ‘scandal of premature mortality’ is not one of them. This raises a dilemma for practising clinicians as to how to proceed in these circumstances.