Background: Antipsychotic medication is the cornerstone of schizophrenia treatment. The impact of long-term exposure to antipsychotics on life-expectancy has recently received some attention, partly because awareness is increasing of the differential mortality of people with schizophrenia and the general population.
Methods: A systematic review of studies assessing the association between antipsychotic exposure and mortality in persons with schizophrenia was undertaken.
Results: In total, 12 studies met the inclusion criteria. Three out of five studies examining antipsychotic dosage and higher mortality showed a significant association for one or more antipsychotics. Two out of four found negative effects of antipsychotic polypharmacy on life-expectancy. Some studies found a lower cardiovascular mortality risk with higher treatment intensity or when comparing current versus past or non-use of antipsychotics. Others established a stable correlation between antipsychotic exposure and an increase in cardiovascular mortality. Evidence for differential effects on mortality in favor of second generation (SGA) compared to first generation antipsychotics was inconsistent. No study of SGA drugs had a sufficient follow-up time. A major confounding factor may be a higher risk factor load for somatic disorders in the most severely mentally ill.
Conclusion: There is some evidence that long-term exposure to antipsychotics increases mortality in schizophrenia. More rigorously designed, prospective studies are urgently needed.