Influence of antipsychotics on mortality in schizophrenia: evidence from observational studies

In the last years, the impact of long-term exposure to antipsychotics on survival has received some attention as the differenzial mortality gap between people with schizophrenia and the general population has worsened in recent decades, and some second generation antipsychotics (SGA) increase the risk for metabolic syndrome. We performed a systematic review of observational studies assessing the association between antipsychotic exposure and mortality in persons with schizophrenia. 12 studies could be included which showed high overall and cardiovascular mortality rates. Four out of seven studies with sufficient information found an association between antipsychotic dosages or between antipsychotic polypharmacy and mortality. The retrospective studies were inconsistent with some showing a lower cardiovascular mortality risk with higher treatment intensity or current versus past or non-use of antipsychotics, and others establishing a stable correlation between antipsychotic exposure and cardiovascular mortality. Some studies showed lower mortality risks with SGA compared to first generation antipsychotics, however, evidence for differenzial effects on mortality were inconsistent. A major confounding factor may be a higher risk factor load for somatic disorders in the most severely mentally ill. There is some evidence that long-term exposure to antipsychotics further increases mortality. The choice of antipsychotics should reflect both mental and and physical health needs.