Antipsychotic treatment and mortality in schizophrenia

It is generally believed that long-term use of antipsychotics increases mortality and, especially, the risk of cardiovascular death. However, there are no solid data to substantiate this view.

We identified all individuals in Sweden with schizophrenia diagnoses before year 2006 (N = 21 492), aged 17-65 years, and persons with first-episode schizophrenia during the follow-up 2006-2010 (N = 1230). Patient information was prospectively collected through nationwide registers. Total and cause-specific mortalities were calculated as a function of cumulative antipsychotic exposure from January 2006 to December 2010.

Compared with age- and gender-matched controls from the general population (N = 214920), the highest overall mortality was observed among patients with no antipsychotic exposure (hazard ratio [HR] = 6.3, 95% CI: 5.5-7.3), ie, 0.0 defined daily dose (DDD)/day, followed by high exposure (>1.5 DDD/day) group (HR = 5.7, 5.2-6.2), low exposure (<0.5 DDD/day) group (HR = 4.1, 3.6-4.6), and moderate exposure (0.5-1.5 DDD/day) group (HR = 4.0, 3.7-4.4). High exposure (HR = 8.5, 7.3-9.8) and no exposure (HR = 7.6, 5.8-9.9) were associated with higher cardiovascular mortality than either low exposure (HR = 4.7, 3.7-6.0) or moderate exposure (HR = 5.6, 4.8-6.6). The highest excess overall mortality was observed among first-episode patients with no antipsychotic use (HR = 9.9, 5.9-16.6).

Among patients with schizophrenia, the cumulative antipsychotic exposure displays a U-shaped curve for overall mortality, revealing the highest risk of death among those patients with no antipsychotic use. These results indicate that both excess overall and cardiovascular mortality in schizophrenia is attributable to other factors than antipsychotic treatment when used in adequate dosages.