Context: Polypharmacy is widely used in the treatment of schizophrenia, although it is believed to have major adverse effects on the well-being of patients.
Objective: To investigate if the use of benzodiazepines, antidepressants, or multiple concomitant antipsychotics is associated with increased mortality among patients with schizophrenia.
Design: Registry-based case linkage study.
Setting: Academic research.
Patients: We linked national databases of mortality and medication prescriptions among a complete nationwide cohort of 2588 patients hospitalized in Finland for the first time with a diagnosis of schizophrenia between January 1, 2000, and December 31, 2007.
Main outcome measures: Hazard ratios (HRs) were computed for all-cause mortality during the use of antipsychotics, antidepressants, or benzodiazepines in outpatient care, adjusting for the effects of sociodemographic and clinical variables, geographic location, and current and past pharmacological treatments.
Results: Compared with antipsychotic monotherapy, concomitant use of 2 or more antipsychotics was not associated with increased mortality (HR, 0.86; 95% CI, 0.51-1.44). Similarly, antidepressant use was not associated with a higher risk for mortality (HR, 0.57; 95% CI, 0.28-1.16) and was associated with markedly decreased suicide deaths (HR, 0.15; 95% CI, 0.03-0.77). However, benzodiazepine use was associated with a substantial increase in mortality (HR, 1.91; 95% CI, 1.13-3.22), and this was attributable to suicidal deaths (HR, 3.83; 95% CI, 1.45-10.12) and to nonsuicidal deaths (HR, 1.60; 95% CI, 0.86-2.97). In total, 826 of 904 patients (91.4%) who used benzodiazepines had purchased prescriptions that contained more than 28 defined daily doses, violating treatment guidelines.
Conclusions: Benzodiazepine use was associated with a marked increase in mortality among patients with schizophrenia, whereas the use of an antidepressant or several concomitant antipsychotics was not. Antidepressant use was associated with decreased suicide deaths. The literature indicates that long-term use of benzodiazepines among patients with schizophrenia is more prevalent in other countries (eg, the United States) compared with Finland, which suggests that benzodiazepine use may contribute to mortality among this patient population worldwide.