(072) Association between Mortality and Cumulative Exposure to Antipsychotics, Antidepressants and Benzodiazepines in Patients with Schizophrenia: A Real-World Observational Study
Background: The benefits of antipsychotics in schizophrenia are well established. However, whether the use of antidepressants or benzodiazepines is safe for patients with schizophrenia remains unclear.
Objectives: The aim of this study was to evaluate whether the cumulative dosage of antipsychotics, antidepressants, or benzodiazepines in the treatment of schizophrenia is associated to a different risk of mortality.
Methods: This is a retrospective cohort study of patients living in Quebec (Canada), aged 17-64 years, diagnosed with schizophrenia between 01/01/2002-31/12/2012. Medico-administrative databases were used. Exposure to all drugs was measured using defined daily doses and exposure levels (small, moderate or high dose). All patients were followed for 5 years from 01/01/2013. The measured outcome was all-cause mortality within 5 years. Covariates included sex, age, receiving social welfare, date of the first diagnosis of schizophrenia, substance-use disorders, history of: 1) personality disorder, 2) use of lithium, divalproex, lamotrigine or mood stabilizers, 3) health care utilization with reasons, and comorbidity index. Descriptive statistics and survival analyses were performed. Cox proportional hazards regression models were used (adjusted for age, sex, and covariates that were associated with the outcome in univariate analyses); validity assumptions were verified. Post-hoc sensitivity analyses were also conducted.
Results: A total of 32,240 patients were included in the cohort. Mean age was 46 years old, 39% were female. During the baseline period, 89% were using an antipsychotic, 41%: antidepressant and 50%: benzodiazepine (7%: none). During follow-up, 6% of the cohort died. Compared to non-current use at the time of the event, the risk of mortality was lower for antipsychotic users (adjusted hazard ratio: 0.72 [95% confidence interval: 0.64-0.81]) and antidepressant users (0.90 [0.89-0.99]) but greater for benzodiazepine users (1.20[1.10-1.32]). A dose-response association was not observed among antidepressant users during the 5-year follow-up (small: 1.10[0.97-1.25], moderate: 0.92[0.82-1.04], high: 1.03[0.87-1.21]). However, the risk with benzodiazepine increased proportionally with the dose compared to no exposure (small: 1.44[1.30-1.60], moderate: 1.54[1.36-1.75], high: 1.69[1.29-2.22], and this was confirmed with post-hoc sensitivity analyses (small: 1.44[1.28-1.62], moderate: 1.51[1.31-1.73], high: 1.71[1.33-2.19]).
Conclusions: In this cohort of patients with schizophrenia, antidepressant use was somewhat associated with better 5-year survival, while it was the opposite for the use of any dose of benzodiazepines.
