Abstract

To investigate the associations between psychotropic medication dosage and mortality in patients with bipolar disorder. A nationwide cohort of individuals aged ≥15 years who had received a diagnosis of bipolar disorder in 2010 was identified from the Taiwanese national health-care database linked with the mortality registry and followed up for 5 years. The mean defined daily dose (DDD) of mood stabilizers, antipsychotics, antidepressants, and sedative-hypnotics was estimated, and survival analyses were conducted to assess the effects of degree of exposure to psychotropic medications on mortality. A total of 49,298 individuals (29,048 female individuals, 58.92%) with bipolar disorder were included. Compared with individuals without exposure to mood stabilizers, those prescribed mood stabilizers had a decreased overall mortality risk, regardless of exposure dosage. By contrast, compared with a reference group with no exposure to antipsychotics, individuals using antipsychotics had dose-dependent, increased mortality in both overall causes of deaths and deaths due to cardiovascular diseases, with hazard ratios of 1.13 (95% CI: 1.21-1.42) in the low-dose (<0.5 DDD) group, 1.69 (1.51-1.90) in the moderate-dose (0.5-1.5 DDD) group, and 2.08 (1.69-2.57) in the high-dose (>1.5 DDD) group for overall mortality. In sum, mood stabilizers were associated with decreased overall mortality in individuals with bipolar disorder, regardless of the dosage. However, the use of antipsychotics appeared to be associated with a dose-dependent increased mortality risk. Owing to study limitations, precise information on prior use of psychotropic medications, and patient's adherence to medication are not available. Potential adverse effects and benefits should be carefully considered when prescribing psychotropic medications for long-term use in patients with bipolar disorder.

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