Background: The aim of this study was to assess the association between various classes of antidepressants and the risk of medication noncompliance as well as suicidal behavior among depressed patients. Methods: A retrospective cohort study was conducted utilizing two nationwide population-based datasets in Taiwan from 2010 to 2016. The outcome measures included the risk of medication noncompliance, attempted suicide, and completed suicide. Cox proportional hazards models with stratification of the propensity score deciles were performed. Results: A total of 447,411 new antidepressant users were identified. Compared to SSRIs, patients who received SARIs [adjusted hazard ratio (aHR) = 1.124, 95% confidence interval (CI) = 1.108–1.142], SNRIs (aHR = 1.049, 95% CI = 1.033–1.065), and other classes of antidepressants (aHR = 1.037, 95% CI = 1.024–1.051) were more likely to exhibit poor medication noncompliance. Patients who received SNRIs had a higher risk of attempted suicide (aHR = 1.294, 95% CI = 1.114–1.513), compared to SSRIs. However, patents in the TCAs group revealed the opposite result (aHR = 0.543, 95% CI = 0.387–0.762). Concerning the risk of completed suicide, this analysis detected no statistical significance across different types of antidepressants. Limitations: Although the universal coverage of Taiwan's national health insurance program tends to minimize the risk of selection and recall bias, it is difficult to rule out medical surveillance bias by using claim data. Conclusions: This study demonstrated that classes of antidepressants exert different degrees of impact on the risk of medication noncompliance and attempted suicide, but not completed suicide, among depressed patients.
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