Background: Long-term cataract risks associated with first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs), and their associations with metabolism-related diseases are not yet elucidated. Methods: Using Taiwan National Health Insurance data, we conducted a propensity score matched population-based cohort study consisting of 10,014 patients with newly diagnosed schizophrenia from 2005 to 2009 and followed them until the end of 2013. A Cox hazard model with metabolism-related diseases as time-dependent covariates was adapted to estimate the hazard ratio (HR) of cataracts between SGAs and FGAs groups. Results: During the 8-year follow-up, patients receiving SGAs were associated with a higher risk of cataract than those receiving FGAs with an adjusted HR of 1.59 (95% confidence interval [CI] = 1.06–2.36). Patients receiving high-metabolic-risk SGAs (clozapine and olanzapine) showed the highest risk of cataracts among SGAs when compared with those receiving FGAs (aHR = 2.57, 95% CI: 1.35–4.88). SGAs demonstrated a stronger contribution in the risk of cataract in patients without diabetes mellitus (DM) and hyperlipidemia than in those developed these diseases. Patients who developed DM or hyperlipidemia after receiving antipsychotics had an approximately 2.5-fold increased cataract risk over those who did not develop these diseases. Conclusions: Regardless of the condition of metabolic-related diseases, SGAs were independently associated with an increased risk of cataract. DM and hyperlipidemia developed after antipsychotics contributed to the risk of cataract risk.
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