Mortality and Antidepressants Among Individuals With Autism Spectrum Disorder: A Population‐Based Cohort Study

Individuals with autism spectrum disorder (ASD) often experience premature mortality and co-occurring psychiatric conditions, for which antidepressants are commonly prescribed. However, the long-term safety of antidepressant use in this population remains unclear. Using data from the Taiwan National Health Insurance Research Database, we emulated a target trial to examine the association between antidepressant use and mortality among individuals with ASD aged 6-64 years diagnosed between 2000 and 2016. A three-step approach of cloning, censoring, and inverse probability of censoring weighting was applied to address immortal-time bias. Participants were followed for up to 5 years to assess all-cause, suicide, and accidental-cause mortality. Among 33,939 eligible individuals, 779 initiated antidepressants within a 3-month grace period. Antidepressant use was not associated with all-cause or suicide mortality overall. However, it was significantly associated with reduced accidental-cause mortality at both 2 (HR = 0.15; 95% CI, 0.04-0.53) and 5 years (HR = 0.05; 95% CI, 0.01-0.20). Subgroup analysis revealed increased 2-year all-cause mortality among youths (HR = 4.40; 95% CI, 1.10-17.58) but significantly decreased 5-year accidental mortality in the age groups of 6-15 years (HR = 0.06; 95% CI, 0.01-0.41) and over 24 years (HR = 0.06; 95% CI, 0.01-0.42). Additionally, decreased 5-year suicide mortality was observed in the 16-24 age group (HR = 0.17; 95% CI, 0.05-0.61). While antidepressant use may reduce accidental mortality in individuals with ASD, age-specific risks warrant careful consideration and monitoring, particularly among younger populations.