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

ABSTRACT

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.