Comparative Risk of Suicide-Related Events Across Antidepressant Classes in Autistic Individuals: A New-User Active Comparator Cohort Study
Year: 2026
Type: preprint
Study design: Observational Study
Abstract: Introduction: Comparative evidence on suicide-related outcomes across antidepressant treatments among autistic individuals is limited. We examined associations between antidepressant treatment class and suicide-related events (SREs) among individuals on the autism spectrum initiating antidepressants. Methods: We conducted a retrospective new-user, active-comparator cohort study using the nationwide Truveta database of electronic health records. Autistic individuals initiating antidepressants after an autism spectrum diagnosis were classified by initial treatment as a selective serotonin reuptake inhibitor (SSRI), atypical antidepressant, serotonin-norepinephrine reuptake inhibitor (SNRI), or tricyclic antidepressant (TCA). Pairwise propensity score overlap weighting was used to balance baseline characteristics, and associations with SREs during as-treated follow-up were estimated using weighted Cox proportional hazards models. Results: Among 42,441 autistic antidepressant initiators, atypical antidepressants (hazard ratio [HR], 0.787; 95% confidence interval [CI], 0.632-0.979) and TCAs (HR, 0.487; 95% CI, 0.263-0.902) were associated with lower observed SRE hazards compared with SSRIs, whereas no clear difference was observed for SNRIs (HR, 0.948; 95% CI, 0.651-1.381). In agent-specific analyses, trazodone was associated with a lower observed SRE hazard compared with SSRIs, whereas no clear differences were observed for bupropion or mirtazapine. Exploratory age-stratified analyses suggested a lower hazard for atypical antidepressants versus SSRIs among individuals younger than 18 years, although evidence of effect modification was not consistent across alternative specifications of age. Discussion: Among autistic individuals initiating antidepressants, observed SRE hazards differed across some antidepressant treatment comparisons. The class-level association for atypical antidepressants was not observed consistently across its individual agents, and age-related differences warrant further investigation. Lay Summary: Autistic people are often treated with antidepressants, but little is known about whether different types of antidepressants are associated with differences in rates of suicide-related events. In this large real-world study, we compared several commonly used antidepressant treatments among autistic individuals and found that some treatment groups had lower observed rates of suicide-related events than others, although these findings should be interpreted cautiously because treatment choice may reflect differences between patients that cannot be fully measured in health records. The findings may help inform future research on the safety of antidepressant treatment in autistic people.
Source: medRxiv
Institution: University of Pittsburgh
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W7223296668