Comparative Risk of Suicide-Related Events Across Antidepressant Classes in Autistic Individuals: A New-User Active Comparator Cohort Study
- 1University of Pittsburgh
Abstract
IntroductionComparative 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.
MethodsWe 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.
ResultsAmong 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.
DiscussionAmong 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 SummaryAutistic people are often treated with antidepressants, but little is known about whether different types of antidepressants are associated with different effects on reducing the onsets 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.
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BibTeX
@misc{jiang2026comparative,
title = {{Comparative Risk of Suicide-Related Events Across Antidepressant Classes in Autistic Individuals: A New-User Active Comparator Cohort Study}},
author = {C. Jiang and R. Huang and S. Eldeeb and H. Wang and Z. C. Zeng and K. B. Beck and N. D. Ryan and C. Mazefsky and L. Wang},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.21.26366126},
url = {https://www.medrxiv.org/content/10.64898/2026.10.21.26366126v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Comparative Risk of Suicide-Related Events Across Antidepressant Classes in Autistic Individuals: A New-User Active Comparator Cohort Study
AU - C. Jiang
AU - R. Huang
AU - S. Eldeeb
AU - H. Wang
AU - Z. C. Zeng
AU - K. B. Beck
AU - N. D. Ryan
AU - C. Mazefsky
AU - L. Wang
PY - 2026
DA - 2026/10/21
PB - medRxiv
DO - 10.64898/2026.10.21.26366126
UR - https://www.medrxiv.org/content/10.64898/2026.10.21.26366126v1
AB - IntroductionComparative 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. MethodsWe 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. ResultsAmong 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. DiscussionAmong 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 SummaryAutistic people are often treated with antidepressants, but little is known about whether different types of antidepressants are associated with different effects on reducing the onsets 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.
ER -