Clinical Severity and Serotonin Toxicity in Antidepressant Self-Poisoning: Implications for Clinical Risk Assessment

Background: Antidepressant self-poisoning is a common form of intentional self-harm, and comparisons across antidepressant groups are complicated by differences in ingested dose and coexposures. Methods: This retrospective cross-sectional study reviewed emergency department presentations coded with International Classification of Diseases, 10th Revision (ICD-10) X61/X64 between 01 January 2023 and 15 May 2025. Among 15,160 screened records, 168 patients with documented antidepressant ingestion with self-harm/suicidal intent were included. Antidepressant exposures were classified by group and standardized using defined daily dose (DDD). Clinical presentation, serotonin toxicity based on the Hunter Serotonin Toxicity Criteria, management, and short-term outcomes were evaluated. Multivariable logistic regression was used to adjust for log-transformed DDD. Results: The median age was 27.0 years, and 66.7% of patients were female. Selective serotonin reuptake inhibitors (SSRIs) were the most frequently ingested antidepressants (79.8%). Symptomatic presentation occurred in 33.3% of patients and was more frequent in non-SSRI than in SSRI exposures (55.9% vs 27.6%; adjusted OR, 3.40; 95% CI, 1.55-7.43; P = .002). Serotonin toxicity was identified in 7.7% and was also more frequent in non-SSRI exposures (23.5% vs 3.7%; adjusted OR, 8.17; 95% CI, 2.45-27.26; P = .001). Serotonin toxicity was associated with intensive care unit (ICU) admission (53.8% vs 10.3%; P < .001). Conclusion: Non-SSRI antidepressant exposures were associated with greater short-term clinical severity than SSRI exposures. Because non-SSRI subgroups were small and heterogeneous, class-specific findings should be interpreted as exploratory. The early clinical pattern of toxicity may inform short-term risk assessment.