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Potential drug-drug interaction risks of selective serotonin reuptake inhibitors in outpatients: a retrospective analysis using two screening databases

Year: 2026

Type: article

Abstract: Introduction: Potential drug-drug interactions (pDDIs) involving selective serotonin reuptake inhibitors (SSRIs) pose significant risks in psychiatric care, where polypharmacy often exacerbates pharmacokinetic and pharmacodynamic effects through cytochrome P450 enzyme pathways. This retrospective study aimed to assess the prevalence, characteristics, and risk factors of pDDIs associated with SSRIs in outpatients. Methods: We conducted a retrospective study on outpatients admitted to Beijing Tongren Hospital from January 2023 to December 2024. The patients were ≧18 years old and treated with two or more drugs including at least one SSRI. Micromedex® and Lexi-Interact® were used to identify pDDIs and their severities, and logistic regression was employed to identify demographic predictors such as gender, age, and number of concomitant medications. Results: A total of 3476 prescriptions involving 1186 patients were included in the analysis. A prevalence of 19.68% was observed, with an average of 2.05 pDDIs per affected prescription. 98.83% of interactions detected by Micromedex® were classified as major, whereas among those detected by Lexi-Interact®, 68.76% were classified as moderate and 21.50% as minor. Agreement between the two databases on severity was poor (Cohen's κ = 0.034) when the same drug pairs were rated by both. Common interacting drug classes included antipsychotics (292 instances), other antidepressants (207), blood glucose-lowering agents (207), antithrombotic agents (193), and calcium channel blockers (157). Predominant clinical consequences encompassed QT interval prolongation (569 cases), serotonin syndrome (390), bleeding (229), and hypoglycemia (207), aligning with serotonergic excess and platelet function theories. Female gender, middle age (40-64 years), and polypharmacy were significantly associated with higher pDDI risks. Conclusion: This retrospective study found pDDIs involving SSRIs relatively uncommon among general hospital outpatients, a broader, less-studied population than prior psychiatric or nursing home cohorts, yet still linked to severe outcomes, especially among female, middle-aged patients on polypharmacy. Discrepancies between interaction-severity databases underscored the need for multi-tool assessment. Future prospective, multi-centre studies are needed to inform safer outpatient psychiatric prescribing.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1965339