Epidemiology and Economic Burden of Serotonin Syndrome With Concomitant Use of Serotonergic Agents: A Retrospective Study Utilizing Two Large US Claims Databases

Abstract

Objective: Serotonin syndrome (SS) is an adverse drug reaction occurring among patients receiving serotonergic agents (SAs), and although SAs are commonly prescribed, the epidemiology and economic burden of SS with concomitant SA use have not been comprehensively examined. The objective of this study was to investigate the prevalence, incidence, and economic burden of SS with SA use.

Methods: A retrospective cohort study was conducted using Veterans Health Administration (VHA) records (identification period: October 1, 2008-September 30, 2012) and commercially insured patient records (Intercontinental Marketing Services PharMetrics Plus; identification period: January 1, 2010-December 31, 2013). Cohorts were based on drug classification and exposure: single monoamine oxidase inhibitor (MAOI), MAOIs in combination with SAs, single non-MAOI SA, and multiple non-MAOI SAs (2, 3, 4, ≥ 5). Participants were aged ≥ 18 years with continuous health plan enrollment for 12 months prior to the first SA claim. Outcomes were SS events (ICD-9-CM: 333.99), annual incidence and prevalence, related health care utilization and costs, and SS incidence relative risk.

Results: Over 15 million patients were identified and categorized by SA prescription type. SS incidence in both populations decreased: 0.19%-0.07% (VHA) and 0.17%-0.09% (commercially insured). Overall SS prevalence decreased during the study period. Compared to single non-MAOI SA patients, SS incidence relative risk was highest among patients prescribed ≥ 5 non-MAOI SAs. Inpatient stays accounted for 4.35% (VHA) and 0.88% (commercially insured) of all SS events. Of SS-related inpatient stays, median costs were $8,765 (VHA) and $10,792 (commercially insured).

Conclusions: SS incidence and prevalence and SS-related hospitalization risk among patients prescribed SAs were low in both populations. This study provides additional information regarding SS risk associated with SA use.