Time-to-Onset Analysis of Rhabdomyolysis Associated With Selective Serotonin and Serotonin-Noradrenaline Reuptake Inhibitors Using the Japanese Pharmacovigilance Database.

Abstract

Background/aim: In recent years, reports of serious adverse events associated with selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) have increased. This study aimed to evaluate the association between SSRIs/SNRIs and rhabdomyolysis (RM) and its time-to-onset profiles using data from the Japanese Adverse Drug Event Report (JADER) database.

Patients and methods: We extracted data from the JADER database between April 2004 and June 2023. The association between SSRIs/SNRIs and RM was evaluated using the reporting odds ratio adjusted by sex and age group [adjusted reporting odds ratio (aROR)]. A subanalysis was performed after excluding patients taking concomitant statins or fibrates. In addition, the RM expression profile was evaluated by calculating its onset time and Weibull distribution parameters, and outcomes were examined.

Results: RM was associated with the SSRIs escitalopram [aROR=1.86 (1.07-3.23)], fluvoxamine [aROR=2.41 (1.64-3.54)], paroxetine [aROR=2.59 (2.04-3.30)], and sertraline [aROR=1.76 (1.14-2.72)] as well as the SNRI duloxetine [aROR=1.49 (1.00-2.21)]. The exclusion of patients receiving concomitant statins or fibrates did not significantly affect these results. The median time to onset of RM was 11-62 days, and the Weibull distribution parameter showed that the hazard types were early failure for paroxetine and duloxetine and random failure for others.

Conclusion: RM should be monitored in patients treated with SSRIs/SNRIs, particularly in the first few months of administration, and our results may be helpful for the safety management of such patients.