Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database.

Background: More information would be required for a better understanding of the actual circumstances of serotonin syndrome (SS) occurrence in routine clinical practice.

Aim: The objective of the study was to analyze characteristics of SS French pharmacovigilance reports, especially involved drugs and nature of drug-drug interactions (DDIs).

Method: We performed a retrospective analysis of SS registered in the French pharmacovigilance database between January 1, 1985 and May 27, 2013. Only cases whose clinical symptoms fulfilled Sternbach, Radomski, or Hunter SS diagnostic criteria were retained for the analysis.

Results: Most of the 125 (84.0%) analyzed cases were associated with a recent change in a serotonergic drug (introduction, increasing the dose or overdose). Antidepressants were the most often involved serotonergic drugs, mostly serotonin reuptake inhibitors (SRIs, 42.1%) and to a lesser extent serotonin-noradrenalin reuptake inhibitors (9.1%, mainly venlafaxine), tricyclic antidepressants (8.6%, mainly clomipramine), and some monoamine oxidase inhibitors (6.2%, mainly moclobemide). Nonpsychotropic medications were also involved, generally opioids (14.8%, mainly tramadol). Most of the cases (59.2%) resulted from pharmacodynamic DDIs, most often involving SRIs + opioids (mostly paroxetine + tramadol). However, SS also occurred with a single serotonergic drug in a significant number of cases (40.8%), most often SRIs (mainly fluoxetine) or venlafaxine at usual doses. Lastly, a major pharmacokinetic DDI could have played a role in 1/5 (20.8%) of cases.

Conclusions: This is the first study about SS based on a large pharmacovigilance database and published in English. Our results reveal not only the frequent involvement of antidepressants and tramadol, the importance of DDIs (both pharmacodynamic and pharmacokinetic), but also the significant risk of SS even with a single serotonergic drug used at normal dose.