Serotonin Syndrome in Tapentadol Literature: Systematic Review of Original Research.

The potential association between serotonin syndrome and tapentadol is not well described in the literature. This study aimed to review the literature and identify methodological issues that could lead to inaccurately reported rates of serotonin syndrome associated with tapentadol use. A systematic review of English articles using MEDLINE, Cochrane Controlled Trials Register, and Scopus was performed. Additional studies were identified by cross-referencing article bibliographies. Original research that examined the safety of tapentadol in patients with nonconfounding indications were examined. In total, 22 studies met inclusion criteria. There were 13 randomized clinical trials, 7 open-label trials, and 2 observational studies. All studies either did not mention whether serotonergic medication use was prohibited or disallowed use. Frequently reported adverse events were nausea, diarrhea, constipation, fatigue, vomiting, and somnolence. No studies reported serotonin syndrome development. No included trials differentiated between the development of adverse events in patients taking serotonergic drugs and those who were not. This differentiation is necessary to evaluate the increased risk of adverse events in patients prescribed tapentadol concomitantly with other serotonergic medications. Therefore, the current tapentadol literature has important limitations that prevent the adequate characterization of the potential association between tapentadol and serotonin syndrome.