4.2 Clinical implications
Serotonin syndrome can occur with the use of a single serotonergic drug – in therapeutic doses or in overdose – but is seen most frequently and with a greater degree of toxicity when combining several serotonergic drugs. The most severe cases described in the literature often involve an monoamine oxidase inhibitor (MAOI) in combination with another serotonergic drug, typically an SSRI4,8,11,21. Concomitant administration of an SSRI and tramadol is the most frequent cause of serotonin syndrome4,22.
Individuals exhibit varying sensitivity to serotonergic influence. Whether this is due to individual pharmacokinetic conditions (e.g. reduced drug metabolism) or individual pharmacodynamic circumstances (e.g. serotonin receptor polymorphism) is not known 8. Although a critical level of serotonin appears to be necessary for the development of serotonin syndrome, patients can present with the syndrome at varying drug dosages and combinations, indicating considerable individual variability in that critical value4,23
While it is not contraindicated to combine drugs with serotonergic effects, clinical caution should be exercised8. The key to preventing – and managing – serotonin syndrome is recognizing the syndrome and paying appropriate attention to the prescription of serotonergic drugs as well as an understanding of the clinical symptoms and diagnostic criteria.