Serotonin Syndrome
Serotonin syndrome is a potential life-threatening condition resulting from increased serotonin activity in the central nervous system.
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Nantthasorn Zinboonyahgoon and Mohammed Issa Pharmacology
Diagnostic Criteria
Serotonin syndrome involves stimulation of the postsynaptic 5-HT1A and 5-HT2A receptors. It results from any combination of drugs that has the net effect of increasing serotonergic neurotransmission, most commonly serotonergic antidepressants (SSRIs, SNRIs, TCAs, MAOIs). Other drugs may include analgesics (tramadol), antiemetics (metoclopramide, ondansetron), triptans, and drugs of abuse (MDMA, LSD).
Diagnosis is based on clinical findings using the Hunter toxicity criteria. The patient must have taken a serotonergic agent and meets ONE of the following conditions: • • • • •
Spontaneous clonus Inducible clonus PLUS agitation or diaphoresis Ocular clonus PLUS agitation or diaphoresis Tremor PLUS hyperreflexia Hypertonia PLUS hyperpyrexia (>38 C) PLUS ocular clonus or inducible clonus
Clinical Special Considerations Clinical Manifestations Classic serotonin syndrome is described as a triad of mental status changes (agitation, disorientation, delirium), autonomic hyperactivity (tachycardia, hypertension, hyperthermia, diaphoresis), and neuromuscular abnormalities (tremors, myoclonus, hyperreflexia, muscle rigidity). The onset is acute, usually starting within 6–24 h.
N. Zinboonyahgoon, MD (*) Department of Anesthesiology, Siriraj Hospital, Mahidol University, 2 Phranok Road, Siriraj, Bangkoknoi, Bangkok 10700, Thailand e-mail: [email protected] M. Issa, MD Department of Anesthesiology and Psychiatry, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA e-mail: [email protected]
In severe serotonin syndrome, patients can develop hypotension, hyperthermia, rigidity, and rhabdomyolysis, which may be difficult to distinguish from neuroleptic malignant syndrome (NMS). NMS is slower in onset (develops over days to weeks), takes longer to resolve (9 days as compared to less than 24 h for serotonin syndrome), and involves sluggish neuromuscular responses, unlike neuromuscular hyperactivity seen in serotonin syndrome.
Treatment • Discontinue all serotonergic agents. • Supportive care to normalize vital signs. • Sedation with benzodiazepines to control agitation and vital signs. If this fails, consider using serotonin antagonists such as cyproheptadine.
© Springer International Publishing Switzerland 2017 R.J. Yong et al. (eds.), Pain Medicine, DOI 10.1007/978-3-319-43133-8_56
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• For severe cases, patients may need to be admitted to the ICU for hemodynamic control or intubation and paralysis.
Clinical Pearls • Serotonin syndrome involving MAOIs may be more severe and can be lethal. • Serotonin syndrome may result from therapeutic medication use, inadvertent interactions
N. Zinboonyahgoon and M. Issa
between drugs, and/or intentional self-poisoning. • If tramadol is to be prescribed with a serotonergic drug, do not exceed a daily dose of 300 mg.
Suggested Readings Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352:1112–20. Lerner BA. A life-changing case for doctors in training
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