Update your Knowledge with MKSAP 18 Q&A: Answer and Critique


D: Serotonin syndrome

Educational Objective

Diagnose serotonin syndrome.


The most likely diagnosis is serotonin syndrome. The features of hyperthermia, tremor, hyperreflexia, ocular clonus (slow, continuous, horizontal eye movements), other clonus (spontaneous or induced), and anxiety are classic features of this syndrome. Hyperreflexia and clonus help distinguish serotonin syndrome from other hyperthermic syndromes and toxic ingestions. This patient's history supports the diagnosis, which usually occurs after coingestion of several serotonergic medications—for example, fluoxetine and methylenedioxymethamphetamine (“ecstasy”). Treatment is mainly supportive, using benzodiazepines as needed to keep the patient calm and to control blood pressure and heart rate. Physical restraint can lead to agitated exertion and worsen hyperthermia. Autonomic instability is common, so close monitoring is recommended. Only in very severe cases of agitation or hyperthermia do patients need to be deeply sedated, intubated, paralyzed, and sometimes treated with cyproheptadine.

Anticholinergic toxicity is unlikely in this patient because he has no signs of mydriasis, dry mucous membranes, or urinary and bowel retention. He does exhibit hyperthermia and agitation, but has clonus and hyperreflexia, which are not associated with anticholinergic toxicity.

Malignant hyperthermia would be very unlikely without a history of inhaled anesthesia agents or neuromuscular blockade. Clinical features of malignant hyperthermia usually include higher fever, muscle rigidity, and, occasionally, hemorrhage but not hyperreflexia or clonus.

Neuroleptic malignant syndrome would be very unlikely without a history of neuroleptic medications, such as haloperidol. It usually develops subacutely during days or weeks, whereas serotonin syndrome typically develops within hours. Rigidity with hyporeflexia is more common, rather than hyperreflexia and myoclonus in serotonin syndrome. Hyperthermia, altered mental status, and rigidity are features of both syndromes. Neuroleptic malignant syndrome usually takes many days to resolve, whereas serotonin syndrome usually resolves within 24 hours.

Key Point

Classic features of serotonin syndrome include hyperthermia, tremor, hyperreflexia and clonus; treatment is mainly supportive, using benzodiazepines as needed to keep the patient calm and to control blood pressure and heart rate.


Dobry Y, Rice T, Sher L. Ecstasy use and serotonin syndrome: a neglected danger to adolescents and young adults prescribed selective serotonin reuptake inhibitors. Int J Adolesc Med Health. 2013;25:193-9. [PMID: 24006318] doi:10.1515/ijamh-2013-0052

Back to the November 2020 issue of ACP Global