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Serotonin toxicity: Rx

The serotonin syndrome is suspected when a patient is exposed to exogenous serotonergic medications, particularly if exposed to multiple agents. The symptoms include but are not limited to agitation, altered mental status, clonus, diaphoresis, tachycardia, hyperthermia and hypertension. The syndrome varies significantly in its severity, with many minor cases likely going undiagnosed, ranging to very severe illness requiring ICU stay, multiorgan failure, and even death as a result of the syndrome.

The mainstay of treatment for severe serotonin syndrome is cessation of the offending agent(s) and supportive care, as the symptoms will abate with time. Supportive care may include active cooling, mechanical ventilation, sedation, and hemodynamic support as appropriate. The prototypical sedative for severe serotonin syndrome is a benzodiazepine infusion. Propofol and dexmedetomidine have also proven useful. In extreme cases pharmacologic paralysis may be indicated if gas exchange is profoundly impaired or metabolic demand is unable to be adequately controlled. Temperature management consists of both external cooling as well as cooled intravenous fluids.

The most well-studied pharmacologic intervention for serotonin syndrome is cyproheptadine. Cyproheptadine is an antihistamine with antiserotonergic properties. It is only available as an oral formulation, so enteral access is required. Some atypical antipsychotics have also been used due to antiserotonergic effects, such as olanzapine and chlorpromazine. Notably, chlorpromazine may cause hypotension, and is therefore contraindicated in the patient who has progressed to shock as a result of the syndrome. Despite early postulation that it may be beneficial in this hyperthermic state, dantrolene has not been shown to be effective for treatment of the serotonin syndrome, and is not recommended.


  1. Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008 Jul; 54(7): 988–92. Link
  2. Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome . Ann Pharmacother. 2014;48:1651-4. Link