Serotonin Syndrome

Colleen M. Almgren, DVM, PhD, Pet Poison Helpline, Minneapolis, Minnesota
Justine A. Lee, DVM, DACVECC, DABT, VetGirl, Minneapolis, Minnesota


  • Serotonin (5-hydroxytryptamine [5-HT]) is a biogenic amine naturally present in the body and stored primarily in the presynaptic nerve terminals of the CNS, enterochromaffin cells, and platelets.
  • Serotonin functions in neurotransmission, intestinal motility, regulation of vasomotor tone and blood pressure, and platelet aggregation.
    • Systemic levels in the circulation are normally low


  • Serotonin syndrome (SS) is a spectrum of clinical signs caused by the effects of elevated serotonin levels.
  • Ingestion of certain medications—at therapeutic (eg, adverse effect) or toxic doses—can result in SS (see Medications & Supplements That May Cause Serotonin Syndrome, and the handout, Agents Implicated in Serotonin Syndrome).


  • SS can affect multiple body systems to varying degrees, depending on medication and dose ingested (see Table, below).
  • Tryptophan is converted to 5-hydroxy­tryptophan (5-HTP) and then to serotonin.
    • Accidental poisoning from ingestion of holistic supplements containing 5-HTP can result in significant SS.
  • In humans, SS often occurs with coingestion of ≥2 drugs that alter serotonin metabolism via different mechanisms (eg, selective serotonin reuptake inhibitors [SSRIs], monoamine oxidase inhibitors [MAOIs]), although overdose of single agents has also been reported.1-3
  • In veterinary medicine, most SS cases result from accidental ingestion or overdose of 1 drug.
    • Depending on patient size and drug involved, ≥1 pill may be required to initiate clinical signs.


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