Published: 3 March 2016


Serotonin Syndrome: Short Time to Onset, Even with the First Dose

This article is more than five years old. Some content may no longer be current.

Prescriber Update 37(1): 5-6
March 2016

Key Messages

  • Serotonin syndrome may very rarely occur after only one dose of a serotonergic medicine.
  • Serotonin syndrome may also occur when the dose of a serotonergic medicine is increased, with the addition of another serotonergic medicine, or in overdose.
  • The majority of cases occur within 24 hours of taking the suspect medicine.

A recent report to the Centre for Adverse Reactions Monitoring (CARM) described a patient who experienced serotonin syndrome after taking one dose of the selective serotonin reuptake inhibitor (SSRI), escitalopram. Within 24 hours of taking the SSRI, the patient developed tachycardia, hyperreflexia, restlessness and diaphoresis (profuse sweating), consistent with a diagnosis of serotonin syndrome. This case highlights that symptoms may occur within hours of ingesting only one dose of a serotonergic medicine.

Medicine classes associated with serotonin syndrome include antidepressants (eg, SSRIs, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors and tricyclic antidepressants), opioid analgesics (eg, tramadol, pethidine), central nervous system stimulants (eg, amphetamines, ‘Ecstasy’), herbal products (eg, St John’s wort) and other miscellaneous agents (eg, methylene blue, dextromethorphan, linezolid). Further information on medicines linked to serotonin syndrome can be found in the ‘Advice about Serotonin Syndrome’ Alert Communication on the Medsafe website (

Serotonin syndrome is a clinical diagnosis: the classic triad of clinical features includes neuromuscular excitation, autonomic nervous system dysfunction and altered mental state (Table 1)1-5.  Mild cases may be easily missed, but the diagnosis should be suspected if any of these symptoms or signs are manifest after starting or increasing the dose of a potent serotonergic drug or shortly after a second serotonergic drug is added.

Table 1: Signs and symptoms of serotonin syndrome 1-5
Altered mental state Agitation or restlessness
Autonomic dysfunction (effects on functioning of internal organs) Hypertension
Neuromuscular excitation (effects on nerves that control voluntary muscle movement) Tremor
Clonus (spontaneous, inducible or ocular)

Of the 19 reports of serotonin syndrome received by CARM in which time to onset was known, the majority (14 reports) occurred within one week of starting the suspect agent. In a case-series of 39 cases of serotonin syndrome reported in the literature from 1995 to 2000, approximately 75% presented within 24 hours of treatment initiation, a change in dose or overdose of the serotonergic agent6. Treatment involves stopping the serotonergic medicine and providing supportive care. Symptoms usually resolve within 24 hours with treatment.

Healthcare professionals are encouraged to continue reporting serotonin syndrome type reactions to CARM and to include as much information as possible (

  1. Boyer EW, Shannon M. 2005. The Serotonin Syndrome. New England Journal of Medicine 352:1112-1120
  2. Isbister GK, Buckley, NA, Whyte IM. 2007. Serotonin toxicity: a practical approach to diagnosis and treatment. Medical Journal of Australia 187(6): 361-365.
  3. Ables A, Nagubilli R. 2010. Prevention, Diagnosis, and Management of Serotonin Syndrome. American Family Physician 81: 1139-1142
  4. Buckley NA, Dawson AH, Isbister GK. 2014. Serotonin syndrome. British Medical Journal 348: g1626.
  5. Dunkley EJ, Isbister GK, Sibbritt D, et al. 2003. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. Queensland Journal of Medicine 96: 635-642
  6. Mason PJ, Morris VA, Balcezak TJ. 2000. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 79: 201-209.
Hide menus
Show menus
0 1 2 4 5 6 7 9 [ /