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Practice Practice Pointer

Serotonin syndrome

BMJ 2014; 348 doi: (Published 19 February 2014) Cite this as: BMJ 2014;348:g1626

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Re: Serotonin syndrome

It was with much interest that I read the article on Serotonin Syndrome by Nicholas A Buckley et al in the British Medical Journal of 1st March 2014.

Hunter Serotonin Toxicity Criteria(1), includes neuromuscular hyperactivity, autonomic hyperactivity, and altered mental state. Mild symptoms of Serotonin Toxicity can be easily overlooked in a busy General Practice setting when patients present with headache, diarrhoea or mild tremor.

A recent publication in Cephalalgia by Sanjay Prakash et al(2) shows that headache can be a presenting feature for Serotonin Toxicity and it is important that headache should be considered as an initial presenting symptom of Serotonin Toxicity.

There is evidence to show that higher concentrations of serotonin can bind to 5-HT2A receptors and can induce a migraine attack(3-7). Triptans are selective agonists at 5-HT 1B/1D/1F receptors and hence the suggestion that triptans do not cause Serotonin Toxicity. Up regulation of 5-HT2A receptors have been observed in Chronic Daily Headache and in Medication Overuse Headache(8). It is possible that activation of 5HT2A receptors may be the mechanism causing headache in Serotonin Syndrome.

1. Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH and Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM (2003) 96 (9): 635-642.
2. Prakash S, Belani P, Trivedi A. Headache as a presenting feature in patients with serotonin syndrome: A case series. Cephalalgia. March 2014, 34 (3).
3. Sommer C. Serotonin in Pain and Pain Control. Handbook of Behavioral Neuroscience. Volume 21, 2010, Pages 457–471.
4. Turkel SB, Nadala JG, Wincor MZ. Possible serotonin syndrome in association with 5-HT(3) antagonist agents. Psychosomatics. 2001 May-Jun;42(3):258-60.
5. Gollapudy S, Kumar V, Dhamee MS. A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient receiving paroxetine, duloxetine, and bupropion. J Clin Anesth. 2012 May;24(3):251-2. doi: 10.1016/j.jclinane.2011.04.017.
6. Evans RW, Tepper SJ, Shapiro RE, Sun-Edelstein C, Tietjen GE. The FDA alert on serotonin syndrome with use of triptans combined with selective serotonin reuptake inhibitors or selective serotonin-norepinephrine reuptake inhibitors: American Headache Society position paper. Headache. 2010 Jun;50(6):1089-99. doi: 10.1111/j.1526-4610.2010.01691.x.
7. Srikiatkhachorn A, Govitrapong P, Limthavon C. Up-regulation of 5-HT2 serotonin receptor: a possible mechanism of transformed migraine. Headache. 1994 Jan;34(1):8-11.
8. Srikiatkhachorn A, Anthony M. Serotonin receptor adaptation in patients with analgesic-induced headache. Cephalalgia. 1996 Oct;16(6):419-22.

Competing interests: No competing interests

07 March 2014
Anna Alexander
Gossops Green Medical Centre
Gossops Green, Crawley