Reply to reader's observation: The serotonin syndrome is a clinical diagnosis based on a broad spectrum of certain clinical signs and symptoms after the intake of serotonergic agents. Diagnosis of our case was based on the Hunter Criteria.1 Other sets of diagnostic criteria have been studied for the definition of the serotonin syndrome.2,3 However the Hunter Criteria were more accurate, sensitive (84 per cent vs. 75 per cent), specific (97 per cent vs. 96 per cent) and simpler compared to the original Sternbach Criteria.1,4 Diagnostic Hunter Criteria include spontaneous clonus; inducible clonus and agitation or diaphoresis; ocular clonus and agitation or diaphoresis; tremor and hyperreflexia; hypertonia and temperature above 38*C and ocular or inducible clonus.1,4,5 Not all clinical findings might be present in a single patient. Presentation depends on mild, moderate or severe toxicity.4-6 Our patient was on a dual serotonergic drug regimen of a normal dose of venlafaxine and an overdose of sumatriptan, when he developed spontaneous clonus resulting in head shaking with only mild symptoms of serotonin toxicity (confer video in the full text).7 Signs of neuromuscular hyperreactivity such as clonus (spontaneous or inducible) with serial involuntary, rhythmic, muscular contractions and relaxations are the most important diagnostic findings also to distinguish from the neuroleptic malignant syndrome, anticholinergic and sympathomimetic toxicity, or CNS infections.4,6 Bilateral occurrence of clonus is not mandatory for the diagnosis of serotonin toxicity, however bilateral Babinski signs may occur.4 Clonus is typically more pronounced in the lower extremities in contrast to our patient's twitching of the head.4-6 However, previous observations described a "peculiar head-turning behavior characterized by repetitive rotation of the head" in patients with serotonin syndrome.5 Moreover animal studies found a link between head movements and the serotonin system, where the head-twitch response is induced by activation of serotonergic 5-ht receptors in rodents.8-10 Other mild cases of serotonin toxicity were found to be "afebrile but tachycardic and with twitching or tremor".6,11 Fever higher than 38*C was not as strongly associated with the diagnosis of the serotonin syndrome.1, 5 Otherwise temperature increase over 38.5*C usually caused by muscular hyperactivity indicated severe life-threatening cases of serotonin toxicity.1,4,5 In our patient with mild symptoms and low muscular hyperactivity the temperature was not elevated. Symptoms in our patient started shortly after increase of sumatriptan dosage and typically resolved within 24 hours after the discontinuation of serotonergic drugs and the initiation of symptomatic therapy with benzodiazepines. Synoptical with the timing of onset and resolution of symptoms, the pattern of illness, and the results of investigations to rule out alternative causes we established the diagnosis of a serotonin syndrome aka serotonin toxicity. We did not rechallenge the patient with the drug as a last option to attribute causality to the suspected adverse drug reaction.12

References

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4. http://www.uptodate.com/contents/serotonin-syndrome (accessed October 21, 2013).

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10. Fantegrossi WE, Simoneau J, Cohen MS, Zimmerman SM, Henson CM, Rice KC, Woods JH. Interaction of 5-HT2A and 5-HT2C receptors in R(-)-2,5- dimethoxy-4-iodoamphetamine-elicited head twitch behavior in mice. J Pharmacol Exp Ther 2010; 335:728-34.

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Conflict of Interest:

None declared