Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases

Abstract

BackgroundSerotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome’s main feature is neuro-muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history.MethodsSystematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science.ResultsTwo of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear-cut.ConclusionsOur findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be captured in any other way but through case reports.Electronic supplementary materialThe online version of this article (doi:10.1186/s12883-016-0616-1) contains supplementary material, which is available to authorized users.

The psychoactive drug 25B-NBOMe recapitulates rhabdomyolysis in zebrafish larvae

“…Serotonin syndrome is caused by the excessive activation of serotonin (5-hydroxytryptamine: 5-HT) receptors in the nervous system, and is characterized by autonomic hyperactivity, mental-status changes, and neuromuscular abnormalities including rhabdomyolysis [ 1 , 2 ]. Serotonin syndrome is known to be induced not only by diverse serotonergic drugs [i.e., monoamine oxidase (MAO) inhibitors, selective serotonin reuptake inhibitors (SSRIs) and the 5-HT precursor ( l -tryptophan)] and their combinations, but also by illegal drugs such as methylenedioxymethamphetamine (MDMA) [ 3 ].…”

Serotonin Syndrome in the Emergency Department

“…Several sets of diagnostic criteria have been developed to help define SS. Three sets of criteria have been validated for diagnosis: Sternbach, Hunter, and Radomski [4]. The Hunter criteria are the most accurate diagnostic set available to diagnose SS with a sensitivity of 84% and specificity of 97% [5].…”

Selective Serotonin Reuptake Inhibitors Induced Serotonin Syndrome –A Case Report

“…Drugs with direct or indirect serotonergic action stimulates 5HT 1A and 5HT 2 receptors and precipitates SS. 4 In mild cases the predominant features are diaphoresis, shivering, tachycardia, mild hypertension, mydriasis, myoclonus, tremor and hyperreflexia. In moderate syndrome hyperthermia (40˚ c), mild agitation, clonus, pressure speech, hyperactive bowel sounds and horizontal ocular clonus is seen.…”