Editing Serotonin syndrome (section)

==Diagnosis==

There is no specific test for SS. Diagnosis is by symptom observation and investigation of the person's history.<ref name=Boy2005/> Several criteria have been proposed. The first evaluated criteria were introduced in 1991 by Harvey Sternbach.<ref name=Boy2005/><ref name="Sternbach"/><ref name="pmid9684919">{{cite journal |vauthors=Hegerl U, Bottlender R, Gallinat J, Kuss HJ, Ackenheil M, Möller HJ |title=The serotonin syndrome scale: first results on validity |journal=Eur Arch Psychiatry Clin Neurosci |volume=248 |issue=2 |pages=96–103 |year=1998 |pmid=9684919 |doi=10.1007/s004060050024 |s2cid=37993326 |url=http://link.springer.de/link/service/journals/00406/bibs/8248002/82480096.htm |url-status=dead |archive-url=https://web.archive.org/web/19991011013705/http://link.springer.de/link/service/journals/00406/bibs/8248002/82480096.htm |archive-date=1999-10-11 }}</ref> Researchers later developed the Hunter Toxicity Criteria Decision Rules, which have better [[sensitivity and specificity]], 84% and 97%, respectively, when compared with the gold standard of diagnosis by a medical toxicologist.<ref name=Boy2005/><ref name="Dunkley"/> As of 2007, Sternbach's criteria were still the most commonly used.<ref name="Isbister Buckley"/>

The most important symptoms for diagnosing SS are tremor, extreme aggressiveness, [[akathisia]], or clonus (spontaneous, inducible and ocular).<ref name="Dunkley"/> [[Physical examination]] of the patient should include assessment of [[deep tendon reflex]]es and muscle rigidity, the dryness of the [[Mucous membrane|mucosa of the mouth]], the size and reactivity of the pupils, the intensity of bowel sounds, skin color, and the presence or absence of sweating.<ref name=Boy2005/> The patient's history also plays an important role in diagnosis, investigations should include inquiries about the use of prescription and [[over-the-counter drug]]s, illicit substances, and [[dietary supplement]]s, as all these agents have been implicated in the development of SS.<ref name=Boy2005/> To fulfill the Hunter Criteria, a patient must have taken a [[serotonergic agent]] and meet one of the following conditions:<ref name="Dunkley"/>
* Spontaneous clonus, or
* Inducible clonus plus agitation or [[Perspiration|diaphoresis]], or
* Ocular clonus plus agitation or diaphoresis, or
* [[Tremor]] plus [[hyperreflexia]], or
* Hypertonism plus temperature > {{convert|38|°C|°F}} plus ocular clonus or inducible clonus

===Differential diagnosis===

Serotonin toxicity has a characteristic picture which is generally hard to confuse with other [[medical conditions]], but in some situations it may go unrecognized because it may be mistaken for a [[viral illness]], [[anxiety disorder]]s, [[neurological disorder]], [[anticholinergic]] poisoning, [[sympathomimetic]] toxicity, or worsening psychiatric condition.<ref name=Boy2005/><ref name="Isbister Buckley"/><ref>{{cite journal|vauthors=Fennell J, Hussain M |title=Serotonin syndrome: case report and current concepts |journal=Ir Med J |volume=98 |issue=5 |pages=143–4 |year=2005 |pmid=16010782}}</ref> The condition most often confused with serotonin syndrome is [[neuroleptic malignant syndrome]] (NMS).<ref>{{cite book|vauthors=Nisijima K, Shioda K, Iwamura T |title=Neurobiology of Hyperthermia |chapter=Neuroleptic malignant syndrome and serotonin syndrome |journal=Prog Brain Res |volume=162 |pages=81–104 |year=2007 |pmid=17645916 |doi=10.1016/S0079-6123(06)62006-2 |series=Progress in Brain Research |isbn=9780444519269}}</ref><ref name="Tormoehlen">{{cite book |last1=Tormoehlen |first1=LM |last2=Rusyniak |first2=DE |title=Thermoregulation: From Basic Neuroscience to Clinical Neurology, Part II |chapter=Neuroleptic malignant syndrome and serotonin syndrome |series=Handbook of Clinical Neurology |date=2018 |volume=157 |pages=663–675 |doi=10.1016/B978-0-444-64074-1.00039-2 |pmid=30459031|isbn=9780444640741 }}</ref> The clinical features of neuroleptic malignant syndrome and SS share some features which can make differentiating them difficult.<ref>{{cite journal|vauthors=Christensen V, Glenthøj B |title=[Malignant neuroleptic syndrome or serotonergic syndrome] |journal=Ugeskrift for Lægerer |volume=163 |issue=3 |pages=301–2 |year=2001 |pmid=11219110}}</ref> In both conditions, [[Autonomic nervous system|autonomic]] dysfunction and altered [[mental status]] develop.<ref name="Whyte"/> However, they are actually very different conditions with different underlying dysfunction (serotonin excess vs dopamine blockade). Both the time course and the clinical features of NMS differ significantly from those of serotonin toxicity.<ref name="Dunkley"/> Serotonin toxicity has a rapid onset after the administration of a serotonergic drug and responds to serotonin blockade such as drugs like [[chlorpromazine]] and [[cyproheptadine]]. [[Dopamine receptor]] blockade (NMS) has a slow onset, typically evolves over several days after administration of a [[neuroleptic]] drug, and responds to dopamine agonists such as [[bromocriptine]].<ref name=Boy2005/><ref name="Whyte"/>

[[Differential diagnosis]] may become difficult in patients recently exposed to both serotonergic and neuroleptic drugs. [[Bradykinesia]] and [[extrapyramidal symptoms|extrapyramidal]] "lead pipe" rigidity are classically present in NMS, whereas SS causes [[hyperkinesia]] and clonus; these distinct symptoms can aid in differentiation.<ref name="Birmes">{{cite journal|vauthors=Birmes P, Coppin D, Schmitt L, Lauque D |title=Serotonin syndrome: a brief review |journal=CMAJ |volume=168 |issue=11 |pages=1439–42 |date=May 2003 |pmid=12771076 |pmc=155963 |url=http://www.cmaj.ca/cgi/pmidlookup?view=long&pmid=12771076}}</ref><ref>{{cite journal|vauthors=Isbister GK, Dawson A, Whyte IM |title=Citalopram overdose, serotonin toxicity, or neuroleptic malignant syndrome? |journal=Can J Psychiatry |volume=46 |issue=7 |pages=657–9 |date=September 2001 |pmid=11582830 |doi= 10.1177/070674370104600718|doi-access=free }}</ref>