Ver el código de «Serotonin syndrome»

==Background==
*Can be produced by any serotonergic medication
*1 in 6 U.S. adults take at least one psychoactive medication<ref>Moore TJ and Mattison DR. Adult Utilization of Psychiatric Drugs and Differences by Sex, Age, and Race. JAMA Intern Med. Published online December 12, 2016. doi:10.1001/jamainternmed.2016.7507.</ref>
*Majority of cases occur within therapeutic drug dosages
*Most common cause is ingestion of foods high in L-Tryptophan while taking an MAOI. Second most common is ingestion of both SSRI and MAOI<ref>Stork CM. Serotonin Reuptake Inhibitors and Atypical Antidepressants. In: Flomenbaum N, Goldfrank L, Hoffman R, Howland MA, et al, eds. Goldfrank’s Toxicologic Emergencies. 8th Ed. New York, NY: McGraw-Hill; 2006: 1070-1082</ref>
*Most common cause of death is severe hyperthermia

===Causative Agents<ref>Brown CH. Drug-induced Serotonin Syndrome. US Pharm. 2010;35(11):HS-16-HS-21.</ref>===
====Antidepressants====
*[[SSRIs]]
*[[SNRIs]]
*[[Bupropion]]<ref>Thorpe EL, Pizon AF, Lynch MJ, Boyer J. Bupropion induced serotonin syndrome: a case report. J Med Toxicol. 2010;6(2):168-171. doi:10.1007/s13181-010-0021-x</ref>
*[[Buspirone]]
*[[TCAs]]
*[[Lithium]]
*[[Mirtazapine]]
*[[Trazodone]]
*[[Valproic acid]]
*MAOIs (should have washout period of 2+ weeks prior to starting a SSRI)
**Phenelzine
**Selegiline
**Tranylcypromine

====Drugs of Abuse====
*[[Cocaine]]
*[[Ecstasy (MDMA)]]
*[[Methamphetamine]]
*[[LSD]]

====Analgesics====
*[[Fentanyl]]
*[[Meperidine]] (Demerol)
*[[Methadone]]
*[[Tramadol]]

====[[Antiemetics]]====
*[[Metoclopramide]]
*[[Ondansetron]]

====Over the counter Medications====
*[[Dextromethorphan]]
*Oral decongestants ([[Pseudoephedrine]])

====Herbal products====
*St John’s Wort, Ginseng, Nutmeg, Yohimbe

====Other Medications====
*Triptans
*Ergot alkaloids
*Bromocriptine
*[[Linezolid]]
*[[Carbamazepine]]
*[[Cyclobenzaprine]]
*L-tryptophan, 5-hydroxytryptophan
*[[Methylene blue]]

==Clinical Features==
*[[Altered mental status]]: Agitated delirium.  Patients generally hyperactive.
*Autonomic Instability: Hyperthermia, tachycardia, hypertension, diaphoresis, gastrointestinal illness <ref>Boyer, E. W. and Shannon, M. (2005) ‘The Serotonin Syndrome’, New England Journal of Medicine, 352(11), pp. 1112–1120. doi: 10.1056/nejmra041867</ref>
**Often labile blood pressure, HR
*Neuromuscular Abnormalities: Clonus, ocular clonus, myoclonus, rigidity, hyperreflexia, tremor, seizures
**More pronounced in the lower extremities
**Clonus (inducible or spontaneous): most common finding<ref>Farkas, J. Serotonin Syndrome. The Internet Book of Critical Care. https://emcrit.org/ibcc/serotonin/. Published June 13th, 2019. Accessed December 31st, 2020.</ref>
***Important to identify because it does not occur in other conditions that mimic serotonin syndrome
**Hyperactivity as opposed to rigidity in [[neuroleptic malignant syndrome]]

==Differential Diagnosis==
{{Movement disorder DDX}}
{{AMS and fever DDX}}

==Evaluation==
===Hunter Toxicity Criteria Decision Rules===
Serotonergic agent plus 1 of the following<ref>Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM 2003;96:635-642</ref>:
*Spontaneous clonus
*Inducible clonus AND (agitation or diaphoresis)
*Ocular Clonus AND (agitation or diaphoresis)
*Tremor AND hyperreflexia
*Hypertonia AND temperature >38 AND (ocular clonus or inducible clonus)

''84% Sn, 97% Sp''

{{Serotonin syndrome vs neuroleptic malignant syndrome}}

==Management==
*Discontinue all serotonergic drugs
*Aggressive supportive care
**If pressors required, direct acting (e.g. norepinephrine, epi) preferred, MAO inhibition causes erratic response to dopamine
*[[Benzos]]
**Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
**In severe cases, large doses are required (diazepam IV 10-20 mg, titrated with 10 mg increments)
*[[Cyproheptadine]]<ref>Graudins, A., Stearman, A. and Chan, B. (1998) ‘Treatment of the serotonin syndrome with cyproheptadine’, The Journal of Emergency Medicine, 16(4), pp. 615–619. doi: 10.1016/s0736-4679(98)00057-2</ref>
**Give if benzodiazepines and supportive care fail to improve agitation and abnormal vitals
**Serotonin antagonist
***Also has antihistamine and anticholinergic properties that may exacerbate other mixed toxicology picture
**Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
**Give 4mg q6hr x48hr if patient is responsive to initial dose
*[[Chlorpromazine]]<ref>Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109</ref>
**Phenothiazine with antiserotonergic effects
**50mg to 100mg IM
**Avoid in:
***Hemodynamically unstable patients as can cause serious hypotension<ref>Frank C. Recognition and treatment of serotonin syndrome. Can Fam Physician. 2008 Jul; 54(7): 988–992.</ref>
***Cases in which NMS may still be on the differential
*[[Dexmedetomidine]]<ref>Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014; 48(12):1651-1654.</ref><ref>Duggal HS, Fetchko J. Serotonin syndrome and atypical antipsychotics. Am J Psychiatry. 2002;159(4):672–3.</ref>
**Small case series found this helpful in adolescent cases refractory to benzos
*Dantrolene generally not recommended as it can worsen serotonin toxicity<ref>Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005 Mar 17; 352(11):1112-20.</ref>
*Treat hyperthermia
**Hyperthermia due to increase in muscular activity, not change in set point
**[[Intubate]] and paralyze if temperature > 41.1
**Standard [[cooling measures]]
***Fans, water sprays, ice packs, cooled crystalloids, cooling blankets

==Disposition==
*Severe cases may require [[intubation]] and [[ventilation]] in ICU
*24hr admission for [[altered mental status]] or abnormal [[vital signs]] requiring further supportive care
*Discharge mild cases with minimal intervention required after 6 hrs of observation

==See Also==
*[[Toxidromes]]

==References==
<references/>

[[Category:Toxicology]]