Editing Serotonin syndrome (section)

==Management==

Management is based primarily on stopping the usage of the precipitating drugs, the administration of [[serotonin antagonist]]s such as [[cyproheptadine]] (with a regimen of 12&nbsp;mg for the initial dose followed by 2&nbsp;mg every 2 hours until clinical, while some claim that a higher initial dose up to 32&nbsp;mg has more benefit<ref name="n860">{{cite journal | last=Prakash | first=Sanjay | last2=Shah | first2=Chetsi S. | last3=Prakash | first3=Anurag | title=Serotonin syndrome controversies: A need for consensus | journal=World Journal of Critical Care Medicine | volume=13 | issue=2 | date=2024-06-09 | issn=2220-3141 | pmid=38855279 | pmc=11155509 | doi=10.5492/wjccm.v13.i2.94707 | doi-access=free | page=94707}}</ref>),<ref name="Scotton Hill Williams Barnes 2019 p=117864691987392">{{cite journal | last1=Scotton | first1=William J | last2=Hill | first2=Lisa J | last3=Williams | first3=Adrian C | last4=Barnes | first4=Nicholas M | title=Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions | journal=International Journal of Tryptophan Research | publisher=SAGE Publications | volume=12 | year=2019 | issn=1178-6469 | doi=10.1177/1178646919873925 | page=117864691987392| pmid=31523132 | pmc=6734608 }}</ref> and supportive care including the control of agitation, the control of autonomic instability, and the control of hyperthermia.<ref name=Boy2005/><ref>{{cite journal|author=Sporer K |title=The serotonin syndrome. Implicated drugs, pathophysiology and management |journal=Drug Saf |volume=13 |issue=2 |pages=94–104 |year=1995 |pmid=7576268 |doi=10.2165/00002018-199513020-00004|s2cid=19809259 }}</ref><ref>{{cite journal | title=Recognition and treatment of serotonin syndrome | author=Frank, Christopher | pmc=2464814 | pmid=18625822 | volume=54 | issue=7 | year=2008 | journal=Can Fam Physician | pages=988–92}}</ref> Additionally, those who ingest large doses of serotonergic agents may benefit from gastrointestinal decontamination with [[activated charcoal]] if it can be administered within an hour of overdose.<ref name="Isbister Buckley"/> The intensity of therapy depends on the severity of symptoms. If the symptoms are mild, treatment may only consist of discontinuation of the offending medication or medications, offering supportive measures, giving [[benzodiazepine]]s for myoclonus, and waiting for the symptoms to resolve. Moderate cases should have all thermal and cardiorespiratory abnormalities corrected and can benefit from serotonin antagonists. The serotonin antagonist cyproheptadine is the recommended initial therapy, although there have been no [[controlled trials]] demonstrating its efficacy for SS.<ref name="Isbister Buckley"/><ref name="Graudins"/><ref>{{cite journal|author=Gillman PK |title=The serotonin syndrome and its treatment |journal=J Psychopharmacol (Oxford) |volume=13 |issue=1 |pages=100–9 |year=1999 |pmid=10221364 |doi=10.1177/026988119901300111|s2cid=17640246 |url=https://zenodo.org/record/844143 }}</ref> Despite the absence of controlled trials, there are a number of case reports detailing apparent improvement after people have been administered cyproheptadine.<ref name="Isbister Buckley"/> Animal experiments also suggest a benefit from serotonin antagonists.<ref>{{cite journal|vauthors=Nisijima K, Yoshino T, Yui K, Katoh S |title=Potent serotonin (5-HT)(2A) receptor antagonists completely prevent the development of hyperthermia in an animal model of the 5-HT syndrome |journal=Brain Res. |volume=890 |issue=1 |pages=23–31 |date=January 2001 |pmid=11164765 |doi=10.1016/S0006-8993(00)03020-1|s2cid=29995925 }}</ref> Cyproheptadine is only available as tablets and therefore can only be administered orally or via a [[nasogastric tube]]; it is unlikely to be effective in people administered activated charcoal and has limited use in severe cases.<ref name="Isbister Buckley"/> Cyproheptadine can be stopped when the person is no longer experiencing symptoms and the half life of serotonergic medications already passed.<ref name="Vol2013"/>

Additional pharmacological treatment for severe case includes administering atypical antipsychotic drugs with serotonin antagonist activity such as [[olanzapine]] or [[asenapine]].<ref name="Boy2005" /> Critically ill people should receive the above therapies as well as sedation or neuromuscular paralysis.<ref name="Boy2005" /> People who have autonomic instability such as low [[blood pressure]] require treatment with direct-acting sympathomimetics such as [[epinephrine]], norepinephrine, or [[phenylephrine]].<ref name="Boy2005" /> Conversely, hypertension or tachycardia can be treated with short-acting [[antihypertensive]] drugs such as [[nitroprusside]] or [[esmolol]]; longer acting drugs such as [[propranolol]] should be avoided as they may lead to hypotension and shock.<ref name="Boy2005" /> The cause of serotonin toxicity or accumulation is an important factor in determining the course of treatment. Serotonin is catabolized by [[monoamine oxidase&nbsp;A]] in the presence of [[oxygen]], so if care is taken to prevent an unsafe spike in body temperature or metabolic acidosis, oxygenation will assist in dispatching the excess serotonin. The same principle applies to alcohol intoxication. In cases of SS caused by MAOIs, oxygenation will not help to dispatch serotonin. In such instances, hydration is the main concern until the enzyme is regenerated.

===Agitation===
Specific treatment for some symptoms may be required. One of the most important treatments is the control of agitation due to the extreme possibility of injury to the person themselves or caregivers, benzodiazepines should be administered at first sign of this.<ref name=Boy2005/> [[Medical restraint|Physical restraints]] are not recommended for agitation or delirium as they may contribute to mortality by enforcing isometric [[muscle contraction]]s that are associated with severe [[lactic acidosis]] and hyperthermia. If physical restraints are necessary for severe agitation they must be rapidly replaced with pharmacological [[sedation]].<ref name=Boy2005/> The agitation can cause a large amount of muscle breakdown. This breakdown can cause severe damage to the kidneys through a condition called [[rhabdomyolysis]].<ref>{{cite web |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004531/ |title=Serotonin syndrome – PubMed Health |publisher=Ncbi.nlm.nih.gov |access-date=2013-01-28 |url-status=live |archive-url=https://web.archive.org/web/20130201070649/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0004531/ |archive-date=2013-02-01 }}</ref>

===Hyperthermia===
Treatment for hyperthermia includes reducing muscle overactivity via sedation with a benzodiazepine. More severe cases may require muscular paralysis with [[vecuronium]], [[intubation]], and artificial ventilation.<ref name=Boy2005/><ref name="Isbister Buckley"/> [[Suxamethonium]] is not recommended for muscular paralysis as it may increase the risk of cardiac dysrhythmia from hyperkalemia associated with rhabdomyolysis.<ref name=Boy2005/> [[Antipyretic]] agents are not recommended as the increase in [[body temperature]] is due to muscular activity, not a [[hypothalamic]] temperature set point abnormality.<ref name=Boy2005/>