Serotonin syndrome - Revision history

Danbot: Strip excess bold

2026-03-22T09:30:55Z

Strip excess bold

← Older revision		Revision as of 09:30, 22 March 2026
Line 1:		Line 1:
	==Background==		==Background==
	*~~'''~~Drug-induced excess serotonergic activity~~'''~~ in CNS and peripheral nervous system		*Drug-induced excess serotonergic activity in CNS and peripheral nervous system
	*Usually results from ~~'''~~combination of serotonergic agents~~'''~~ or ~~'''~~dose increase~~'''~~ of a single agent		*Usually results from combination of serotonergic agents or dose increase of a single agent
	*Onset typically within ~~'''~~6-24 hours~~'''~~ (usually within 6 hours of medication change)		*Onset typically within 6-24 hours (usually within 6 hours of medication change)
	*Mild cases are common; '''severe cases can be life-threatening'''		*Mild cases are common; '''severe cases can be life-threatening'''
	*Mortality ~2-12% in severe cases		*Mortality ~2-12% in severe cases

	===Common Causative Agents===		===Common Causative Agents===
	*~~'''~~SSRIs~~'''~~: fluoxetine, sertraline, paroxetine, citalopram, escitalopram		*SSRIs: fluoxetine, sertraline, paroxetine, citalopram, escitalopram
	*~~'''~~SNRIs~~'''~~: venlafaxine, duloxetine		*SNRIs: venlafaxine, duloxetine
	*~~'''~~MAOIs~~'''~~: phenelzine, tranylcypromine, selegiline, linezolid, methylene blue		*MAOIs: phenelzine, tranylcypromine, selegiline, linezolid, methylene blue
	*~~'''~~TCAs~~'''~~: amitriptyline, clomipramine		*TCAs: amitriptyline, clomipramine
	*~~'''~~Opioids~~'''~~: ~~'''~~tramadol~~'''~~, ~~'''~~meperidine~~'''~~ (Demerol), fentanyl, methadone		*Opioids: tramadol, meperidine (Demerol), fentanyl, methadone
	*~~'''~~Triptans~~'''~~: sumatriptan (controversial, risk likely low)		*Triptans: sumatriptan (controversial, risk likely low)
	*~~'''~~Other~~'''~~: dextromethorphan, [[lithium]], MDMA ("ecstasy"), cocaine, ondansetron (rare)		*Other: dextromethorphan, [[lithium]], MDMA ("ecstasy"), cocaine, ondansetron (rare)
	*~~'''~~Most dangerous combination: MAOI + serotonergic agent~~'''~~		*Most dangerous combination: MAOI + serotonergic agent

	==Clinical Features==		==Clinical Features==
	*~~'''~~Rapid onset~~'''~~ (hours) — distinguishes from [[neuroleptic malignant syndrome]] (days)		*Rapid onset (hours) — distinguishes from [[neuroleptic malignant syndrome]] (days)
	*~~'''~~Hunter Serotonin Toxicity Criteria~~'''~~<ref>Dunkley EJ, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules. ''QJM''. 2003;96(9):635-642. PMID 12925718</ref> (most sensitive/specific):		*Hunter Serotonin Toxicity Criteria<ref>Dunkley EJ, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules. ''QJM''. 2003;96(9):635-642. PMID 12925718</ref> (most sensitive/specific):
	**In setting of serotonergic agent + ~~'''~~any ONE of~~'''~~:		**In setting of serotonergic agent + any ONE of:
	***~~'''~~Spontaneous clonus~~'''~~ (most important finding)		***Spontaneous clonus (most important finding)
	***~~'''~~Inducible clonus + agitation or diaphoresis~~'''~~		***Inducible clonus + agitation or diaphoresis
	***~~'''~~Ocular clonus + agitation or diaphoresis~~'''~~		***Ocular clonus + agitation or diaphoresis
	***Tremor + hyperreflexia		***Tremor + hyperreflexia
	***Hypertonia + temperature >38°C + ocular or inducible clonus		***Hypertonia + temperature >38°C + ocular or inducible clonus

	===Clinical Triad===		===Clinical Triad===
	*~~'''~~Neuromuscular excitation~~'''~~: ~~'''~~clonus~~'''~~ (spontaneous, inducible, or ocular), hyperreflexia, tremor, myoclonus, rigidity (severe)		*Neuromuscular excitation: clonus (spontaneous, inducible, or ocular), hyperreflexia, tremor, myoclonus, rigidity (severe)
	*~~'''~~Autonomic dysfunction~~'''~~: diaphoresis, [[tachycardia]], [[hyperthermia]], hypertension, mydriasis, ~~'''~~hyperactive bowel sounds~~'''~~, diarrhea		*Autonomic dysfunction: diaphoresis, [[tachycardia]], [[hyperthermia]], hypertension, mydriasis, hyperactive bowel sounds, diarrhea
	*'''Altered mental status''': agitation, anxiety, confusion, delirium		*'''Altered mental status''': agitation, anxiety, confusion, delirium

	===Severity Spectrum===		===Severity Spectrum===
	*~~'''~~Mild~~'''~~: tremor, hyperreflexia, tachycardia, diaphoresis		*Mild: tremor, hyperreflexia, tachycardia, diaphoresis
	*~~'''~~Moderate~~'''~~: agitation, clonus, mydriasis, hyperthermia (≤40°C)		*Moderate: agitation, clonus, mydriasis, hyperthermia (≤40°C)
	*~~'''~~Severe~~'''~~: hyperthermia >40°C, rigidity, seizures, [[rhabdomyolysis]], [[DIC]], ~~'''~~cardiovascular collapse~~'''~~		*Severe: hyperthermia >40°C, rigidity, seizures, [[rhabdomyolysis]], [[DIC]], cardiovascular collapse

	==Differential Diagnosis==		==Differential Diagnosis==
Line 55:		Line 55:

	==Evaluation==		==Evaluation==
	*~~'''~~Clinical diagnosis~~'''~~ based on Hunter criteria — no confirmatory lab test		*Clinical diagnosis based on Hunter criteria — no confirmatory lab test
	*~~'''~~CK~~'''~~: mildly elevated (markedly elevated if severe → [[rhabdomyolysis]])		*CK: mildly elevated (markedly elevated if severe → [[rhabdomyolysis]])
	*~~'''~~BMP~~'''~~: electrolytes, creatinine (renal injury), bicarbonate (acidosis)		*BMP: electrolytes, creatinine (renal injury), bicarbonate (acidosis)
	*~~'''~~CBC, LFTs~~'''~~		*CBC, LFTs
	*~~'''~~Lactate~~'''~~		*Lactate
	*~~'''~~Coagulation studies~~'''~~ (DIC in severe cases)		*Coagulation studies (DIC in severe cases)
	*~~'''~~Core temperature~~'''~~		*Core temperature
	*~~'''~~Medication reconciliation is essential~~'''~~ — identify all serotonergic agents		*Medication reconciliation is essential — identify all serotonergic agents

	==Management==		==Management==
	===Immediate===		===Immediate===
	*~~'''~~Discontinue ALL serotonergic agents~~'''~~		*Discontinue ALL serotonergic agents
	*Most mild cases resolve within ~~'''~~24-72 hours~~'''~~ after drug cessation		*Most mild cases resolve within 24-72 hours after drug cessation

	===Mild (Tremor, Hyperreflexia)===		===Mild (Tremor, Hyperreflexia)===
Line 74:		Line 74:

	===Moderate (Agitation, Clonus, Hyperthermia <40°C)===		===Moderate (Agitation, Clonus, Hyperthermia <40°C)===
	*~~'''~~Benzodiazepines~~'''~~ for agitation and autonomic instability:		*Benzodiazepines for agitation and autonomic instability:
	**~~'''~~Lorazepam 2-4 mg IV~~'''~~ q5-10min, or midazolam		**Lorazepam 2-4 mg IV q5-10min, or midazolam
	*Active cooling for hyperthermia (evaporative cooling, ice packs)		*Active cooling for hyperthermia (evaporative cooling, ice packs)
	*IV fluid resuscitation		*IV fluid resuscitation

	===Severe (Hyperthermia >40°C, Rigidity, Seizures)===		===Severe (Hyperthermia >40°C, Rigidity, Seizures)===
	*~~'''~~Cyproheptadine~~'''~~ (serotonin antagonist):		*Cyproheptadine (serotonin antagonist):
	**~~'''~~12 mg PO/NG initial dose~~'''~~, then ~~'''~~2 mg q2h~~'''~~ until clinical improvement		**12 mg PO/NG initial dose, then 2 mg q2h until clinical improvement
	**Maintenance: ~~'''~~8 mg PO q6h~~'''~~		**Maintenance: 8 mg PO q6h
	**Only available PO/NG — '''crush and give via NG if intubated'''		**Only available PO/NG — '''crush and give via NG if intubated'''
	*'''Intubation with neuromuscular blockade''' for severe rigidity/hyperthermia		*'''Intubation with neuromuscular blockade''' for severe rigidity/hyperthermia
	**Use ~~'''~~non-depolarizing agent~~'''~~ (avoid succinylcholine if hyperkalemia/rhabdomyolysis risk)		**Use non-depolarizing agent (avoid succinylcholine if hyperkalemia/rhabdomyolysis risk)
	*~~'''~~Aggressive cooling~~'''~~		*Aggressive cooling
	*~~'''~~Benzodiazepines for seizures~~'''~~		*Benzodiazepines for seizures

	===What to Avoid===		===What to Avoid===
	*~~'''~~NO antipyretics~~'''~~ (not effective — hyperthermia is from muscle activity, not altered setpoint)		*NO antipyretics (not effective — hyperthermia is from muscle activity, not altered setpoint)
	*~~'''~~NO bromocriptine~~'''~~ (for NMS, not SS)		*NO bromocriptine (for NMS, not SS)
	*~~'''~~NO dantrolene~~'''~~ (limited role; rigidity in SS is different from NMS)		*NO dantrolene (limited role; rigidity in SS is different from NMS)
	*~~'''~~Avoid restraints alone~~'''~~ without chemical sedation (isometric muscle contraction worsens hyperthermia)		*Avoid restraints alone without chemical sedation (isometric muscle contraction worsens hyperthermia)

	==Disposition==		==Disposition==
	*~~'''~~Mild~~'''~~: observe 6-12 hours; discharge if improving after drug cessation		*Mild: observe 6-12 hours; discharge if improving after drug cessation
	*~~'''~~Moderate~~'''~~: admit to monitored bed		*Moderate: admit to monitored bed
	*~~'''~~Severe~~'''~~: ICU admission		*Severe: ICU admission
	*Symptoms typically resolve within ~~'''~~24-72 hours~~'''~~ (longer for fluoxetine/MAOIs — longer half-life)		*Symptoms typically resolve within 24-72 hours (longer for fluoxetine/MAOIs — longer half-life)
	*Before restarting serotonergic medications: allow ~~'''~~washout period~~'''~~ (5 half-lives)		*Before restarting serotonergic medications: allow washout period (5 half-lives)
	**Fluoxetine: 5 weeks; MAOIs: 2 weeks		**Fluoxetine: 5 weeks; MAOIs: 2 weeks

Danbot: Major update: Hunter criteria, NMS comparison table, cyproheptadine dosing, severity-based management, washout periods, causative agents list, avoid dantrolene/antipyretics, references with PMIDs

2026-03-21T19:57:10Z

Major update: Hunter criteria, NMS comparison table, cyproheptadine dosing, severity-based management, washout periods, causative agents list, avoid dantrolene/antipyretics, references with PMIDs

Show changes

Danbot: Add MedicationDose SMW annotations (diazepam, cyproheptadine); dosing verified

2026-03-20T16:32:06Z

Add MedicationDose SMW annotations (diazepam, cyproheptadine); dosing verified

← Older revision		Revision as of 16:32, 20 March 2026
Line 115:		Line 115:
	*Discharge mild cases with minimal intervention required after 6 hrs of observation		*Discharge mild cases with minimal intervention required after 6 hrs of observation


			<div style="display:none">
			<!-- SMW MedicationDose annotations for serotonin syndrome medications -->
			{{MedicationDose\|drug=Diazepam\|dose=10-20 mg IV, titrate with 10 mg increments\|route=IV\|context=Benzodiazepine for agitation/neuromuscular abnormalities\|indication=Serotonin syndrome\|notes=Goal: eliminate agitation, neuromuscular abnormalities, HR/BP elevations}}
			{{MedicationDose\|drug=Cyproheptadine\|dose=12 mg PO/NG initial, then 2 mg q2h until response (max 32 mg/day); then 4 mg q6h x48h\|route=PO/NG\|context=Serotonin antagonist (if benzos and supportive care fail)\|indication=Serotonin syndrome\|max_dose=32 mg/day\|notes=Also has antihistamine and anticholinergic properties}}
			</div>
	==See Also==		==See Also==
	*[[Toxidromes]]		*[[Toxidromes]]

Rossdonaldson1: /* Video */

2024-04-17T20:10:53Z

Video

← Older revision		Revision as of 20:10, 17 April 2024
Line 117:		Line 117:
	==See Also==		==See Also==
	*[[Toxidromes]]		*[[Toxidromes]]

	~~==Video==~~
	~~{{#widget:YouTube\|id=nicowGCfm30}}~~

	==References==		==References==

Jonwarren: /* Management */

2021-03-14T16:50:42Z

Management

← Older revision		Revision as of 16:50, 14 March 2021
Line 108:		Line 108:
	**[[Intubate]] and paralyze if temperature > 41.1		**[[Intubate]] and paralyze if temperature > 41.1
	**Standard [[cooling measures]]		**Standard [[cooling measures]]
			***Fans, water sprays, ice packs, cooled crystalloids, cooling blankets

	==Disposition==		==Disposition==

Elcatracho: /* Antidepressants */

2021-02-03T19:41:47Z

Antidepressants

← Older revision		Revision as of 19:41, 3 February 2021
Line 10:		Line 10:
	*[[SSRIs]]		*[[SSRIs]]
	*[[SNRIs]]		*[[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]]		*[[Buspirone]]
	*[[TCAs]]		*[[TCAs]]

Elcatracho: /* Clinical Features */

2021-01-15T18:53:18Z

Clinical Features

← Older revision		Revision as of 18:53, 15 January 2021
Line 58:		Line 58:
	*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>		*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		**Often labile blood pressure, HR
	*Neuromuscular Abnormalities: Clonus, ocular clonus, rigidity, hyperreflexia, tremor, seizures		*Neuromuscular Abnormalities: Clonus, ocular clonus, myoclonus, rigidity, hyperreflexia, tremor, seizures
	**More pronounced in the lower extremities		**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>		**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>

Elcatracho: /* Clinical Features */

2021-01-01T05:49:11Z

Clinical Features

← Older revision		Revision as of 05:49, 1 January 2021
Line 58:		Line 58:
	*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>		*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		**Often labile blood pressure, HR
	*Neuromuscular Abnormalities: ~~Myoclonus~~, ocular clonus, rigidity, hyperreflexia, tremor, seizures		*Neuromuscular Abnormalities: Clonus, ocular clonus, rigidity, hyperreflexia, tremor, seizures
	**More pronounced in the lower extremities		**More pronounced in the lower extremities
	**~~Myoclonus~~ (inducible or spontaneous): most common finding		**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		***Important to identify because it does not occur in other conditions that mimic serotonin syndrome
	**Hyperactivity as opposed to rigidity in [[neuroleptic malignant syndrome]]		**Hyperactivity as opposed to rigidity in [[neuroleptic malignant syndrome]]

Rossdonaldson1: /* Causative AgentsBrown CH. Drug-induced Serotonin Syndrome. US Pharm. 2010;35(11):HS-16-HS-21. */

2020-11-14T13:42:22Z

Causative AgentsBrown CH. Drug-induced Serotonin Syndrome. US Pharm. 2010;35(11):HS-16-HS-21.

← Older revision		Revision as of 13:42, 14 November 2020
Line 6:		Line 6:
	*Most common cause of death is severe hyperthermia		*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>==		===Causative Agents<ref>Brown CH. Drug-induced Serotonin Syndrome. US Pharm. 2010;35(11):HS-16-HS-21.</ref>===
	===Antidepressants===		====Antidepressants====
	*[[SSRIs]]		*[[SSRIs]]
	*[[SNRIs]]		*[[SNRIs]]
Line 20:		Line 20:
	**Selegiline		**Selegiline
	**Tranylcypromine		**Tranylcypromine
	===Drugs of Abuse===
			====Drugs of Abuse====
	*[[Cocaine]]		*[[Cocaine]]
	*[[Ecstasy (MDMA)]]		*[[Ecstasy (MDMA)]]
Line 26:		Line 27:
	*[[LSD]]		*[[LSD]]

	===Analgesics===		====Analgesics====
	*[[Fentanyl]]		*[[Fentanyl]]
	*[[Meperidine]] (Demerol)		*[[Meperidine]] (Demerol)
	*[[Methadone]]		*[[Methadone]]
	*[[Tramadol]]		*[[Tramadol]]
	===[[Antiemetics]]===
			====[[Antiemetics]]====
	*[[Metoclopramide]]		*[[Metoclopramide]]
	*[[Ondansetron]]		*[[Ondansetron]]
	===Over the counter Medications===
			====Over the counter Medications====
	*[[Dextromethorphan]]		*[[Dextromethorphan]]
	*Oral decongestants ([[Pseudoephedrine]])		*Oral decongestants ([[Pseudoephedrine]])

	===Herbal products===		====Herbal products====
	*St John’s Wort, Ginseng, Nutmeg, Yohimbe		*St John’s Wort, Ginseng, Nutmeg, Yohimbe
	===Other Medications===
			====Other Medications====
	*Triptans		*Triptans
	*Ergot alkaloids		*Ergot alkaloids

Rossdonaldson1: /* Differential Diagnosis */

2020-11-14T13:41:34Z

Differential Diagnosis

← Older revision		Revision as of 13:41, 14 November 2020
Line 61:		Line 61:

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