Diferencia entre revisiones de «Serotonin syndrome»

(Added info on MAOIs)
(Strip excess bold)
 
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==Background==
==Background==
*Can be produced by any serotonergic medication
*Drug-induced excess serotonergic activity in CNS and peripheral nervous system
*Vast majority of cases occur within therapeutic dosages and often from exposure to several different serotonergic drugs that increase CNS serotonin activity simultaneously, like while switching between antidepressant classes or drugs.
*Usually results from combination of serotonergic agents or dose increase of a single agent
*Most common cause of death is severe hyperthermia
*Onset typically within 6-24 hours (usually within 6 hours of medication change)
*According to one study, the most commonly reported cause of serotonin syndrome was ingestion of foods large in L-Tryptophan, precursor of serotonin, along with MAOI, while the second most common cause was ingestion of 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>
*Mild cases are common; '''severe cases can be life-threatening'''
*Mortality ~2-12% in severe cases


===Causative Agents===
===Common Causative Agents===
*[[SSRIs]]
*SSRIs: fluoxetine, sertraline, paroxetine, citalopram, escitalopram
*MAOIs (have long duration of action a ‘washout’ period of at least two weeks should be instituted before starting a SSRI)
*SNRIs: venlafaxine, duloxetine
*TCAs
*MAOIs: phenelzine, tranylcypromine, selegiline, linezolid, methylene blue
*Drugs of Abuse: Cocaine, Ecstasy, Marijuana, Meth
*TCAs: amitriptyline, clomipramine
*Analgesics: Demerol, fentanyl
*Opioids: tramadol, meperidine (Demerol), fentanyl, methadone
*Antiemetics
*Triptans: sumatriptan (controversial, risk likely low)
*Triptans
*Other: dextromethorphan, [[lithium]], MDMA ("ecstasy"), cocaine, ondansetron (rare)
*Bromocriptine
*Most dangerous combination: MAOI + serotonergic agent
*OTC: Cough meds like [[Dextromethorphan]], herbal products, St John’s Wort


==Clinical Features==
==Clinical Features==
*[[Altered mental status]]: Agitated delirium
*Rapid onset (hours) — distinguishes from [[neuroleptic malignant syndrome]] (days)
*Autonomic Instability: Hyperthermia, Tachycardia, hypertension, diaphoresis <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>
*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):
**Often labile blood pressure, HR
**In setting of serotonergic agent + any ONE of:
*Neuromuscular Abnormalities: Myoclonus, ocular clonus, rigidity, hyperreflexia, tremor
***Spontaneous clonus (most important finding)
**More pronounced in the lower extremities
***Inducible clonus + agitation or diaphoresis
**Myoclonus: most common finding
***Ocular clonus + agitation or diaphoresis
***Important to identify because it does not occur in other conditions that mimic serotonin syndrome
***Tremor + hyperreflexia
***Hypertonia + temperature >38°C + ocular or inducible clonus
 
===Clinical Triad===
*Neuromuscular excitation: clonus (spontaneous, inducible, or ocular), hyperreflexia, tremor, myoclonus, rigidity (severe)
*Autonomic dysfunction: diaphoresis, [[tachycardia]], [[hyperthermia]], hypertension, mydriasis, hyperactive bowel sounds, diarrhea
*'''Altered mental status''': agitation, anxiety, confusion, delirium
 
===Severity Spectrum===
*Mild: tremor, hyperreflexia, tachycardia, diaphoresis
*Moderate: agitation, clonus, mydriasis, hyperthermia (≤40°C)
*Severe: hyperthermia >40°C, rigidity, seizures, [[rhabdomyolysis]], [[DIC]], cardiovascular collapse


==Differential Diagnosis==
==Differential Diagnosis==
{{AMS and fever DDX}}
{| class="wikitable"
|-
! Feature !! '''Serotonin Syndrome''' !! '''[[Neuroleptic malignant syndrome]]''' !! '''[[Anticholinergic toxicity]]''' !! '''[[Malignant hyperthermia]]'''
|-
| Onset || '''Hours''' || Days || Hours || Minutes (OR)
|-
| Key finding || '''Clonus/hyperreflexia''' || Lead-pipe rigidity || Mydriasis, dry || Generalized rigidity
|-
| Bowel sounds || '''Hyperactive''' || Normal/decreased || '''Absent''' || Normal
|-
| Skin || Diaphoresis || Diaphoresis || '''Dry, flushed''' || Mottled
|-
| Pupils || Mydriasis || Normal || Mydriasis || Normal
|-
| CK || Mildly elevated || >1000 || Normal || Markedly elevated
|}
 
==Evaluation==
*Clinical diagnosis based on Hunter criteria — no confirmatory lab test
*CK: mildly elevated (markedly elevated if severe → [[rhabdomyolysis]])
*BMP: electrolytes, creatinine (renal injury), bicarbonate (acidosis)
*CBC, LFTs
*Lactate
*Coagulation studies (DIC in severe cases)
*Core temperature
*Medication reconciliation is essential — identify all serotonergic agents


==Diagnosis==
==Management==
===Hunter Toxicity Criteria Decision Rules===
===Immediate===
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>:
*Discontinue ALL serotonergic agents
*Spontaneous clonus
*Most mild cases resolve within 24-72 hours after drug cessation
*Inducible clonus AND (agitation or diaphoresis)
*Ocular Clonus AND (agitation or diaphoresis)
*Tremor AND hyperreflexia
*Hypertonia AND temp >38 AND (ocular clonus or inducible clonus)


''84% Sn, 97% Sp''
===Mild (Tremor, Hyperreflexia)===
*Observation, IV fluids, benzodiazepines PRN for agitation
*Supportive care


==Management==
===Moderate (Agitation, Clonus, Hyperthermia <40°C)===
*Discontinue all serotonergic drugs
*Benzodiazepines for agitation and autonomic instability:
*Aggressive supportive care
**Lorazepam 2-4 mg IV q5-10min, or midazolam
**If pressors required, direct acting (e.g. norepi, epi) preferred, MAO inhibition causes erratic response to dopamine
*Active cooling for hyperthermia (evaporative cooling, ice packs)
*[[Benzos]]
*IV fluid resuscitation
**Goal is to eliminate agitation, neuromuscular abnormalities, elevations in HR/BP
 
*[[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>
===Severe (Hyperthermia >40°C, Rigidity, Seizures)===
**Give if benzos and supportive care fail to improve agitation and abnormal vitals
*Cyproheptadine (serotonin antagonist):
**Serotonin antagonist
**12 mg PO/NG initial dose, then 2 mg q2h until clinical improvement
**Give 12mg PO/NG; repeat with 2mg q2hr until clinical response is seen (max 32mg/d)
**Maintenance: 8 mg PO q6h
**Give 4mg q6hr x48hr if pt is responsive to initial dose
**Only available PO/NG — '''crush and give via NG if intubated'''
*[[Chlorpromazine]]<ref>Gillman PK. The serotonin syndrome and its treatment. J Psychopharmacol 1999;13:100-109</ref>
*'''Intubation with neuromuscular blockade''' for severe rigidity/hyperthermia
**Phenothiazine with antiserotonergic effects
**Use non-depolarizing agent (avoid succinylcholine if hyperkalemia/rhabdomyolysis risk)
**50mg to 100mg IM
*Aggressive cooling
**Can consider in severe cases
*Benzodiazepines for seizures
*[[Dexmedetomidine]]<ref>Rushton WF, Charlton NP. Dexmedetomidine in the treatment of serotonin syndrome. Ann Pharmacother. 2014; 48(12):1651-1654.</ref>
 
**Small case series found this helpful in adolescent cases refractory to benzos
===What to Avoid===
*Treat hyperthermia
*NO antipyretics (not effective — hyperthermia is from muscle activity, not altered setpoint)
**Hyperthermia due to increase in muscular activity, not change in set point
*NO bromocriptine (for NMS, not SS)
**[[Intubate]] and paralyze if temp > 41.1
*NO dantrolene (limited role; rigidity in SS is different from NMS)
**Standard [[cooling measures]]
*Avoid restraints alone without chemical sedation (isometric muscle contraction worsens hyperthermia)


==Disposition==
==Disposition==
*Discharge mild cases with symptomatic treatment
*Mild: observe 6-12 hours; discharge if improving after drug cessation
*24hr admission for [[AMS]] or abnormal [[vital signs]] requiring further supportive care
*Moderate: admit to monitored bed
*Severe cases may require [[intubation]] and [[ventilation]] in ICU
*Severe: ICU admission
*Symptoms typically resolve within 24-72 hours (longer for fluoxetine/MAOIs — longer half-life)
*Before restarting serotonergic medications: allow washout period (5 half-lives)
**Fluoxetine: 5 weeks; MAOIs: 2 weeks


==See Also==
==See Also==
*[[Toxidromes]]
*[[Neuroleptic malignant syndrome]]
*[[Anticholinergic toxicity]]
*[[Malignant hyperthermia]]
*[[Toxicology]]
*[[MAOI toxicity]]


==References==
==References==
<references/>
<references/>
*Boyer EW, Shannon M. The serotonin syndrome. ''N Engl J Med''. 2005;352(11):1112-1120. PMID 15784664
*Isbister GK, et al. Serotonin toxicity: a practical approach to diagnosis and treatment. ''Med J Aust''. 2007;187(6):361-365. PMID 17874986
*Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. ''Am Fam Physician''. 2010;81(9):1139-1142. PMID 20433130


[[Category:Tox]]
[[Category:Toxicology]]
[[Category:Psychiatry]]

Revisión actual - 09:30 22 mar 2026

Background

  • 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
  • Onset typically within 6-24 hours (usually within 6 hours of medication change)
  • Mild cases are common; severe cases can be life-threatening
  • Mortality ~2-12% in severe cases

Common Causative Agents

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

Clinical Features

  • Rapid onset (hours) — distinguishes from neuroleptic malignant syndrome (days)
  • Hunter Serotonin Toxicity Criteria[1] (most sensitive/specific):
    • In setting of serotonergic agent + any ONE of:
      • Spontaneous clonus (most important finding)
      • Inducible clonus + agitation or diaphoresis
      • Ocular clonus + agitation or diaphoresis
      • Tremor + hyperreflexia
      • Hypertonia + temperature >38°C + ocular or inducible clonus

Clinical Triad

  • Neuromuscular excitation: clonus (spontaneous, inducible, or ocular), hyperreflexia, tremor, myoclonus, rigidity (severe)
  • Autonomic dysfunction: diaphoresis, tachycardia, hyperthermia, hypertension, mydriasis, hyperactive bowel sounds, diarrhea
  • Altered mental status: agitation, anxiety, confusion, delirium

Severity Spectrum

  • Mild: tremor, hyperreflexia, tachycardia, diaphoresis
  • Moderate: agitation, clonus, mydriasis, hyperthermia (≤40°C)
  • Severe: hyperthermia >40°C, rigidity, seizures, rhabdomyolysis, DIC, cardiovascular collapse

Differential Diagnosis

Feature Serotonin Syndrome Neuroleptic malignant syndrome Anticholinergic toxicity Malignant hyperthermia
Onset Hours Days Hours Minutes (OR)
Key finding Clonus/hyperreflexia Lead-pipe rigidity Mydriasis, dry Generalized rigidity
Bowel sounds Hyperactive Normal/decreased Absent Normal
Skin Diaphoresis Diaphoresis Dry, flushed Mottled
Pupils Mydriasis Normal Mydriasis Normal
CK Mildly elevated >1000 Normal Markedly elevated

Evaluation

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

Management

Immediate

  • Discontinue ALL serotonergic agents
  • Most mild cases resolve within 24-72 hours after drug cessation

Mild (Tremor, Hyperreflexia)

  • Observation, IV fluids, benzodiazepines PRN for agitation
  • Supportive care

Moderate (Agitation, Clonus, Hyperthermia <40°C)

  • Benzodiazepines for agitation and autonomic instability:
    • Lorazepam 2-4 mg IV q5-10min, or midazolam
  • Active cooling for hyperthermia (evaporative cooling, ice packs)
  • IV fluid resuscitation

Severe (Hyperthermia >40°C, Rigidity, Seizures)

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

What to Avoid

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

Disposition

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

See Also

References

  1. ↑ Dunkley EJ, et al. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules. QJM. 2003;96(9):635-642. PMID 12925718
  • Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med. 2005;352(11):1112-1120. PMID 15784664
  • Isbister GK, et al. Serotonin toxicity: a practical approach to diagnosis and treatment. Med J Aust. 2007;187(6):361-365. PMID 17874986
  • Ables AZ, Nagubilli R. Prevention, recognition, and management of serotonin syndrome. Am Fam Physician. 2010;81(9):1139-1142. PMID 20433130
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