Diferencia entre revisiones de «Serotonin syndrome»

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


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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