Serotonin syndrome

Clinical triad

• Mental status changes
  • Apprehension, anxiety, agitation, psychomotor acceleration, delirium and confusion
• Autonomic stimulation
  • Diarrhoea, flushing, hypertension, hyperthermia, mydriasis, sweating, tachycardia
• Neuromuscular excitation
  • Clonus (esp. ocular and ankle), hyperreflexia, increased tone (lower limbs > upper limbs), myoclonus, rigidity and tremor
• Bold ones are significantly associated with diagnosis
• Hyperthermia seen in severe cases

Complications

• Rhabdo, renal failure, DIC and death

Introduction

• Classically symptoms arise within hours and resolve within 24-48 hours of discontinuation of agent
• Often develops within first 8 hours of deliberate self-poisoning and frequent after the patient has presented to hospital
• Clinical diagnosis and requires history of ingestion of one or more serotonergic agents, characteristic clinical features and high index of suspicion
• May arise in the setting of:
  • Introduction or increase in dose of single agent
  • Change in therapy from one serotonergic agent to another with inadequate washout period
  • Drug interaction between two agents
  • Interaction between serotonergic agent and illict drug or OTC preparation
  • Deliberate self-poisoning

Diagnostic algorithm

Agents

• Analgesics – Dextromethorphan, fentanyl, pethidine, tramadol
• TCA
• Amphetamines, MDMA
• Spirulina, St Johns Wort
• Lithium
• MAOi
• SSRI
• SNRI’s
• Tryptophan

Antidepressants

• Life-threatening = SSRI + MAOi
• Life-threatening serotonin syndrome does NOT occur after ingestion of a single SSRI

DDx

• Neuroleptic malignant syndrome
• Anticholinergic syndrome
• Malignant hyperthermia
• CNS infection
• Salicylate intoxication
• Theophylline intoxication
• Nicotine intoxication
• Sympathomimetic intoxication

Differential

Resuscitation

• If coma, recurrent seizures, temp >39.5 or severe rigidity compromising ventilation – I&V with ongoing paralysis
• IV benzo – Diazepam 5-10mg IV q3-5min for gentle sedation
• Hypertension and tachycardia usually respond promptly to benzodiazepines
• If refractory consider GTN or sodium nitroprusside infusion

Risk assessment

• Mild (normal vitals and mental status) usually self-resolves within hours
• More severe cases can be life threatening esp. if MAOi combined with SSRI
• Antidote therapy
  • Cyproheptadine
    • Antihistamine with antiserotonergic effects can be given orally or via NG
    • 8mg and if clinical response seen, repeat 8 hourly for 24 hours
  • Olanzapine
    • If agitation is a prominent feature
    • 5-10mg sublingual
  • Chlorpromazine
    • If agitation is a prominent feature
    • 25-100mg in 100mL N/S over 30-60min
    • Can have hypotension, sedation and anticholinergic side effects
  • Not indicate for severe serotonin syndrome when I&V, paralyis and cooling are the required therapies

Disposition

• If at risk of serotonin syndrome – observe at least 8 hours (12 hours if slow-release preparation) and never discharge overnight
• If any altered mental status or vital signs – observe, supportive care and consider serotonin antagonist therapy

Last Updated on October 13, 2020 by Andrew Crofton