What is the treatment approach for a Selective Serotonin Reuptake Inhibitor (SSRI) overdose?

Treatment Approach for SSRI Overdose

The treatment of SSRI overdose requires immediate discontinuation of all serotonergic medications, supportive care, and administration of cyproheptadine in moderate to severe cases. 1

Initial Assessment and Triage

• Severity assessment:

  • Mild symptoms: Vomiting, somnolence (arousable with speaking voice or light touch), mydriasis, diaphoresis 2
  • Moderate to severe symptoms: Mental status changes, neuromuscular abnormalities (tremor, hyperreflexia, clonus), autonomic hyperactivity (hyperthermia, tachycardia, hypertension) 1

• Immediate referral to emergency department for:

  • Any patient with suicidal intent or intentional abuse 2
  • Any patient experiencing symptoms beyond mild effects 2
  • Any suspected serotonin syndrome (characterized by mental status changes, neuromuscular abnormalities, and autonomic hyperactivity) 1

Treatment Protocol

1. Supportive Care (First Line)

• Airway management: Approximately 25% of patients with serotonin syndrome require intubation and mechanical ventilation 1
• Intravenous fluids: For hydration and management of hyperthermia 1
• Benzodiazepines: First-line agent for agitation, muscle hyperactivity, and seizures 1, 2
• External cooling measures: For hyperthermia (>104°F/40°C) 1, 2
• Do not induce emesis 2

2. Specific Pharmacological Intervention

• Cyproheptadine (serotonin 5-HT2A antagonist):
  • Indicated for moderate to severe cases of serotonin syndrome 1
  • Initial dose: 12 mg orally
  • Maximum daily dose: 32 mg 1
  • Note: Diphenhydramine should NOT be used as a substitute 1

3. Cardiac Monitoring

• ECG monitoring: Particularly important for citalopram overdose, which is significantly associated with QTc prolongation 3
• Continuous vital sign monitoring: Essential for all moderate to severe cases 1

Special Considerations

Risk Stratification

• Low risk: Asymptomatic patients or those with mild effects following isolated unintentional acute SSRI ingestions of up to five times an initial adult therapeutic dose can be observed at home with instructions to call if symptoms develop 2

  • Citalopram ≤100 mg
  • Escitalopram ≤50 mg
  • Fluoxetine ≤100 mg
  • Fluvoxamine ≤250 mg
  • Paroxetine ≤100 mg
  • Sertraline ≤250 mg

• High risk:

  • Ingestions >75 times the common daily dose may result in serious adverse events including seizures, ECG changes, and decreased consciousness 4
  • Citalopram overdose requires particular attention due to significant QTc prolongation risk 3
  • Co-ingestion with other substances significantly increases toxicity 4

Laboratory Monitoring

• Complete blood count, electrolytes, BUN, creatinine
• Arterial blood gas in severe cases
• Liver function tests, creatine kinase
• Coagulation studies 1

Complications to Monitor

• Rhabdomyolysis
• Metabolic acidosis
• Elevated liver enzymes
• Renal failure
• Seizures
• Disseminated intravascular coagulation 1

Prognosis

The prognosis for isolated SSRI overdose with appropriate treatment is excellent. SSRIs are rarely fatal in overdose when taken alone, with most moderate overdoses (up to 30 times the common daily dose) associated with minor or no symptoms 4. However, mortality increases significantly when SSRIs are combined with other substances, particularly alcohol or other medications 4.

Important Caveats

• Avoid physical restraints as they may worsen hyperthermia and lactic acidosis 1
• SSRIs have a greater margin of safety in overdose compared to tricyclic antidepressants, but deaths have been reported following very large ingestions 5
• The mortality rate for serotonin syndrome is approximately 11% when not promptly treated 1
• Almost all fatalities involving SSRIs have involved co-ingestion of other substances 4