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

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Treatment of SSRI Overdose

The treatment of SSRI overdose requires immediate supportive care, with particular attention to airway, breathing, and circulation, while monitoring for and managing serotonin syndrome, which is the most serious potential complication. 1

Initial Assessment and Management

  • Triage Decision:

    • All patients with intentional overdose, suicidal intent, or suspected malicious intent should be referred to an emergency department regardless of dose 2
    • Patients with symptoms beyond mild effects (mild effects include vomiting, mild somnolence, mydriasis, or diaphoresis) should be transported to an emergency department 2
  • Asymptomatic patients:

    • Can be observed at home if the ingestion was unintentional and less than five times an initial adult therapeutic dose:
      • Citalopram: ≤100 mg
      • Escitalopram: ≤50 mg
      • Fluoxetine: ≤100 mg
      • Fluvoxamine: ≤250 mg
      • Paroxetine: ≤100 mg
      • Sertraline: ≤250 mg 2

Emergency Department Management

Supportive Care

  • Secure airway, breathing, and circulation
  • Cardiac monitoring (particularly for citalopram overdose due to risk of QTc prolongation) 3
  • Intravenous access
  • Monitor vital signs with particular attention to temperature (hyperthermia may indicate serotonin syndrome)

Decontamination

  • Do not induce emesis 2
  • Consider activated charcoal if:
    • Presentation is within 1 hour of ingestion
    • Patient is alert and able to protect airway
    • No contraindications exist 2

Management of Specific Complications

Serotonin Syndrome

Serotonin syndrome occurs in approximately 14% of SSRI overdoses 3 and is characterized by:

  • Mental status changes (confusion, agitation, anxiety)
  • Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity)
  • Autonomic hyperactivity (hypertension, tachycardia, hyperthermia, diaphoresis) 1

Treatment of Serotonin Syndrome:

  • Benzodiazepines for agitation, seizures, and muscle rigidity (first-line) 2
  • External cooling measures for hyperthermia (>104°F/40°C) 2
  • Discontinuation of all serotonergic agents 1
  • Supportive care with continuous cardiac monitoring 1
  • In severe cases, consider serotonin antagonists like cyproheptadine (under specialist guidance)

Seizures

  • Occur in approximately 1.9% of SSRI overdoses 3
  • Treat with intravenous benzodiazepines 2
  • If refractory, follow standard seizure management protocols

QTc Prolongation

  • Most significant with citalopram (68% of overdoses show QTc >440 msec) 3
  • Cardiac monitoring is essential, particularly for citalopram overdoses 3
  • Correct electrolyte abnormalities
  • Avoid other QT-prolonging medications

Prognosis

The prognosis for isolated SSRI overdose is generally excellent 4. SSRIs have a much higher safety margin in overdose compared to tricyclic antidepressants 1, 5. Most overdoses result in minor symptoms or no symptoms, especially if the amount ingested is less than 30 times the common daily dose 5.

Important Considerations

  • Co-ingestions: Most fatalities involving SSRIs have involved co-ingestion of other substances 5. Always consider and assess for other potential ingestions, particularly:

    • Monoamine oxidase inhibitors (MAOIs) - can cause severe serotonin syndrome 1
    • Other serotonergic drugs (SNRIs, tramadol, fentanyl, etc.) 4
    • Alcohol and other CNS depressants
  • Monitoring Duration: Patients should be monitored for at least 6-8 hours after ingestion, with longer observation for large ingestions or if symptoms develop

  • Citalopram Caution: Among SSRIs, citalopram poses the highest risk for cardiac complications in overdose and requires more vigilant cardiac monitoring 3

Follow-up Care

  • Psychiatric evaluation for all intentional overdoses
  • Reassessment of psychiatric medication regimen
  • Consideration of safer medication options for patients at risk of overdose
  • Secure storage of medications to prevent future overdoses

SSRIs are generally safe in overdose compared to older antidepressants, but proper management of complications, particularly serotonin syndrome, is essential for ensuring positive outcomes.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose.

Journal of toxicology. Clinical toxicology, 2004

Research

Selective serotonin reuptake inhibitor exposure.

Topics in companion animal medicine, 2013

Research

SSRI safety in overdose.

The Journal of clinical psychiatry, 1998

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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