What are the treatment and management options for a adult patient with a history of depression or anxiety who has ingested 600mg of paroxetine (Paxil), a selective serotonin reuptake inhibitor (SSRI)?

Management of 600mg Paroxetine Ingestion

For an adult who has ingested 600mg of paroxetine (30 times the standard daily dose), immediately activate emergency medical services and prepare for potential serotonin syndrome, cardiac complications, and seizures—this is a serious overdose requiring hospital-based supportive care with continuous cardiac monitoring. 1

Immediate Assessment and Stabilization

Critical Initial Actions

• Ensure adequate airway, oxygenation, and ventilation as the first priority 1
• Monitor cardiac rhythm and vital signs continuously given the risk of ventricular dysrhythmias including torsade de pointes 1
• Do NOT induce emesis—this is not recommended for paroxetine overdose 1
• Activated charcoal may be considered if presentation is within 1-2 hours of ingestion, though the FDA label does not specifically recommend forced diuresis, dialysis, hemoperfusion, or exchange transfusion as these are unlikely to be beneficial due to paroxetine's large volume of distribution 1

Expected Clinical Presentation

The most commonly reported adverse events in paroxetine overdose include 1:

• Somnolence progressing to coma
• Nausea and vomiting
• Tremor and confusion
• Tachycardia
• Dizziness

Life-Threatening Complications to Monitor

Serotonin Syndrome (14-16% of SSRI Overdoses)

This is the most critical complication to identify and treat emergently 2. Watch for the triad of symptoms that typically arise within 24-48 hours 3:

• Mental status changes: confusion, agitation, delirium 2, 3
• Neuromuscular hyperactivity: tremors, clonus, hyperreflexia, muscle rigidity 2, 3
• Autonomic hyperactivity: hypertension, tachycardia, diaphoresis, hyperthermia 2, 3

Advanced symptoms include fever, seizures, arrhythmias, and unconsciousness that can be fatal 3. Treatment requires immediate hospitalization, discontinuation of all serotonergic agents, and supportive care with continuous cardiac monitoring 3.

Cardiac Complications

Monitor for 1:

• Ventricular dysrhythmias including torsade de pointes
• Both hypertension and hypotension (paradoxically, both can occur)
• Bradycardia or tachycardia

Neurological Complications

Be prepared for 1:

• Seizures including status epilepticus
• Mydriasis
• Dystonia and myoclonus
• Stupor progressing to coma

Other Serious Complications

Watch for signs of 1:

• Hepatic dysfunction (hepatic failure, hepatic necrosis, jaundice, hepatitis, hepatic steatosis)
• Rhabdomyolysis
• Acute renal failure
• Urinary retention
• Manic reactions
• Aggressive reactions and syncope

Hospital Management Protocol

Supportive Care Framework

No specific antidote exists for paroxetine overdose 1. Management consists of:

• General supportive measures employed for any antidepressant overdose 1
• Continuous cardiac monitoring for dysrhythmias 1
• Serial neurological assessments for seizure activity and mental status changes 1
• Fluid management and electrolyte monitoring 1

Duration of Observation

Given paroxetine's elimination half-life of approximately 21-24 hours 4, 5, and the potential for delayed onset of serious complications, patients require extended observation of at least 24-48 hours with continuous monitoring 3.

Critical Pitfalls to Avoid

Polypharmacy Considerations

Always consider the possibility of multiple drug involvement 1. This is particularly important because:

• If the patient is also taking tricyclic antidepressants, paroxetine's inhibition of CYP2D6 may cause accumulation of the tricyclic and extend the time needed for medical observation 1
• Combining paroxetine with other serotonergic medications dramatically increases serotonin syndrome risk 2, 3

Underestimating Severity

The largest documented survival involved 2,000mg of paroxetine 1, but 600mg represents a serious overdose (30 times the maximum recommended daily dose) that can be fatal 1. Of 342 reported overdose cases worldwide, 48 were fatal, with 17 appearing to involve paroxetine alone 1.

Premature Discharge

Even if the patient appears stable initially, serious complications can develop over 24-48 hours, particularly serotonin syndrome 3. Do not discharge based on initial presentation alone.

Psychiatric Evaluation

Once medically stabilized, mandatory psychiatric evaluation is required given this represents either a suicide attempt or accidental ingestion in a patient with depression/anxiety 1. The patient should not be discharged until psychiatric clearance is obtained and appropriate follow-up is arranged.