What are the treatment and management options for a Selective Serotonin Reuptake Inhibitor (SSRI) overdose?

SSRI Overdose Management

Immediate Management

For SSRI overdose, immediately discontinue all serotonergic agents and provide aggressive supportive care with continuous cardiac monitoring, as benzodiazepines are the first-line treatment for agitation and neuromuscular symptoms, while cyproheptadine serves as a specific antidote for serotonin syndrome. 1, 2

Initial Assessment and Triage

• Any patient with suicidal intent or intentional overdose requires immediate emergency department referral regardless of dose ingested 3
• Patients experiencing symptoms beyond mild effects (anything more than vomiting, light somnolence, mydriasis, or diaphoresis) need emergency department transport 3
• Asymptomatic patients who ingested up to 5 times their therapeutic dose can be observed at home with poison center follow-up during the first 8 hours, but avoid observation during normal sleeping hours 3

Recognition of Serotonin Syndrome

• Serotonin syndrome occurs in 14-16% of SSRI overdoses and presents with the clinical triad: mental status changes, autonomic hyperactivity, and neuromuscular abnormalities 4, 5
• Clonus and hyperreflexia are highly diagnostic when occurring with serotonergic drug exposure 1
• Use Hunter Criteria for diagnosis: presence of serotonergic agent plus spontaneous clonus, inducible clonus with agitation/diaphoresis, ocular clonus with agitation/diaphoresis, tremor with hyperreflexia, or hypertonia with temperature >38°C and clonus 1
• Symptoms typically develop within 6-24 hours of ingestion 1

Treatment Algorithm

Step 1: Discontinue and Support

• Stop all serotonergic medications immediately 1, 2
• Provide IV fluids for dehydration and autonomic instability 1
• Initiate continuous cardiac monitoring, particularly for citalopram overdose which causes QTc prolongation in 68% of cases 2, 5

Step 2: Benzodiazepine Administration

• Administer benzodiazepines as first-line treatment for agitation, neuromuscular symptoms, tremor, and seizures 1, 3
• Use IV benzodiazepines for seizure control 3
• In severe refractory cases, sedation with propofol and phenobarbital may be required 6

Step 3: Temperature Management

• Implement external cooling measures (cooling blankets) for hyperthermia >40°C (>104°F) 1, 3
• Avoid antipyretics as they are ineffective - hyperthermia results from muscular hyperactivity, not hypothalamic dysregulation 1
• Never use physical restraints as they exacerbate isometric contractions, worsening hyperthermia and lactic acidosis 1

Step 4: Cyproheptadine Administration

• Administer cyproheptadine (serotonin antagonist) for serotonin syndrome: 12 mg orally initially, then 2 mg every 2 hours until symptom improvement 1, 2
• Maintenance dosing: 8 mg every 6 hours after initial control 1
• Monitor for side effects including sedation and hypotension 1

Step 5: Decontamination Considerations

• Do not induce emesis 3
• Activated charcoal is not routinely recommended for out-of-hospital management, though it can be considered since risk of SSRI-induced loss of consciousness or seizures is small 3

Critical Monitoring Parameters

• Watch for complications: rhabdomyolysis, metabolic acidosis, elevated aminotransferases, renal failure, seizures, and disseminated intravascular coagulopathy 1
• Approximately 25% of patients require intubation, mechanical ventilation, and ICU admission 1
• The mortality rate is approximately 11%, emphasizing need for prompt recognition 1
• Median length of stay is 15.3 hours, with 6.4% requiring ICU admission 5

Agent-Specific Considerations

Citalopram

• Carries highest risk for cardiac complications with QTc prolongation occurring in 68% of overdoses (5-fold higher risk than sertraline) 5
• Requires cardiac monitoring with particular attention to QT interval 2, 5

General SSRI Safety Profile

• SSRIs have low lethal potential compared to tricyclic antidepressants, making them relatively safe in overdose 4
• In one retrospective study of 313 SSRI-poisoned dogs, there were zero deaths, illustrating the relative safety profile 7
• Prognosis with treatment is excellent 7

Common Pitfalls to Avoid

• Failure to recognize serotonin syndrome early - it can progress rapidly 2
• Administering additional serotonergic medications during treatment 2
• Using physical restraints for agitation management 1
• Inadequate temperature monitoring in severe cases 2
• Confusing serotonin syndrome with neuroleptic malignant syndrome, malignant hyperthermia, anticholinergic syndrome, or withdrawal syndromes 1
• Combining SSRIs with MAOIs or other serotonergic drugs (opioids, stimulants) significantly increases risk 2