What is the recommended initial management and treatment for a patient with suspected selective serotonin reuptake inhibitor (SSRI) overdose, including airway, breathing, circulation, decontamination, monitoring, and management of serotonin syndrome, seizures, and cardiac toxicity?

SSRI Poisoning Management

For suspected SSRI overdose, immediately secure the airway and provide supportive care with continuous cardiac monitoring, while discontinuing all serotonergic agents and administering benzodiazepines as first-line treatment for agitation and neuromuscular symptoms. 1

Initial Assessment and Stabilization

Airway, Breathing, and Circulation

• Assess and secure the airway immediately, as altered mental status can progress rapidly despite SSRIs having relatively low lethal potential compared to tricyclic antidepressants 1, 2
• Provide bag-mask ventilation or rescue breathing if respiratory depression develops, maintaining oxygenation until spontaneous breathing returns 3
• Establish IV access and initiate continuous cardiac monitoring, particularly for citalopram overdose which causes QTc prolongation in 68% of cases 1
• Monitor for hypotension and cardiac arrhythmias as part of the autonomic instability spectrum 3

Risk Stratification

• Any patient with suicidal intent, intentional abuse, or suspected malicious intent requires immediate emergency department referral regardless of dose 2
• Patients experiencing symptoms beyond mild effects (vomiting, somnolence, mydriasis, diaphoresis) require emergency department transport 2
• Asymptomatic patients with unintentional ingestions up to 5 times the initial adult therapeutic dose may be observed at home with poison center follow-up during the first 8 hours 2

Gastrointestinal Decontamination

• Do not induce emesis 2
• Activated charcoal can be considered since the likelihood of SSRI-induced loss of consciousness or seizures is small, but routine out-of-hospital use cannot be advocated as there are no data suggesting specific clinical benefit 2
• Single-dose activated charcoal is the decontamination modality of choice when used, but should not be administered universally 4

Recognition of Serotonin Syndrome

Diagnostic Criteria

• Use the Hunter Criteria for diagnosis: presence of a serotonergic agent plus one of the following: spontaneous clonus, inducible clonus with agitation or diaphoresis, ocular clonus with agitation or diaphoresis, tremor and hyperreflexia, or hypertonia with temperature >38°C and ocular or inducible clonus 5, 1
• The Hunter Criteria have 84% sensitivity and 97% specificity, superior to older Sternbach criteria 6
• Clonus and hyperreflexia are highly diagnostic features when occurring with serotonergic drug exposure 5, 6, 1

Clinical Presentation

• Serotonin syndrome occurs in 14-16% of SSRI overdoses and presents with the clinical triad: mental status changes (agitated delirium, confusion), autonomic hyperactivity (hyperthermia up to 41.1°C, tachycardia, hypertension, diaphoresis, mydriasis), and neuromuscular abnormalities (myoclonus, hyperreflexia, clonus, muscle rigidity, tremor) 6, 1
• Symptoms typically develop within 6-24 hours of ingestion or dose increase 5, 1
• The mortality rate is approximately 11%, and approximately 25% of patients require intubation, mechanical ventilation, and ICU admission 5, 1

Management of Serotonin Syndrome

Step 1: Discontinue Serotonergic Agents

• Immediately discontinue all serotonergic medications as the cornerstone of treatment 5, 1
• This includes SSRIs, other antidepressants, opioids (particularly tramadol and fentanyl), and any other serotonergic agents 7

Step 2: Benzodiazepine Administration

• Administer benzodiazepines as first-line treatment for agitation, neuromuscular symptoms (tremor, hyperreflexia, clonus), and seizures 5, 1, 2
• Use intravenous benzodiazepines for seizure control in consultation with EMS medical direction 2

Step 3: Temperature Management

• Implement external cooling measures (cooling blankets) for hyperthermia >40°C (>104°F) 5, 1, 2
• Do not use antipyretics as they are ineffective—hyperthermia results from muscular hyperactivity rather than hypothalamic dysregulation 5, 1
• Never use physical restraints as they exacerbate isometric contractions, worsening hyperthermia and lactic acidosis 5, 1

Step 4: Cyproheptadine Administration (Specific Antidote)

• For moderate to severe serotonin syndrome, administer cyproheptadine: 12 mg orally initially, then 2 mg every 2 hours until symptom improvement 5, 1
• Maintenance dosing: 8 mg every 6 hours after initial symptom control 5, 1
• Pediatric dosing: 0.25 mg/kg per day 6
• Cyproheptadine functions as a serotonin antagonist at 5-HT2A receptors, directly blocking excessive serotonergic activity 6
• Monitor for side effects including sedation and hypotension 5, 1
• Continue cyproheptadine until the clinical triad resolves: mental status changes, neuromuscular hyperactivity, and autonomic instability 6
• Most mild-to-moderate cases resolve within 24-48 hours after discontinuing serotonergic agents and initiating treatment 6

Step 5: Supportive Care

• Provide IV fluids for dehydration and autonomic instability 5, 1
• Maintain continuous cardiac monitoring throughout treatment 5, 1
• Monitor for complications: rhabdomyolysis (elevated creatine kinase), metabolic acidosis, elevated aminotransferases, renal failure, seizures, and disseminated intravascular coagulopathy 5, 1

Seizure Management

• Use benzodiazepines as first-line treatment for SSRI-induced seizures 5, 1, 2
• Seizures are dose-dependent and occur more commonly with higher ingestions 7
• Standard anticonvulsant therapy should be employed if benzodiazepines are insufficient 4

Cardiac Toxicity Management

• Citalopram specifically requires close cardiac monitoring due to QTc prolongation occurring in 68% of overdoses 1
• Monitor ECG for peaked T waves, flattened T waves, prolonged PR interval, widened QRS complex, and development of arrhythmias 3
• Correct electrolyte abnormalities, particularly potassium and magnesium, as they can exacerbate cardiac toxicity 3
• For hemodynamic instability, use direct-acting sympathomimetic amines (phenylephrine, norepinephrine) rather than indirect agents like dopamine 6

Critical Monitoring Parameters

• Monitor vital signs continuously: temperature, heart rate, blood pressure, respiratory rate 6
• Assess neuromuscular status: specifically check for clonus (spontaneous, inducible, ocular), hyperreflexia, tremor, and muscle rigidity 5, 6
• Evaluate mental status: level of consciousness, agitation, confusion, delirium 6
• Laboratory monitoring: complete metabolic profile for electrolyte imbalances and liver/renal function, creatine kinase for rhabdomyolysis 1, 4

Differential Diagnosis Considerations

• Distinguish from neuroleptic malignant syndrome (NMS): NMS presents with lead-pipe rigidity, delirium, and history of antipsychotic use rather than serotonergic agents, whereas serotonin syndrome characteristically shows hyperreflexia and clonus 6
• Consider malignant hyperthermia, anticholinergic syndrome, and withdrawal syndromes in the differential 5, 1
• Exclude progressive encephalomyelitis with rigidity and myoclonus (PERM), which has a more subacute course compared to the rapid onset of serotonin syndrome 6

Common Pitfalls to Avoid

• Failure to recognize serotonin syndrome early—it can progress rapidly and has an 11% mortality rate 5, 1
• Administering additional serotonergic medications during treatment 1
• Using physical restraints for agitation management, which worsens hyperthermia 5, 1
• Inadequate temperature monitoring in severe cases 1
• Confusing mild SSRI side effects with serotonin syndrome—the difference is the clustering of signs and symptoms, their severity, and duration 8
• Failing to account for fluoxetine's exceptionally long washout period (weeks) when considering drug interactions 8

Disposition and Follow-up

• Patients with any symptoms beyond mild effects require emergency department evaluation 2
• Severe cases require ICU admission with aggressive interventions including possible intubation, mechanical ventilation, and paralysis with non-depolarizing agents (avoid succinylcholine due to risks of hyperkalemia and rhabdomyolysis) 5, 6
• Patients who respond to treatment should be observed in a healthcare setting until risk of recurrent toxicity is low and vital signs have normalized 3
• Children can experience more profound effects from small amounts of medication and warrant careful monitoring 4