What does tremors and agitation indicate in an elderly patient who has overdosed on fluoxetine (selective serotonin reuptake inhibitor)?

Serotonin Syndrome: A Life-Threatening Emergency

Tremors and agitation in an elderly patient who has overdosed on fluoxetine strongly indicate serotonin syndrome, a potentially fatal condition requiring immediate recognition and supportive care. 1

Clinical Presentation and Diagnosis

The combination of tremors and agitation represents two components of the classic serotonin syndrome triad: neuromuscular abnormalities and mental status changes. 1 According to the modified Dunkley criteria, serotonin syndrome can be diagnosed in a patient who has taken a serotonergic drug (like fluoxetine) within the last 5 weeks and presents with tremor and hyperreflexia together, or when tremor occurs with agitation or diaphoresis. 1

Key Diagnostic Features to Assess

Immediately examine for:

• Hyperreflexia and clonus (inducible or spontaneous) - these are highly diagnostic when present with serotonergic drug exposure 1
• Autonomic instability: tachycardia, hypertension, hyperthermia, diaphoresis 1
• Additional neuromuscular signs: muscle rigidity, myoclonus 1, 2
• Mental status changes: confusion, agitation, anxiety 1

The FDA drug label confirms that tremor is a documented sequela of fluoxetine overdose, along with other neurological manifestations. 3

Severity Assessment and Prognosis

This is a medical emergency with an 11% mortality rate. 1 The most common signs in non-fatal fluoxetine overdose are seizures, somnolence, nausea, tachycardia, and vomiting, but tremor specifically appears as a documented sequela. 3

Warning Signs of Severe Disease

Immediately assess for life-threatening features:

• Temperature >38°C (or >41.1°C indicating critical severity) 1
• Rhabdomyolysis with elevated creatine kinase 1
• Metabolic acidosis 1
• Renal failure with elevated creatinine 1
• Seizures 1
• ECG abnormalities including QT prolongation and ventricular arrhythmias 3

Immediate Management Algorithm

Step 1: Discontinue All Serotonergic Agents

Stop fluoxetine immediately - this is the cornerstone of treatment. 1

Step 2: Provide Supportive Care

• Benzodiazepines (e.g., lorazepam, diazepam) for agitation - this is first-line treatment 1, 4
• Ensure adequate airway, oxygenation, and ventilation 3
• IV fluids for autonomic instability and to prevent rhabdomyolysis 1
• External cooling measures for hyperthermia (cooling blankets) 1
• Continuous cardiac monitoring 1, 3

Step 3: Consider Advanced Interventions for Severe Cases

If temperature >41.1°C or severe symptoms:

• Emergency sedation, neuromuscular paralysis, and intubation 1
• ICU admission (approximately 25% of patients require mechanical ventilation) 1
• Avoid physical restraints - they worsen hyperthermia and lactic acidosis through isometric muscle contractions, increasing mortality 1

Step 4: Obtain Essential Laboratory Studies

• Complete blood count, electrolytes, BUN, creatinine 1
• Arterial blood gas (assess for metabolic acidosis) 1
• Creatine kinase (rhabdomyolysis marker) 1
• Hepatic transaminases 1
• Coagulation studies 1
• ECG 1, 3

Critical Pitfalls to Avoid

Do not confuse with other syndromes: The differential includes neuroleptic malignant syndrome, anticholinergic syndrome, malignant hyperthermia, CNS infections, and withdrawal syndromes. 1 However, clonus and hyperreflexia are highly specific for serotonin syndrome and distinguish it from these other conditions. 1

Do not induce emesis - gastric lavage with appropriate airway protection may be indicated if performed soon after ingestion, but emesis induction is contraindicated. 3

Do not rely on dialysis or forced diuresis - fluoxetine has a large volume of distribution, making these interventions ineffective. 3

Timeline and Resolution

Most cases resolve within 24 hours with appropriate supportive care and drug discontinuation. 4, 5 However, fluoxetine's very long half-life means symptoms may persist longer or have delayed onset compared to other SSRIs. 1, 6 One case report documented delayed-onset serotonin syndrome occurring 72 hours after fluoxetine overdose. 6

Special Considerations in Elderly Patients

Elderly patients are at higher risk for neurotoxicity from serotonergic agents and may have compromised renal function affecting drug clearance. 1 The combination of tremors and agitation in this population warrants aggressive monitoring and early intervention given their vulnerability to adverse outcomes.