What are the symptoms, signs, and immediate management recommendations for a quetiapine overdose?

Quetiapine Overdose: Clinical Presentation and Management

Signs and Symptoms

Quetiapine overdose primarily causes CNS depression, cardiovascular effects, and respiratory compromise, with drowsiness being the most common presentation (76% of cases), followed by tachycardia (56%), and potentially progressing to coma (10%), hypotension (18%), and respiratory depression (5%). 1, 2

Central Nervous System Effects

• Drowsiness and sedation are the hallmark features, occurring in approximately three-quarters of patients 2
• Coma develops in 10% of cases, with loss of consciousness typically occurring 1.5-2.5 hours post-ingestion 2, 3
• Seizures occur in approximately 2% of overdoses 2, 4
• Delirium may develop in some patients 4

Cardiovascular Manifestations

• Sinus tachycardia is present in 56% of cases and may persist for 40+ hours 2, 3
• Hypotension occurs in 18% of patients, with quetiapine having twice the risk compared to other antipsychotics (OR 2.05) 2
• QT prolongation has been reported in post-marketing surveillance, though the clinical significance is unclear as it may represent overcorrection due to tachycardia 1, 4
• Ventricular arrhythmias are rare, with only isolated reports of ventricular tachycardia and no documented torsades de pointes in large case series 2
• First-degree heart block and hypokalemia have been reported in massive overdoses 1

Respiratory Effects

• Respiratory depression requiring ventilatory support occurs in 5% of cases 2
• Need for intubation is nearly twice as likely compared to other antipsychotic overdoses (OR 1.92) 2

Metabolic Disturbances

• Hyperglycemia may occur 5
• Transient hypothyroidism has been reported in extreme overdoses 5

Immediate Management Priorities

Establish and maintain airway patency immediately, as obtundation and respiratory depression are the primary life-threatening complications. 1

Airway and Breathing

• Secure the airway and ensure adequate oxygenation and ventilation as the first priority 1
• Consider early intubation if the patient is unconscious or has compromised airway reflexes, as the risk of aspiration is significant due to potential obtundation, seizures, or dystonic reactions 1
• Provide mechanical ventilation if respiratory depression develops 2

Gastrointestinal Decontamination

• Perform gastric lavage after intubation if the patient is unconscious 1
• Administer activated charcoal together with a laxative 1
• Avoid induced emesis due to the risk of aspiration from obtundation, seizures, or dystonic reactions 1

Cardiovascular Monitoring

• Initiate continuous ECG monitoring immediately to detect possible arrhythmias 1
• Treat hypotension with intravenous fluids and/or sympathomimetic agents 1
• Avoid epinephrine and dopamine, as beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha blockade; use alternative vasopressors 1

Antiarrhythmic Considerations

• Avoid disopyramide, procainamide, and quinidine if antiarrhythmic therapy is needed, as these carry theoretical hazard of additive QT-prolonging effects 1
• Avoid bretylium, as its alpha-adrenergic-blocking properties may be additive to quetiapine, resulting in problematic hypotension 1

Neurological Management

• Administer anticholinergic medication only in cases of severe extrapyramidal symptoms 1
• Manage seizures with standard anticonvulsant therapy if they occur 2

Risk Stratification

High-Risk Features Requiring ICU Admission

• Reported dose ≥3 grams is significantly associated with ICU admission and length of stay >24 hours 4
• Glasgow Coma Scale <15 at 4+ hours post-ingestion 4
• Presence of coma, respiratory depression, or hypotension 2
• Pre-existing severe cardiovascular disease increases risk of overdose complications 1

Lower-Risk Profile

• **Reported dose <3 grams** AND **Glasgow Coma Scale score of 15** at least 4 hours post-ingestion, with no coingestants, predicts patients not requiring ICU admission or length of stay >24 hours 4

Ongoing Management

Supportive Care

• No specific antidote exists for quetiapine; treatment is entirely supportive 1
• Consider multiple drug involvement in all cases 1
• Continue close medical supervision and monitoring until the patient fully recovers 1

Observation Period

• Median length of stay is approximately 35 hours for quetiapine overdoses 4
• Monitor for delayed effects, as symptoms may progress over the first 2.5 hours post-ingestion 3
• Persistent tachycardia may last up to 40 hours and requires continued cardiac monitoring 3

Prognostic Indicators

Mortality Risk

• Death has been reported in clinical trials following overdoses as low as 13.6 grams when quetiapine was ingested alone 1
• Three deaths occurred in a series of 945 cases, all involving coma, tachycardia, and respiratory depression requiring ventilatory support 2
• Major medical outcomes or death are 2.6 times more likely with quetiapine compared to other antipsychotics (OR 2.62) 2

Dose-Response Relationship

• Reported ingested dose correlates highly with peak drug concentration (r²=0.84), confirming that patient history is reliable 4
• Extreme overdoses (up to 36 grams) have been survived with aggressive supportive care 5
• Survival has been reported in acute overdoses up to 30 grams 1

Common Pitfalls to Avoid

• Do not use epinephrine or dopamine for hypotension, as they may worsen blood pressure through beta-stimulation in the presence of alpha-blockade 1
• Do not delay airway protection while attempting other interventions, as respiratory depression can progress rapidly 1
• Do not assume cardiac safety based on normal QT interval alone; monitor for at least 40 hours due to persistent tachycardia 3
• Do not discharge patients early even if initially alert, as deterioration can occur 2-3 hours post-ingestion 3