What is the management for a risperidone (atypical antipsychotic) overdose?

Management of Risperidone Overdose

Risperidone overdose is primarily managed with supportive care, gastrointestinal decontamination when appropriate, and symptomatic treatment of extrapyramidal symptoms and cardiovascular effects, as there is no specific antidote. 1

Immediate Assessment and Stabilization

Contact a certified poison control center (1-800-222-1222) for up-to-date management guidance. 1

• Ensure adequate airway, oxygenation, and ventilation as the first priority in any overdose presentation 1
• Monitor cardiac rhythm and vital signs continuously, as cardiovascular effects including tachycardia, hypotension, and dysrhythmias can occur 1, 2
• Obtain ECG monitoring to assess for QT prolongation (typically minimal at 0-5 ms mean increase) and QRS widening, which has been reported with overdoses as low as 36-240 mg 1, 3

Gastrointestinal Decontamination

• Perform gastric lavage with normal saline if presentation is within 1-2 hours of ingestion 4
• Administer activated charcoal with sorbitol for gastrointestinal decontamination 1, 4
• Consider that paliperidone (the active metabolite) is formulated as extended-release, which may result in delayed onset of toxicity 5

Expected Clinical Manifestations

Neurological Effects

• Drowsiness and sedation are the most common findings, occurring in the majority of cases 1, 2
• Extrapyramidal symptoms (EPS) including dystonia, tremor, muscle rigidity, and akathisia can develop even at low doses, particularly in children 4, 2, 3
• Seizures have been reported, particularly with doses around 36 mg 1
• Delayed respiratory depression can occur, especially in poor metabolizers where the half-life extends to 20-30 hours (versus 3 hours in normal metabolizers) 6

Cardiovascular Effects

• Orthostatic hypotension is common and requires serial blood pressure measurements in both supine and standing positions 3, 2
• Tachycardia occurs frequently (reported in 6-7 of 31 cases in one series) 2
• QT prolongation and torsade de pointes have been reported, particularly when combined with other QT-prolonging drugs like paroxetine 1

Metabolic Abnormalities

• Hyponatremia and hypokalemia have been documented with overdoses of 240 mg 1

Specific Treatment Interventions

For Extrapyramidal Symptoms

• Administer diphenhydramine 1-2 mg/kg IV (or lorazepam 1-2 mg IV/IM for severe agitation) for dystonic reactions and EPS 4, 7, 3
• EPS typically respond immediately to anticholinergic agents, though repeat dosing may be necessary over 24-33 hours 4

For Cardiovascular Instability

• Use vasopressor agents if hypotension does not respond to IV fluids 2
• Administer antiarrhythmics only for clinically significant dysrhythmias 2

For Severe CNS Depression

• Provide endotracheal intubation and assisted ventilation for patients with coma or respiratory depression 2, 6

Laboratory Monitoring

• Complete blood count to monitor for leukocytopenia (though more relevant to chronic use) 7, 3
• Liver function tests as transaminase elevations can occur 7, 3
• Electrolytes to assess for hyponatremia and hypokalemia 1
• Standard toxicologic screen to identify coingestants 2

Clinical Course and Disposition

• Symptoms typically resolve within 24 hours in the majority of patients, with all patients asymptomatic by 72 hours post-ingestion 2
• Observe for at least 24-33 hours given the potential for delayed toxicity, especially with extended-release formulations or in poor metabolizers 4, 6, 5
• Do not discharge until orthostatic hypotension has completely resolved, as fall risk is significant 3

Critical Pitfalls to Avoid

• Do not assume rapid resolution in children, as even low doses (4 mg in a 3.5-year-old) can cause significant EPS requiring multiple doses of anticholinergic agents over 24+ hours 4
• Consider genetic polymorphism in poor metabolizers (6-8% of white patients), where half-life extends to 20-30 hours and delayed respiratory depression can occur 6
• Always assess for coingestants, particularly benzodiazepines, SSRIs, tricyclic antidepressants, and other QT-prolonging agents, as these significantly alter the clinical presentation 2, 8
• Monitor for at least 72 hours in extended-release formulations (paliperidone), as delayed onset of toxicity has been documented 5