Risperidone Poisoning - Management

Toxicity Profile

• Dopamine D2 receptor blockade - extrapyramidal effects
• Alpha-1 adrenoceptor antagonism - hypotension, reflex tachycardia
• IKr (hERG) antagonism - QT prolongation (modest with risperidone)
• Little-to-no muscarinic antagonism (unlike quetiapine/olanzapine) - risperidone is NOT on the antimuscarinic antipsychotic list

Clinical Features of Risperidone Overdose

Treatment - Step by Step

1. Stabilize & Supportive Care

• Assess airway, breathing, circulation - CNS/respiratory depression is the chief concern
• Position patient safely; intubate if airway reflexes impaired or GCS low
• IV access, continuous cardiac monitoring, pulse oximetry

2. Decontamination

• Activated charcoal (1 g/kg PO/NG) if within 1-2 hours of ingestion and patient is awake/airway protected
• Gastric lavage only if massive recent ingestion with secured airway
• No role for forced diuresis, hemoperfusion, or hemodialysis (risperidone is highly protein-bound)

3. Treat Hypotension

• First line: IV 0.9% NaCl bolus (normal saline preferred - the sodium load may also help any sodium channel component)
• If hypotension persists after 2 L crystalloid: norepinephrine infusion starting 0.1 mcg/kg/min, titrated to MAP ≥ 65 mmHg
• Avoid epinephrine (may worsen hypotension via beta-2 vasodilation with alpha blocked)

4. Cardiac - QT Prolongation / Torsades de Pointes

• Obtain 12-lead ECG; repeat monitoring as needed
• Correct electrolytes: K+, Mg2+, Ca2+ all shorten QT
• QTc > 500 ms or transient TdP: MgSO4 1-2 g IV (up to 4 g total for sustained TdP)
• Sustained TdP: defibrillation, overdrive pacing, or isoproterenol
• Avoid all QT-prolonging drugs
• QRS widening (rare with risperidone): treat like TCA toxicity with sodium bicarbonate 1-2 mEq/kg IV (goal pH 7.45-7.55)

5. Extrapyramidal Symptoms (EPS)

• Acute dystonia (including laryngeal dystonia - check for stridor/dyspnea):
  • Diphenhydramine 25-50 mg or benztropine 1-2 mg IV/IM/PO - response typically within 30 min
  • Refractory: lorazepam 1-2 mg IV, may repeat in 15-20 min
• Akathisia: modify antipsychotic regimen; acute: benztropine or propranolol 40-80 mg/day
• Drug-induced Parkinsonism: minimize antipsychotic dose; anticholinergic agent as above

6. Seizures

• Usually short and self-limited - may not need treatment
• Multiple seizures or status epilepticus: lorazepam 0.1 mg/kg IV (max 4 mg), repeat in 5 min if needed
• Refractory: phenobarbital 10-20 mg/kg IV or propofol infusion (requires intubation + EEG monitoring)

7. Neuroleptic Malignant Syndrome (NMS)

• NMS is not a dose-dependent overdose effect - it is an idiosyncratic reaction
• Triad: altered mental status + hyperthermia + muscle rigidity + autonomic instability
• Treatment: stop the offending drug, supportive care, benzodiazepines for rigidity/agitation, dantrolene for hyperthermia/rigidity, bromocriptine as dopaminergic agent, evaporative cooling

Monitoring & Disposition

• Symptomatic patients: admit to monitored setting
• Asymptomatic patients: observe for at least 6 hours post-ingestion (extended for paliperidone ER due to delayed absorption)
• Repeat ECGs until QTc normalized and patient asymptomatic
• Psychiatry consult for intentional overdose

Summary Table