Risperidone toxicity

Risperidone is an atypical antipsychotic agent associated with tachycardia and acute dystonic reactions.

Toxic Mechanism:

Risperidone antagonises the mesolimbic dopamine (D2), serotonin and alpha 1 + 2 receptors. Compared with other antipsychotics it has a low affinity for histamine the muscarninic receptors, meaning less CNS depression and anticholinergic features.

Toxicokinetics: 

• Rapidly absorbed
• Moderate volume of distribution 1.5 L/kg
• Highly protein bound
• Metabolised in the liver and excreted in the urine

Resuscitation:

• Rarely required

Risk Assessment

• Dose related risk assessment is poorly defined
• Children: >1 mg is associated with clinical features. Acute dystonic reactions are more common in children.
• Clinical features should manifest within 4 hours and resolve by 24 hours
  • Sinus tachycardia 50%
  • Acute dystonia 10%
  • Mild sedation
  • QT prolongation but no reports of Torsades de pointes
  • CNS depression is rare

Supportive Care

• General supportive care

Investigations

• Screening: 12 lead ECG, BSL, Paracetamol level
• Specific:
  • ECG at presentation and 4 hours (if normal no further ECGs required)
  • Sinus tachycardia is common
  • Reports of minor QT prolongation but no Torsades de pointes.

Decontamination:

• Not routinely indicated

Enhanced Elimination

• Not clinical useful

Antidote

• Benztropine for acute dystonic reactions.
  • Over 3 yrs 0.02 mg/kg IM or IV.
  • Adults 1mg.
  • May repeat in 15 minutes.

Disposition

• Children who are symptomatic all need review
• Patients who are well with a normal baseline ECG can be medically cleared at 4 hours post ingestions
• Symptomatic patients need supportive care until toxicity resolves
• Patients should be warned that extrapyramidal movements may occur up to 3 days later.

References:

• Burns MJ. The pharmacology and toxicology of atypical antipsychotic agents. Journal of Toxicology-Clinical Toxicology 2001; 39(1): 1-14.
• Cobaugh DJ et al. Atypical antipsychotic medication poisoning an evidence based consensus guideline for out-of-hospital management. Clinical Toxicology 2007; 45(8):918-942
• Page CB, Calver LA, Isbister GK. Risperidone overdose causes extrapyramidal effects but not cardiac toxicity. Journal of Clinical Psychopharmacology 2010; 30:387-390
• Tan HH, Hoppe J, Heard K.  A systematic review of cardiovascular effects after atypical antipsychotic medication overdose.  American Journal of Emergency Medicine 2009; 27:607-616.