Antipsychotic toxicity

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  • Isolated overdose of antipsychotics is rarely fatal
  • Toxicity results in blockade of some or all of the following receptors:
    • Dopamine - extrapyramidal symptoms
    • α-1 - orthostatic hypotension, reflex tachycardia
    • Muscarinic - anticholinergic symptoms
    • Histamine - sedation

Clinical Features

Evaluation of SGA (Second Generation Antipsychotic) Toxicity
  • Extrapyramidal
    • Acute dystonic reaction
      • Tongue protrusion, facial grimacing, trismus, oculogyric crisis
    • Akathisia
  • CNS
    • Lethargy, ataxia, dyarthria, confusion, coma
    • Seizure (1%)
  • Anticholinergic Effects
    • Tachycardia, dry mucous membranes, dry skin, decreased bowel sounds, delirium
  • ECG changes

Differential Diagnosis

Anticholinergic toxicity Causes



  • POC Glucose
  • ECG (QT interval)
  • Co-ingestions: serum acetaminophen, salicylate, EtOH level, other known drug levels
  • Urine toxicology screen
  • Chemistry (metabolic acidosis, electrolytes, renal function)
  • LFT (hepatotoxicity)
  • CK (rhabdomyolysis)
  • Serum osmolarity (osmolar gap)
  • ABG (carboxyhemoglobin, methemoglobin)





  • Consider discharge after 6hr as long as there are all of the following:
    • No mental status changes
    • Normal HR/BP
    • No orthostatic hypotension
    • Normal QT interval

See Also

External Links


  1. Dawson AH, Buckley NA. Pharmacological management of anticholinergic delirium – theory, evidence and practice. Br J Clin Pharmacol. 2015;81(3):516-24.