Antipsychotic toxicity

Background

• Isolated overdose of antipsychotics is rarely fatal
• Toxicity results in blockade of some or all of the following receptors:
  • Dopamine - extrapyramidal symptoms
  • Alpha-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
  • Sinus tachycardia
  • QT prolongation

Differential Diagnosis

Anticholinergic toxicity

• Medications
  • Atropine
    • Lomotil toxicity
  • Antihistamines
  • Antidepressants
    • Tricyclic antidepressant (TCA) toxicity
    • SSRIs
  • Antipsychotics
  • Muscle relaxants
  • Anti-Parkinsonians
• Plants
  • Jimson weed (Devil's trumpet)
  • Amanita mushroom

Evaluation

Workup

• 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)

Management

Supportive

• Hypotension
  • IVF
  • Norepinephrine
• QT prolongation
  • Treat all with QTc >500ms with magnesium 2-4gm IV over 10min

Extrapyramidal

• Diphenhydramine 25-50mg IV/IM OR benztropine 1-2mg IV/IM
• Oral therapy with either of above meds should be continued for 2 weeks

Disposition

• 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

• Neuroleptic Malignant Syndrome (NMS)
• Tardive dyskinesia
• Beta-Blocker Toxicity
• Calcium Channel Blocker Toxicity
• Extrapyramidal reaction

External Links

• DDxOf: Atypical Antipsychotic Overdose

References

Authors

Jordan Swartz, Tom Fadial, Ross Donaldson, Claire, Aaron Fields, Michael O'Brien, MD, Neil Young, Daniel Ostermayer