Anticonvulsant Overdose

Essentials of Diagnosis

• Drowsiness, somnolence with all

• Phenytoin: ataxia, slurred speech, nystagmus

• Carbamazepine: atrioventricular block, coma, seizures, dilated pupils, tachycardia

• Valproic acid: encephalopathy, hypernatremia, metabolic acidosis, hyperammonemia

General Considerations

• Rapid intravenous injection of phenytoin can cause acute myocardial depression and cardiac arrest owing to the solvent propylene glycol (does not occur with fosphenytoin injection)

• Phenytoin intoxication can occur with only slightly increased doses because of the small toxic-therapeutic window and zero-order kinetics

Symptoms and Signs

Phenytoin

• In overdose, often only mild symptoms even with high serum levels

• Most common manifestations

  • Ataxia

  • Nystagmus

  • Drowsiness

• Occasionally, choreoathetoid movements

Carbamazepine

• Most common manifestations

  • Drowsiness, stupor

  • Coma and seizures (with high levels)

  • Dilated pupils

  • Tachycardia

Valproic acid

• Most common manifestations

  • Encephalopathy

  • Hyperammonemia

  • Metabolic acidosis

  • Hypernatremia (from the sodium component of the salt)

  • Hypocalcemia

  • Mild liver aminotransferase elevations

  • Cerebral edema

• Hypoglycemia, as a result of hepatic metabolic dysfunction

• Coma with small pupils, can mimic opioid poisoning

Gabapentin, levetiracetam, vigabatrin, and zonisamide

• Generally cause somnolence, confusion, and dizziness

• One case report of hypotension and bradycardia after a large overdose of levetiracetam

Felbamate

• Can cause crystalluria and kidney dysfunction after overdose

• May cause idiosyncratic aplastic anemia with therapeutic use

Tiagabine, lamotrigine, topiramate

• Seizures after overdose

• Lamotrigine

  • Has sodium-channel blocking properties

  • May cause QRS prolongation and heart block

Differential Diagnosis

• Opioid intoxication

• Sedative-hypnotic overdose

Laboratory Tests

• Phenytoin toxicity

  • Levels > 20 mg/L associated with ataxia, nystagmus, drowsiness

• Carbamazepine toxicity

  • May be seen with serum levels > 20 mg/L (85 mcmol/L), though severe poisoning is usually associated with concentrations > 30–40 mg/L (127–169 mcmol/L)

  • Because of erratic and slow absorption, intoxication may progress over several hours to a day

• Valproic acid toxicity

  • Obtain frequent repeated levels to rule out delayed absorption from sustained-release formulations (eg, Depakote ER)

Medications

Activated charcoal

• For recent ingestions, give activated charcoal orally or by gastric tube

Whole-bowel irrigation

• Indicated for large ingestions of carbamazepine or valproic acid, especially of sustained-release formulations

• Administer the balanced polyethylene glycol-electrolyte solution (CoLyte, GoLYTELY) into the stomach via gastric tube at a rate of 1–2 L/h until the rectal effluent is clear

Specific treatment

• There are no specific antidotes

• Carnitine (and possibly L-arginine) may be useful in patients with valproic acid–induced hyperammonemia

• Naloxone has been reported to reverse valproic acid overdose in a few anecdotal case reports

Therapeutic Procedures

• Consider hemodialysis for massive intoxication (eg, carbamazepine levels > 60 mg/L [254 mcmol/L] or valproic acid levels > 800 mg/L [5544 mcmol/L])

When to Admit

• For phenytoin-induced ataxia if adequate home care is not available

• After symptomatic overdose of any anticonvulsant