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Management of Acute Anticonvulsant Overdose

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Summary

Epilepsy is the most common serious neurological condition. Overdoses with anticonvulsants are common and produce major morbidity, in many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are uncommon. Management in most cases centres on supportive measures. In general, with perhaps the exception of valproic acid (sodium valproate) and carbamazepine, the effects seen in overdose tend to be exacerbations of the adverse effects observed with lower doses of these drugs.

The drugs used to treat epilepsy are diverse and come from several classes. With acute phenytoin ingestion, the predominant effects include ataxia, lethargy and nystagmus. Cardiovascular toxicity is rare after oral ingestion and patients do not require routine cardiac monitoring.

Clinical signs and symptoms in overdoses of valproic acid are believed to be a combination of the effects of the parent drug and the metabolite 2-en-valproic acid. Prominent effects may include lethargy, coma, cerebral oedema, thrombocytopenia and metabolic acidosis. Cerebral oedema typically becomes clinically apparent 2 to 3 days after overdose, while the nadir of the haematological injury tends to be 3 to 5 days after overdose. Most patients who have taken an overdose of valproic acid will do well with gastrointestinal decontamination and aggressive supportive care only. Haemodialysis use must be weighed against its risks, but may prevent cerebral oedema, thrombocytopenia and prolonged coma.

In overdose with carbamazepine, many of the effects seen may be related to mechanisms secondary to the tricyclic structure that the drug shares with the cyclic antidepressants. The main risks are coma, seizures, depression of respiratory drive (requiring mechanical ventilation) and ventricular arrhythmias. The management of patients with carbamazepine overdose is primarily supportive. Large overdoses may require intubation and mechanical ventilation. The risks involved in haemoperfusion suggest that this procedure is warranted only in patients with ventricular dysrhythmia or unstable cardiac status that has not responded to conventional therapies.

Overdose with the succinimides is rare. The effects seen include lethargy, coma and respiratory depression. The treatment of an overdose of the succinimide derivatives is primarily supportive.

Symptoms of phenobarbital (phenobarbitone) overdose are generally exacerbations of the CNS depressant effects seen with therapeutic concentrations, i.e. slurred speech, somnolence, ataxia, obtundation and coma. With severe intoxication, hypotension and depressed cardiac output may be seen. In most cases of phenobarbital overdose, the patient will do well with gastrointestinal decontamination and aggressive supportive care only. Multiple-dose activated charcoal has been shown to reduce serum drug concentrations; however, no clear improvement in clinical effects has been shown. Haemoperfusion can restore haemodynamic stability and improve the level of consciousness. However, due to the usual successful outcome of supportive therapies, the risks involved in haemoperfusion appear warranted only in patients with unstable cardiac status that has not responded to conventional therapies.

The predominant toxic effects of benzodiazepines include sedation, ataxia, dizziness, slurred speech, confusion and ataxia. Significant effects, such as respiratory depression and death, are most likely to occur in the setting of co-ingestants or parenteral administration. The management of benzodiazepine overdose is primarily supportive. Routine flumazenil use in such patients should be avoided.

There are limited data on the effects of the newer anticonvulsants, felbamate, gabapentin and lamotrigine, in overdose. Felbamate has produced only mild effects of agitation, ataxia and somnolence after ingestion of 10 times the recommended daily dose. Overdoses of gabapentin have produced dizziness and diarrhoea, and those of lamotrigine lethargy, ataxia and nystagmus. Clinically insignificant, but mild, cardiovascular toxicity of sinus tachycardia and widened QRS interval has also been reported with lamotrigine overdose. The treatment of the newer anticonvulsants in overdose is essentially supportive after decontamination with activated charcoal.

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  1. Kentucky Regional Poison Center, 234 E. Gray Street, Medical Tower South, Suite 572, Louisville, Kentucky, 40202, USA

    Henry A. Spiller

  2. Department of Emergency Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA

    George M. Bosse

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Spiller, H.A., Bosse, G.M. Management of Acute Anticonvulsant Overdose. CNS Drugs 6, 113–129 (1996). https://doi.org/10.2165/00023210-199606020-00004

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