Alcohol has been known to produce seizures since antiquity, but the relationship is complex. Seizures27 and status epilepticus87 have been reported in both acute intoxication and withdrawal. They also may be secondary to complications of alcohol abuse, such as subdural or parenchymal hemorrhage, stroke, or head trauma.27,88,89

Alcohol acts as a depressant at both GABAA-benzodiazepine receptor complexes and at N-methyl-D-aspartate (NMDA)–glutamate receptors. It down-regulates calcium channels and disrupts the neurotransmitter receptors embedded in myelin, with chronic use.89 Other theories of withdrawal seizures include zinc deficiency90 and lowering of the ratio of aromatic to branched-chain amino acids.91

Withdrawal seizures generally occur 24 to 72 hours after last intake and precede delirium tremens in 5% of untreated cases.88 Studies that used phenobarbital loading were most successful in avoiding recurrent seizures and delirium tremens in one emergency room series.29 A kindling model in animals has documented spontaneous seizures after several alcohol withdrawals.89

Moderate amounts of alcohol can bring out epileptiform discharges on epilepsy patients' EEGs without affecting their seizure threshold, but recent reviews note an association of seizures with alcohol intoxication.92 These patients may or may not have structural lesions, such as prior head trauma or stroke.27,88,89 Although cessation of alcohol use is the best prevention of these seizures, some patients do need anticonvulsants.

Many people with epilepsy have the misconception that they cannot use any antiepileptic drug (AED) while drinking (probably because prescription bottles are so labeled), and therefore those who require long-term medication add the risk of medication withdrawal to alcohol intake when they drink.88 Physicians are often afraid to give alcoholics phenobarbital (fearing respiratory problems from the combined central nervous system depressant effect)89 or valproic acid (because of potential liver and pancreas toxicity), so phenytoin is prescribed instead. Phenytoin has the highest incidence of seizures with noncompliance, whether deliberate or accidental.88

Although pure withdrawal seizures should not be treated with AEDs, most alcoholics have symptomatic and withdrawal seizures. By emphasizing improved compliance, including the importance of not running out of medication and not deliberately stopping AEDs while drinking, alcoholic patients with seizure disorders can be successfully treated. The safest AEDs for alcoholic patients who may be poorly compliant are those with a prolonged anticonvulsant effect despite a short half-life, such as sodium valproate,28 or those with long half-life, such as phenobarbital.29 Magnesium deficiency should be treated as well.27,88

When the relationship between their seizures and drinking is pointed out, some patients are sufficiently frightened that they voluntarily enter detoxification programs.27–29

Adapted from: Koppel BS. Contribution of drugs and drug interactions (prescribed, over the counter, and illicit) to seizures and epilepsy. In: Ettinger AB and Devinsky O, eds. Managing epilepsy and co-existing disorders. Boston: Butterworth-Heinemann; 2002;155–173. With permission from Elsevier (www.elsevier.com).

Authored By: 
Barbara S. Koppel MD
I<
Reviewed By: 
Steven C. Schachter MD
on: 
Monday, March 1, 2004