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Lorazepam Prevents Recurrence of Alcohol-Related Seizures



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Am Fam Physician. 1999 Jul 1;60(1):278-280.

Alcohol abuse has been linked to seizures in adults, although the reason for this is not well established. Theories that may explain the link include a seizure-inducing effect of alcohol, an exacerbation of preexisting epilepsy or the presence of structural abnormalities in the brain related to chronic alcohol intake. Phenytoin is not effective in preventing the recurrence of these seizures, but benzodiazepines have been shown to be effective in the management of acute alcohol syndromes, including the primary prevention of seizures. D'Onofrio and colleagues conducted a randomized, double-blind trial to evaluate the use of lorazepam to prevent recurrent alcohol-related seizures in patients who initially present with a seizure.

Patients enrolled in the trial were adults with a known history of alcohol abuse. They presented to one of two urban emergency departments after having a witnessed generalized seizure and had consumed one or more drinks in the previous 72 hours. An alcohol-related seizure was diagnosed on the basis of a history of alcohol use, no history of recent trauma and review of the patient's medical record. Patients were excluded from the trial if they were found to have another possible cause for the seizures, including hyponatremia, hypoglycemia, hypocalcemia or hypomagnesemia. Patients who were found to have used cocaine or phenobarbital were also excluded because of the anticonvulsant effect of these agents. Patients had computed tomographic scans of the head and an electroencephalogram, if clinically indicated.

Patients who were eligible to participate in the trial were randomly assigned to receive either 2 mg of lorazepam in 2 mL of saline or 4 mL of saline intravenously. The patients and all care providers were unaware of the treatment assignments. In addition, all patients were given fluids, 100 mg of thiamine, 2 g of magnesium and 1 ampule of intravenous multivitamins. The observation period ended if a second seizure occurred in the emergency department or six hours after lorazepam or placebo was administered.

Initially, 229 patients were enrolled, 43 of whom were excluded on the basis of established criteria. Almost all of the patients were men, and the average age was 45 years in the lorazepam group and 44 years in the placebo group. Researchers found that 85 percent of the patients drank at least one pint of distilled alcohol per day for more than 10 years and that 90 percent had the first seizure seven to 48 hours after their last drink. One hundred patients received lorazepam and 86 patients were given placebo.

Twenty-four percent of patients in the placebo group had a second seizure compared with 3 percent in the lorazepam group. When additional patients were excluded after enrollment, the percentages remained essentially the same—27 percent of the patients taking placebo had a second seizure compared with 3 percent of patients taking lorazepam. Thirty-six patients in the placebo group and 29 patients in the lorazepam group were admitted to the hospital. Researchers were able to determine readmission to the emergency department (within 48 hours after discharge) with a seizure by reviewing ambulance records. Seven patients from the placebo group and one patient from the lorazepam group were readmitted, although in the case of the latter patient, it happened only 2.5 hours after discharge.

The authors conclude that lorazepam is safe and effective in preventing recurrent alcohol-related seizures. It may also decrease the number of hospitalizations after a second observed alcohol-related seizure. This is significant, as many hospitals require admission of a patient who has had a second seizure. The study also used logistic-regression analysis to determine if there were any independent predictors for recurrent seizures. The authors found no statistically significant association with age, sex, serum ethanol level, number of years of alcohol use or time since the last drink.

D'Onofrio G, et al. Lorazepam for the prevention of recurrent seizures related to alcohol. N Engl J Med. March 25, 1999;340:915–9.


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