Background: Approximately 5-10% of epileptic patients do not respond to antiepileptic drugs. Adenosine has an inhibitory effect on the nervous system and its metabolism is prevented as a side effect of allopurinol, a xanthine oxidase inhibitor. The current study evaluates the efficacy of allopurinol in intractable epilepsy.

Methods: In this double-blind case-control clinical trial, of the 38 epileptics with intractable seizures, 18 received 300 mg allopurinol daily and 20 received a placebo as adjuvant treatment to their previous antiepileptic drugs. The patients were first examined two weeks after initiation of the treatment and then monthly for a total of six months, during which they were evaluated for seizure control and possible side effects.

Result: Of the 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizures over the entire six-month trial. A seizure reduction of 30% observed in 66% of the patients, 50% in 55%, and 60% in 44% of the cases in the allopurinol group was achieved after two months and persisted throughout the study. Furthermore, a significant difference in seizure duration was found between the two groups in month four of the trial. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness; however, only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one had nausea. In addition, no significant hematological or hepatic changes were found during the trial in either group.

Conclusions: The results suggest that allopurinol is a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolic pathways and the specific use of allopurinol should be further investigated for the treatment of refractory epilepsy.