Allopurinol as Adjunctive Therapy in Intractable Epilepsy: A Double-blind and Placebo-controlled Trial

Adenosine has been proposed to be an endogenous anticonvulsant agent. It inhibits glutamate release from excitatory neurons and neuronal firing. Therefore, adenosine agonists have potential clinical application as antiepileptics. In this double-blind randomized, placebo-controlled trial, we assessed the antiepileptic effect of allopurinol as an adjuvant agent in 38 patients with refractory epilepsy. Thirty eight patients were randomly allocated equally to allopurinol + preexisting antiepileptic (Group A) or placebo + preexisting antiepileptic (Group B) for a 6-month, double-blind, placebo-controlled study. The dose of allopurinol was titrated up to 300 mg/day (100 mg TDS). The dose of preexisting medications was maintained without change over the trial. The effect of allopurinol was evaluated by a reduction in the total number of seizures per month and duration of seizure attacks. Of 38 participants, 32 patients completed the study. There were significant differences between the two groups in terms of reduction in the total number of seizure over the trial. Seizures reduction of >30% in 66%, >50% in 55%, and >60% in 44% of cases in the allopurinol group was achieved after 2 months and persisted during the study. Nevertheless, only during month 4 was there a significant difference between the two groups regarding reduction in seizure duration. In the allopurinol group, two patients had transient rashes, two patients had mild nausea, and two experienced dizziness, but only one patient discontinued the drug due to dizziness. In the placebo group, one patient had rash and one patient had nausea. In addition, no significant hematological or hepatic changes were found during the trial in both groups. The results suggest allopurinol as a safe and effective adjuvant agent in refractory epilepsy. Based on this study, we suggest that purine metabolism pathways and the specific use of allopurinol should be further investigated with regards to neurobiology and treatment of refractory epilepsy.