Migraine cannot be cured and the aim, shared with the patient, is to minimise the impact of the illness on the patient's life and lifestyle. The aim of prophylaxis is to reduce the number of migraine attacks. Prophylaxis should be considered when appropriately used acute management gives inadequate control of symptoms. The efficacy and safety of topiramate 50 mg/d and thioctic acid (α-lipoic acid) 300 mg/d either as monotherapy or in combination were investigated as migraine prophylactic agents. Forty secondary school migraineur girls were enrolled in the study. The study was conducted in two phases, a prospective baseline phase and 1-month treatment phase. Combined topiramate/thioctic acid therapy was more effective than either topiramate or thioctic acid monotherapy as a migraine-preventive treatment. Combined topiramate/thioctic acid therapy decreased the mean monthly migraine frequency from 5.86 ± 1.2 to 2.6 ± 0.98 (p ⩽ 0.05), topiramate (50 mg/d) from 5.71 ± 1.4 to 4.75 ± 1.5 and thioctic acid (300 mg/d) from 5.68 ± 1.6 to 5.22 ± 1.8. Reduction in mean monthly migraine days was also significantly greater in the group receiving combined topiramate/thioctic acid (from 12.32 ± 1.85 to 5.74 ± 1.1) compared to those receiving either topiramate 50 mg/d (from 12.7 ± 1.34 to 11.85 ± 1.35) or thioctic acid 300 mg/d (from 12.5 ± 1.72 to 11.65 ± 1.44). The responder rate (% of patients showing ⩾50% reduction in monthly migraine frequency) was 85% in patients receiving combined topiramate/thioctic acid therapy compared to 30% and 20% in patients receiving either topiramate or thioctic acid, respectively. The incidence of adverse events was higher in patients receiving topiramate (50 mg/d) monotherapy. The most common adverse events were nausea, fatigue, paraesthesia and taste perversion. We conclude that combined topiramate/thioctic acid therapy is more effective and better tolerated than topiramate monotherapy. The combination has lower monthly medication costs compared to the traditionally used topiramate 100 mg monotherapy.