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Low-Dose Topiramate Plus Sodium Divalproate for Positive Responders Intolerant to Full-Dose Monotherapy


  • Conflict of Interest: None

A.V. Krymchantowski, Headache Center of Rio, Rua Siqueira Campos 43/1002, Copacabana, Rio de Janeiro, Brazil, email:


Background.— Neuromodulators such as topiramate (TPM) and divalproex sodium (DVS) are effective in the preventive treatment of migraine. Nonetheless, patients often discontinue their use due to side effects.

Objectives.— The study aims to determine whether the combination of lower doses of TPM and DVS may be useful for patients responsive to higher doses of the individual drugs but experiencing intolerable side effects.

Methods.— This clinic-based study was conducted to evaluate a series of patients who experienced at least a 50% reduction in headache frequency after 6 weeks of treatment with either TPM 100 mg/day or DVS 750 mg/day, but suffered intolerable drug-related side effects. At that point, patients were switched to TPM (50 mg in the morning and 25 mg at night) plus DVS 500 mg/day (single dose) and reevaluated after 6 further weeks.

Results.— Thirty-eight patients were evaluated. Mean age was 37 years, and 84% were female. Of the 38, 17 (77.3%) initially were using TPM only, and 10 (62.5%) initially were using DVS only. After 6 weeks on combination therapy, 27 (62.9%) reported improved tolerability without any decrease in efficacy. Five patients who initially were using TPM only and six using DVS only failed to return for follow-up or were noncompliant with treatment due to persistent or worsening side effects.

Conclusions.— This small, open-label study suggests that the combination of TPM and DVS in doses lower than those typically used for migraine prophylaxis may be an effective option for patients who benefited from higher doses of these same medications used as monotherapy but were unable to tolerate such treatment due to side effects.