Magnesium-Sodium Valproate Combo Could Be Beneficial for Treating Migraines


The development of a new combination drug can be a more potent and safe therapy for migraine prophylaxis.


Magnesium could enhance the anti-migraine properties of sodium valproate and reduce the required valproate dose for migraine prophylaxis, according to the results of a new study.

Despite the proven efficacy of the antiepileptic drug sodium valproate in the prevention of migraine, patients typically have poor compliance as a result of adverse effects such as fatigue, dizziness, nausea, tremor, and weight gain, researchers wrote in a recent article in The Journal of Headache and Pain.1

Meanwhile, several studies have focused on the clinical use of magnesium as a prophylactic regimen for migraine because of its high efficacy and tolerability in patients. “Oral magnesium supplementation has been reported with level B evidence for its efficacy in the prophylactic therapy of episodic migraine based on the American Academy of Neurology Guidelines,” the investigators wrote.

However, this is the first study that evaluated magnesium potency in increasing sodium valproate efficacy in combination therapy for migraine.

The investigators conducted a randomized double-blind parallel-group controlled clinical trial study on patients with migraine aged 18 to 65 years old. The patients with at least 4 monthly migraine attacks were randomly assigned to groups: sodium valproate (A), magnesium with sodium valproate (B), and magnesium alone (C).

The patients received treatment for 3 months. Investigators tracked the characteristics of migraine, including frequency, severity, duration of the attacks, and the number of painkillers monthly. The Migraine Disability Assessment (MIDAS) and Headache Impact Test-6 (HIT-6) scores were recorded at the baseline and after 3 months of treatment in each group.

“The obtained results showed that the combination of magnesium and sodium valproate had an appropriate efficacy in migraine prophylaxis, as headache severity, duration of headache, and amount of utilized painkillers were significantly lower in group B [magnesium with sodium valproate], compared to those reported for group A [sodium valproate],” the researchers wrote.

The development of a new combination drug (Magnesium Valproate) can be a more potent and safe therapy for migraine prophylaxis, the investigators concluded.

Although magnesium has been proven effective in preventing migraines in several other studies, this study indicated that valproate was “significantly more effective than magnesium in the reduction of migraine frequency and severity, duration of attacks, painkiller number, and MIDAS and HIT scores,” the investigators wrote.

Sodium valproate has been used in doses within the range of 500 to 1,000 mg/day in migraine prevention trials. In this study, a lower dose of 200/mg twice daily was prescribed with an “acceptable response,” according to the investigators.


1. Khani S, Hejazi SA, Yaghoubi M, Sharifpour E. Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial. J Headache Pain. April 7, 2021.

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