Retrospective Chart Review of Intravenous Valproate Sodium as a Preventive Treatment for Patients With Chronic Migraine

Nina Riggins, Annika Ehrlich, Henna Sawhney, Laura Dapkus, Morris Levin
Headache 2020, 60 (3): 617-620

OBJECTIVE: This is a small pilot study to evaluate the effectiveness of an intravenous (IV) valproate sodium therapy protocol for migraine prevention in a population of patients with chronic migraine refractory to multiple preventive medications.

BACKGROUND: Valproate sodium is an anti-epileptic and mood stabilizer that has been shown to prevent migraine when used daily in oral form. The specific mechanism of action in migraine is unknown, but it may be related to suppressing inflammation and increasing brain Gamma-aminobutyric acid levels. It also may relate to its ability to suppress cortical spreading depression. Multiple studies have suggested that valproic acid and its derivatives may inhibit Calcitonin gene-related peptide. In the present work, we undertook a small pilot study to evaluate the effectiveness of an IV valproate sodium therapy for migraine prevention in a population of patients with chronic migraine refractory to multiple preventive medications.

METHODS: Fourteen adult patients with chronic migraine were admitted for a 4-day course of IV valproate sodium. Patients received 250 mg of valproate sodium over a standard infusion time of 60 minutes every 8 hours. Most patients received 9 doses over the 4-day course of treatment. One patient had to discontinue after 1 dose of 250-mg valproate sodium, as this patient experienced an increase in his previous symptoms of nausea, vomiting, and vertigo with his first dose. To avoid positive selection bias, we evaluated the first admission for valproate IV therapy in patients with multiple admissions; there was 1 patient with 2 admissions and 1 with 3 admissions for IV valproate sodium. Of note - all admission outcomes for these patients were similar. Headache diaries were reviewed from 1 month before, during, and approximately 2 months after their admission.

STATISTICAL ANALYSES: Due to the observational nature of the study and small sample size, we did not think that quantitative statistical analysis would add more meaning to this pilot study. Formal quantitative statistical analysis was not performed in this study and descriptive statistical analysis was used due to this being a pilot proof of concept study. Physician clinical judgment in combination with patient reports were used to assign a dichotomous conclusion on clinical improvement for each patient. In the future, we plan to create a larger study, including additional treatment groups for control, such as IV Dihydroergotamine or IV Chlorpromazine, in order to quantify improvement of symptoms.

RESULTS: A total of 9 out of 13 (69%) patients had an improvement in their headache post-admission and reported a reduction in headache frequency, intensity, and/or use of acute medications 4-6 weeks following their admissions. A total of 5 out of 13 (38%) patients also reported an improvement in headache intensity during the 4-day period of inpatient admission. The other 8 out of 13 (62%) patients reported stable headache pattern. One patient had feelings of restlessness, which improved with prolongation of infusion time to 120 minutes.

CONCLUSION: These results indicate that this repetitive dosing valproate sodium protocol is a safe and well-tolerated intervention for the treatment of chronic migraine resistant to oral medications. Given the promising outcomes on patient headache improvement with this small pilot study, studies to confirm this benefit in a larger cohort of chronic migraine patients are warranted, preferable with the addition of a blinded control group for comparison.

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