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Valproic Acid

In the pediatric patient diagnosed with refractory migraine, is valproic acid an effective treatment?


Plain language summary from the office of evidence based practice 

Migraine in the ED Team recommendations: The Migraine in the ED Team makes a conditional recommendation to use valproic acid as a second line treatment option for children who present to the ED with a refractory migraine headache. Valproic acid is the treatment of choice if NSAIDs have been administered (ibuprofen < 6 hours from prior administration or naproxen sodium < 12 hours from prior administration). Assure pregnancy test is negative before administering valproic acid. Alternative approaches may be equally reasonable. Four randomized control trials are included in this review. The included studies are methodologically strong, but the evidence is downgraded for imprecision, due to the small number of subjects with the desired outcomes.

Literature synthesis: Valproic acid was compared to other medications on the outcome- pain free in less than two hours. There was no significant difference between subjects treated with valproic acid and ketorolac (Friedman et al., 2014) or dihydroergotamine (Edwards, Norton, & Behnke, 2001).

Valproic acid was compared to other medications on the outcome- need for rescue medications. Subjects treated with valproic acid required significantly more rescue medications than subjects treated with metoclopramide or ketorolac (Friedman et al., 2014), or prochlorperazine (Tanen, Miller, French, & Riffenburgh, 2003).

Valproic acid was compared to other medication in the outcome- adverse events. Adverse events were not significantly different than metoclopramide, ketorolac, or dihydroergotamine (Edwards et al., 2001, Friedman et al., 2014). There were significantly less adverse events when valproic acid was compared to sumatriptan (Rahimdel, Mellat, Zeinali, Jafari & Ayatollahi, 2014).

The dose of valproic acid is 20 mG/kg with a maximum of 1 gram to be administered over one hour.

See Appendix C for the full Critically Appraised Topic (CAT).



These guidelines do not establish a standard of care to be followed in every case. It is recognized that each case is different and those individuals involved in providing health care are expected to use their judgment in determining what is in the best interests of the patient based on the circumstances existing at the time. It is impossible to anticipate all possible situations that may exist and to prepare guidelines for each. Accordingly these guidelines should guide care with the understanding that departures from them may be required at times.