Preventing Migraines With Valproic Acid

An Anti-Seizure Medication May Do the Trick for Some People

Show Article Table of Contents

Valproic Acid for Migraine Prevention

Garo/Phanie/Getty Images


The American Academy of Neurology and American Headache Society support the use of valproic acid for preventing migraines.

It's unclear exactly how this anti-seizure medication works to squelch migraine attacks, but it likely has something to do with the neurotransmitter GABA (Gamma-aminobutyric acid). Experts believe that by blocking the enzyme that normally breaks GABA down, valproic acid essentially increases brain GABA levels.

As an inhibitory neurotransmitter, GABA then reduces the nerve cell excitability/firing that normally propagates a migraine attack.


Valproic acid, known by the brand name Depakene in the United States, is approved by the Food and Drug Administration (FDA) for treating seizures and preventing migraines. It is also used off-label to treat painful diabetic nerve pain and post-herpetic neuralgia, among other conditions.

In terms of dosing valproic acid, doctors usually begin at a low dose, around 250 milligrams (mg) per day, and then depending on the response and how well the person tolerates the drug, the dose may be increased up to a maximum of 1,500 mg per day.

Overall, research suggests that a higher dose (1500 mg/day) increases a person's chance of reducing the number of migraine attacks they experience (the goal being to reduce the number of migraine attacks by more than 50 percent).

In addition, a higher dose increases the likelihood of reducing particularly debilitating migraines—ones associated with nausea, vomiting, phonophobia (sound sensitivity) or photophobia (light sensitivity).

Adverse Effects

It's important to discuss the adverse effects you may experience while taking valproic acid with your doctor.

Some of these potential adverse effects include:

  • Nausea
  • Sleepiness
  • Tremor
  • Dizziness
  • Upset stomach
  • Weight gain
  • Hair loss


Valproic acid is a pregnancy category X drug, meaning this drug is absolutely contraindicated during pregnancy, as the risk clearly outweighs any potential benefit. Not only has valproic acid been linked to birth defects (especially neural tube defects, like spina bifida), but it has also been linked to lower intelligence quotient (IQ) scores in children whose mothers took valproic acid during pregnancy.

Due to these high risks, the FDA advises that valproic acid not be taken by women of childbearing age for preventing migraines.

Besides pregnancy, valproic acid cannot be taken by people with the following health conditions:

  • Liver disease
  • An allergy to valproic acid
  • Urea cycle disorder (for example, ornithine transcarbamylase deficiency—a rare genetic disease)


If you are taking valproic acid, be aware there are serious warnings associated with taking it, such as a risk for liver failure, life-threatening pancreatitis, suicidal thoughts and behavior, significant sleepiness (especially in the elderly), hypothermia, decreased platelets (called thrombocytopenia), multi-organ hypersensitivity reaction, and hyperammonemic encephalopathy.

It's important to be knowledgeable of the symptoms of these conditions. Below are a few examples:

  • Pancreatitis: abdominal pain, nausea, vomiting, and/or a loss of appetite
  • Thrombocytopenia: easy bruising
  • Multi-organ hypersensitivity reaction: Fever along with swollen lymph nodes and/or rash
  • Hyperammonemic encephalopathy: Thinking and memory problems with vomiting and excessive sleepiness


Valproic acid may interact with certain drugs, such as aspirin, the antidepressants Elavil (amitriptyline) and Pamelor (nortriptyline), the carbapenem class of antibiotics, other medications for seizures, and coumadin (warfarin).

To prevent any drug interaction and/or so your healthcare provider knows to monitor you more closely, be sure to inform them of all the medications you are taking, both prescription and over-the-counter ones. On your medication list, remember to include supplements, herbals, and vitamins as well.

Lastly, since valproic acid may cause drowsiness, be sure to let your healthcare provider know if you consume alcohol or are taking medications that make you sleepy, such as narcotic pain medication, cold or allergy drugs, or sleep aids.

A Word From Verywell

Keep in mind, while valproic acid may be an option for migraine prevention in some people, it's not a sensible option for everyone, especially women in their childbearing years (a population that unfortunately tends to bear the brunt of migraines).

That said, there are many other migraine prevention drug options out there, such as the high blood pressure medications propranolol and metoprolol, the anti-seizure medication Topamax (topiramate), and the antidepressants Elavil (amitriptyline) and Effexor (venlafaxine). If you do not respond to these more conventional migraine preventive drugs, your doctor may consider the once-a-month injectable medication, Aimovig (erenumab).

Was this page helpful?
Article Sources
  • Bajwa ZH, Smith JH. (2018). Preventive treatment of migraine in adults. In: UpToDate, Swanson, JW (Ed), UpToDate, Waltham, MA.
  • FDA Drug Safety Communication (2013). Valproate anti-seizure products contraindicated for migraine prevention in pregnant women due to decreased IQ scores in exposed children. doi: 10.1002/14651858.CD010611
  • Linde M, Mulleners WM, Chronicle EP McCrory DC. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev. 2013 Jun 24;(6):CD010611. doi: 10.1002/14651858.CD010611
  • Shamliyan TA et al. Preventive Pharmacologic Treatments for Episodic Migraine in Adults. J Gen Intern Med. 2013 Sep;28(9):1225-37.
  • Silberstein SD. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention in adults: report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Headache Society. Neurology. 2012 Apr 24;78(17):1337-45. doi: 10.1212/WNL.0b013e3182535d20