Does valproate (valproic acid) cause severe headaches?

From the Guidelines

Valproate can cause headaches as a side effect, though severe headaches are less common. Valproate, also known as valproic acid or by brand names like Depakote or Epilim, is an anticonvulsant medication used to treat epilepsy, bipolar disorder, and migraines. Headaches may occur particularly when starting treatment or after dose increases. If you experience severe headaches while taking valproate, you should contact your healthcare provider promptly as this could potentially indicate a serious reaction. Other concerning symptoms that warrant immediate medical attention include unusual bleeding or bruising, yellowing of the skin or eyes, severe nausea or vomiting, or significant drowsiness. Your doctor might need to adjust your dosage or switch you to an alternative medication if headaches are persistent or severe. Never stop taking valproate suddenly without medical supervision, as this can trigger seizures in people with epilepsy or worsen other conditions being treated.

Key Points to Consider

• Valproate is used to treat various conditions, including epilepsy, bipolar disorder, and migraines 1.
• It can cause headaches, but severe headaches are less common 1.
• If severe headaches occur, it is essential to contact a healthcare provider promptly to rule out any serious reactions 1.
• Other symptoms that require immediate medical attention include unusual bleeding, yellowing of the skin or eyes, severe nausea or vomiting, and significant drowsiness 1.
• Dosage adjustments or alternative medications may be necessary if headaches are persistent or severe 1.

Management and Prevention

• Educating patients about the control of acute attacks and preventive therapy is crucial 1.
• Recommended first-line agents for the prevention of migraine headache include propranolol, timolol, amitriptyline, divalproex sodium, and sodium valproate 1.
• Medications with proven efficacy but limited published data on adverse events or frequent or severe adverse events include flunarizine, lisuride, pizotifen, time-released DHE, and methysergide 1.

However, the most recent and highest quality study 1 suggests that valproate can be an effective treatment for migraines, and its potential to cause headaches should be weighed against its benefits in preventing migraine attacks.

From the FDA Drug Label

CNS Effects: Sedative effects have occurred in patients receiving valproate alone but occur most often in patients receiving combination therapy. Sedation usually abates upon reduction of other antiepileptic medication Tremor (may be dose-related), hallucinations, ataxia, headache, nystagmus, diplopia, asterixis, "spots before eyes", dysarthria, dizziness, confusion, hypesthesia, vertigo, incoordination, and Parkinsonism have been reported with the use of valproate. The common side effects of Valproic Acid Oral Solution, USP include:

• nausea
• headache
• sleepiness
• vomiting
• weakness
• tremor
• dizziness
• stomach pain
• blurry vision
• double vision
• diarrhea
• increased appetite
• weight gain
• hair loss
• loss of appetite
• problems with walking or coordination

Headache is a reported side effect of valproate. However, the severity of the headache is not specified in the provided drug labels. It is essential to consult a healthcare provider for personalized advice on managing headaches associated with valproate treatment 2 2.

From the Research

Valproate and Headaches

• The studies examined the effect of valproate on headaches, including migraine and tension-type headaches.
• The results suggest that valproate can be effective in reducing the severity and frequency of headaches, including migraine attacks 3, 4, 5, 6, 7.

Efficacy of Valproate in Migraine Headaches

• A study published in 2011 found that intravenous sodium valproate was effective in aborting migraine headaches rapidly, with 75% of patients experiencing a reduction in pain from severe or moderate to mild or no pain in 60 minutes 3.
• Another study published in 2004 found that intravenous valproate was effective in managing moderate to severe headaches, with 57.5% of patients responding to treatment 4.
• A study published in 2008 found that sodium valproate was effective in reducing the maximum pain levels and pain frequency in patients with chronic daily headache, particularly those with chronic migraine 5.

Efficacy of Valproate in Tension-Type Headaches

• A study published in 1996 found that sodium valproate was not effective in reducing the frequency of chronic tension-type headaches, but had a mild effect on the migraine component of combined headaches 6.
• A study published in 2008 found that sodium valproate was less effective in reducing pain levels in patients with chronic tension-type headache compared to those with chronic migraine 5.

Comparison with Other Treatments

• A study published in 2021 found that magnesium oxide was effective in preventing migraine headache attacks, similar to valproate sodium, without significant adverse effects 7.