The Food and Drug Administration has approved divalproex sodium (Depakote® and Depakote ER) from Abbott Laboratories as a prophylactic medication for migraine headache. However, divalproex sodium is not a new compound. It has been in use since 1983 for treating epilepsy and is also approved as an alternative treatment to lithium for bipolar disorder. Several clinical trials have demonstrated its effectiveness in migraine prevention.

It should be considered as another therapy for migraine prevention. It is ranked by the US Headache Guidelines Consortium as being equal in effectiveness and safety to propranolol, timolol and amitriptyline for the preventive treatment of migraine. Those patients who have other medical problems in addition to migraine, including cardiovascular diseases, seizures or bipolar disorder, may be excellent candidates for this agent.

Side effects with the medication may include nausea, stomach upset, diarrhea, vomiting, weakness, fatigue, sleepiness, dizziness, hair loss, tremor and weight gain. These tend to be mild and transient in most patients and may be minimized by slow upward dosing of divalproex sodium and use of the ER (extended-release) formulation. Liver function tests should be obtained for evidence of adverse effects if the patient experiences signs of liver dysfunction such as jaundice or persistent nausea. Women who are in their childbearing years and who are contemplating pregnancy or who are not using contraception should be especially cautious with this medication as it may cause birth defects if taken during pregnancy. Women on this medication should also take Folic Acid 4 mg daily to decrease the risk of birth defects should she become pregnant.

The initial dose is 250 mg twice per day. This is effective for many patients. However, higher doses of Depakote® are commonly used. In migraine prevention, doses of 750 to 1500 mg per day are optimal for many patients. The dose can be divided with the standard direct release tablet or given as a bedtime only dose when used at doses of 1000 mg or less. This may reduce side effects. Recently the ER version has become available offering true once-daily dosing of 500-1500 mg nightly. Side effects with the extended release formulation were approximately those of placebo during the clinical trial. Monitoring of blood levels of the medication to attain a therapeutic level is not needed but may be useful especially at high doses to reduce risks of toxic side effects.