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Excerpt 2
James W. Jefferson, MD and John H. Greist, MD

Divalproex & Bipolar Disorder: A Guide

(Excerpt 1)

Divalproex (pronounced dye-VAL-pro-ex) is a medication that has been used for many years to treat certain forms of epilepsy. More recently, it has been shown to be an effective treatment for bipolar (manic-depressive) disorder, and its use in psychiatry has been expanding. It has become a well-accepted treatment for acute manic episodes and other aspects of manic-depressive disorder.

Divalproex, more formally know as divalproex sodium and more commonly known by its brand name, Depakote, was first approved by the United States Food and Drug Administration (FDA) for the treatment of epilepsy. In May, divalproex was FDA-approved for the treatment of manic episodes associated with bipolar disorder. It is also used for the long-term treatment of bipolar disorder, and research is currently being conducted to further evaluate its effectiveness in this regard. In July, divalproex was FDA-approved for the prevention of migraine headaches.

Divalproex is what is referred to as a co-ordination compound. It consists of equal amounts of sodium valproate (pronounced val-PRO-ate) and valproic (pronounced val-PRO-ic) acid. Divalproex is converted to the valproate ion in the gastrointestinal tract; hence, the term valproate is often used to refer to divalproex and another form of valproate known as valproic acid. In this latter form, valproate was used to treat epilepsy in Europe and was approved by the FDA for this indication. Because divalproex is the form of valproate approved by the FDA for the treatment of mania, and because it is prescribed much more often than valproic acid, the terms "divalproex" and "Depakote" will be used in this booklet. Most of the content, however, is just as applicable to valproic acid (Depakene).

Both forms of valproate (divalproex sodium and valproic acid) are taken by mouth in the form of tablets, capsules, or syrup-all of which require a doctor�s prescription. While the brand name of divalproex in the United States is Depakote, it is called Epival in Canada. At present there are no generic preparations of divalproex. It is available in tablet form (referred to as divalproex sodium delayed-release tablets or Depakote) in dosage sizes of 125 mg, 250 mg, and 500 mg. There is also a 125 mg sprinkle capsule of Depakote that can be swallowed or opened and sprinkled over food. Divalproex sodium extended-release tablets (Depakote ER) (250 mg and 500 mg tablets) was approved recently by the FDA for prophylaxis of migraine headaches in adults and is also being used for bipolar disorder. Swiching from Depakote to Depakote ER may require some dose adjustment because blood levels of the ER were found to be lower when equal doses of the two preparations were compared.

Another valproate preparation is valproic acid, whose brand name is Depakene in both the United States and Canada. Generic preparations of valproic acid are also marketed. It is available in capsules (250 mg) and in syrup (5 ml or about 1 teaspoon contains 250 mg). Finally, a solution of valproate sodium (Depacon) is available for injection into a vein to treat certain seizure conditions.