Inositol depletion: A good or bad outcome of valproate treatment?

Bipolar affective disorder is a severe and chronic disabling illness affecting 1.5% of the general population. Lithium, valproate and other mood stabilizers are used to treat bipolar disorder; however, these are ineffective for, and not tolerated by, a significant percentage of patients, underscoring the urgent need for better medications. Although not universally accepted, the inositol-depletion hypothesis is one of the main hypotheses suggested to explain the therapeutic mechanism of mood-stabilizing drugs. This paper reviews the relevance of the inositol-depletion hypothesis, paying special attention to the inhibition of inositol de novo synthesis by valproate. It also discusses inositol supplementation as a treatment strategy for multiple neurological disorders, including prophylactic use against valproate-induced neural tube defects.