Disodium valproate: new preparation. An alternative for acute mania after lithium failure or intolerance

(1) The reference treatment for mania is lithium. Lithium can be combined with a neuroleptic in patients who also have psychotic disorders (especially with aggressiveness). Carbamazepine is a second-line alternative. (2) Marketing authorisation has now been granted in France for disodium valproate (divalproate). (3) Disodium valproate is a complex composed of one molecule of sodium valproate and one molecule of valproic acid. Its effects are identical to those of valproate sodium. (4) The clinical file on disodium valproate mainly comprises two double-blind trials. In one trial involving 43 patients in whom lithium was ineffective or poorly tolerated, the efficacy of divalproate, measured using a validated scale, was significantly superior to that of the placebo. (5) The other trial, involving 179 patients, confirmed the efficacy of divalproate versus a placebo, and showed that divalproate was roughly as effective as lithium. (6) The efficacy of divalproate has not been compared with that of carbamazepine. It has not yet been demonstrated that carbamazepine remains effective when lithium is inadequate. (7) The adverse effect profile of divalproate mainly comprises gastrointestinal and neuropsychological disorders. A few cases of severe hepatitis and pancreatitis have also been reported. (8) In practice, in cases of lithium intolerance or inefficacy, divalproate is worth trying for patients with acute mania, before trying carbamazepine.