Role of valproic acid in the treatment of bipolar disorder

Ruolo dell'acido valproico nel trattamento del disturbo bipolare

N. Mosti, G. Perugi

Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa


Bipolar Disorder is a chronic-relapsing syndrome, defined by the occurrence of psycho-affective excitement episodes (mania, hypomania), often – but not necessarily – alternating with periods of depressive inhibition. This condition may determine an heavy quality of life impairment and can lead to the development of progressive disability. A large amount of data suggests the usefulness of Valproate both in treatment of acute manic episodes and in the prevention of affective recurrences.


The aim of the present literature review is upgrade the level of knowledge regarding efficacy and tolerability of Valproic Acid in the acute and long-term treatment of Bipolar Disorder.


An extensive examination of international literature was conducted on MEDLINE (Pubmed), PsychInfo and Scopus by using the following keywords: bipolar disorder AND valproic acid/valproate/ divalproex. Inquiry to Sanofi-Aventis and manual search of on significant chapters and reviews on the same topic has been also performed.


Available clinical studies confirm the usefulness of Valproate, both in the treatment of acute manic excitement phases and in the prophylaxis of manic and probably depressive recurrences of Bipolar Disorder. Several studies indicated a better response to Valproate than lithium in manic episodes associated with depressive component, the so-called “mixed-mania”. Other observations suggested favorable results even in patients with rapidcycling, as well as in the case of comorbidity with anxiety disorders (such as panic disorder and Post-traumatic-stress disorder). Sparse evidence, moreover, suggested the utility of Valproate in the control of alcohol and sedatives-hypnotics withdrawal symptoms. Other studies have also shown the usefulness of Valproate in the treatment of comorbid alcohol and substance use disorders, which often complicate the course of Bipolar Disorder. Concerning tolerability, Valproic Acid plays a major role, also in view of the relative safety and ease of handling compared to lithium, carbamazepine and atypical antipsychotics. Finally, the drug can easily be used as adjunctive therapy, in combination with other stabilizers, antidepressants or antipsychotics.


Valproate appears to be a reference drug for the treatment of patients with Bipolar Disorder, in its various forms, owing to its characteristics of efficacy and manageability, that allow the clinician to use it safely in various clinical situations. Future research should confirm many of the preliminary observation concerning the use of Valproate in special situations. In particular, greater attention should be devoted to the study of various drug associations that, to date, represent a very widespread practice, although not supported by adequate experimental evidence.

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