3. Valproate: Clinical Pharmacological Profile

  1. Hagop S. Akiskal2 and
  2. Mauricio Tohen3
  1. Charles L. Bowden and
  2. Vivek Singh

Published Online: 13 APR 2011

DOI: 10.1002/9780470975114.ch3

Bipolar Psychopharmacotherapy: Caring for the Patient, Second Edition

Bipolar Psychopharmacotherapy: Caring for the Patient, Second Edition

How to Cite

Bowden, C. L. and Singh, V. (2011) Valproate: Clinical Pharmacological Profile, in Bipolar Psychopharmacotherapy: Caring for the Patient, Second Edition (eds H. S. Akiskal and M. Tohen), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470975114.ch3

Editor Information

  1. 2

    International Mood Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0603, USA

  2. 3

    Department of Psychiatry, Division of Mood and Anxiety Disorders, University of Texas Health Science Centre at San Antonio, 7730 Floyd Curl Drive, San Antonio, TX 78229, USA

Author Information

  1. Department of Psychiatry, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio TX 78229-3900, USA

Publication History

  1. Published Online: 13 APR 2011
  2. Published Print: 15 APR 2011

ISBN Information

Print ISBN: 9780470747216

Online ISBN: 9780470975114



  • valproate;
  • bipolar disorders;
  • mania;
  • bipolar depression;
  • mixed mania;
  • BDNF;
  • maintenance treatment;
  • combination treatment;
  • tolerability;
  • alcoholism


Objective: This review aims to outline the evidence for the acute and long term efficacy and tolerability of valproate in the management of bipolar disorders, in both adults and adolescent populations. Additionally, determinants of favorable or unfavorable outcomes are described.

Method: The authors reviewed published studies and abstracts from 2000 onwards. Emphasis was placed on randomized, placebo-controlled prospective studies.

Result: Recent studies hypothesize valproate's inhibition of histone deacetylase and glycogen synthase kinase, and activation of extracellular signal-regulated kinase to be relevant to its actions in bipolar disorders and overlap with postulated mechanism of actions of lithium. Valproate demonstrates both efficacy and tolerability in the treatment of acute mania, and is somewhat more effective in certain patient subgroups, for example, mixed mania, and mania with prominent irritability, in comparison to other treatments. Valproate demonstrates comparable efficacy but superior tolerability to olanzapine in maintenance treatment. Serum levels greater than 110 µg/ml are associated with higher prevalence of weight gain, sedation, and thrombocytopenia. Valproate may be associated with an increased rate of polycystic ovarian syndrome, with higher risks in those with increased weight. Several studies indicate that valproate can be safely and beneficially combined with antipsychotic drugs and other treatments for bipolar disorder.

Conclusion: Valproate continues to be studied in further clarification of its mechanisms, efficacy, risks, and spectrum of benefits in bipolar disorder. Evidence from studies in the past two decades demonstrates that valproate is a major treatment, both as monotherapy and in combination with other agents, for the acute and long term treatment of bipolar disorders.