Valproate: Clinical Pharmacological Profile

Charles L. Bowden, Vivek Singh

Research output: Chapter in Book/Report/Conference proceedingChapter


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.

Original languageEnglish (US)
Title of host publicationBipolar Psychopharmacotherapy
Subtitle of host publicationCaring for the Patient: Second Edition
PublisherJohn Wiley and Sons
Number of pages19
ISBN (Print)9780470747216
StatePublished - Apr 13 2011


  • Alcoholism
  • BDNF
  • Bipolar depression
  • Bipolar disorders
  • Combination treatment
  • Maintenance treatment
  • Mania
  • Mixed mania
  • Tolerability
  • Valproate

ASJC Scopus subject areas

  • Medicine(all)


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