Intravenous valproate in the treatment of acute manic episode in bipolar disorder: A review

E. Fontana, G. M. Mandolini, G. Delvecchio, C. Bressi, J. C. Soares, P. Brambilla

Research output: Contribution to journalReview articlepeer-review


Background: Mania is a state of elated or irritable mood characterizing Bipolar Disorder type I (BD-I). Among the pharmacological treatments for the management of mania, mood stabilizers are regularly employed, with valproate being one of the most used because of its effectiveness. However, while the oral formulation is approved for acute mania, it is unclear whether the intravenous (IV) formulation could be a valid and safe alternative. Methods: We performed a bibliographic research on PUBMED of all studies investigating the use of IV valproate as a treatment of acute mania in BD-I. A total of 13 studies met our inclusion criteria. Results: Overall, the results suggest that IV valproate as a loading therapy is an efficacious, safe and well tolerated treatment for manic episodes, and it is comparable to the oral loading regimen. Interestingly, only a few patients experienced significant side effects due to the administration of the IV valproate. Limitations: Few open label clinical trials have explored the effect of IV valproate in manic patients. Moreover, the original studies employed different clinical assessments and included manic patients taking other drugs, which made it impossible to determine whether the resolution of symptoms was due to valproate therapy alone. Additionally, serum valproate levels were not assessed by all studies. Conclusions: IV valproate may represent a valid option for the management of acute mania, with comparable effects in terms of efficacy and safety to the oral valproate. However, larger and more homogeneous studies are warranted in order to collect more precise information on the beneficial effect of IV valproate.

Original languageEnglish
Pages (from-to)738-743
Number of pages6
JournalJournal of Affective Disorders
Publication statusPublished - Jan 1 2020


  • Bipolar disorder
  • Mania
  • Mood stabilizers
  • Valproate IV

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health


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