Effectiveness and safety of intravenous valproate in agitation: a systematic review

Rationale: The use of intravenous valproate is not approved for clinical practice in psychiatry. Literature data pointed out for a potential usefulness of this route of administration for valproate, but there is no actual consensus. Objectives: The aim of the present systematic review is to assess the effectiveness of intravenous valproate in agitation as well as general safety. Methods: A systematic review of studies evaluating the use of intravenous valproate in agitation was conducted. Additionally, safety was evaluated in all randomized trials involving the use of intravenous valproate in all medical conditions (epilepsy, migraine and psychiatric conditions). Results: For the systematic review on effectiveness in agitation, the search yielded 965 articles overall. After removing duplicates, 9411 articles were screened by title and abstract, and 39 of these were evaluated at a full-text level. Six studies were considered eligible for qualitative synthesis: one RCT and case report (n = 3), followed by cohort studies (n = 2). For the systematic review on safety, twenty-two RCTs were considered eligible for quantitative synthesis. Conclusion: Intravenous valproate seems efficacious in reducing agitation in psychiatric patients; it generally appears safe compared to other neuroleptics or antiepileptics. However, the evidence is still not strong as it relies mainly on open-label studies or case series.