Valproic Acid in the Management of Delirium.

CONTEXT: Antipsychotics and benzodiazepines do not improve delirium. Valproic acid (VPA) has been used recently to treat agitation in delirium.

OBJECTIVES

To review the evidence for VPA in the management of Delirium.

METHODS

Systematic review. English language, age 19 and above, from 1946 to January 12, 2021.

MESH TERMS: "Valproic acid", "valproate", "sodium valproate", "delirium", "acute mania with delirium" in PubMed and Ovid.

EXCLUSION: Studies of VPA used for diagnoses other than delirium.

RESULTS

21 abstracts were identified and 10 studies were included in the review (252 patients): One prospective open label study (n: 7), 2 case series (n: 22), 4 retrospective studies (n: 219) and 3 case reports (n: 4). No randomized controlled trial (RCT) evaluates the effect of VPA in delirium. 237/250 (94.8%) patients were in the ICU. Mean age was 59.7 (27-87). 153/204 (74%) were male. The mean starting dose was 733 mg/day in 148 patients and the mean dose at follow up was 1061 mg/day in 205 patients. CAM ICU was used to diagnose delirium in 6 reviews. Delirium improved in case series in 19/22 patients. Delirium improved in retrospective studies at day 3 compared to day 1. VPA levels were not consistently reported. Hyperammonemia (12-19%) and thrombocytopenia (9-13%) were the most common side effects. No deaths were attributed to VPA.

CONCLUSION

VPA is being used more frequently for delirium. The evidence is limited to retrospective studies and case series. There is a need for RCT to evaluate the effect of VPA in delirium compared to other alternatives and placebo.