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A Case Series Examining the Use of Valproic Acid for Agitation Management After a Traumatic Brain Injury

Nicole Diaz-Segarra, MD (Kessler Institute for Rehabilitation/Rutgers-New Jersey Medical School, West Orange, New Jersey); Ondrea McKay, MD; Peter Yonclas, MD

Meeting: AAPM&R Annual Assembly 2020

Categories: Neurological Rehabilitation (2020)

Session Information

Session Title: Virtual Poster Hall

Session Time: None. Available on demand.

Disclosures: Nicole Diaz-Segarra, MD: No financial relationships or conflicts of interest

Case Description: Agitation management using valproic acid after a traumatic brain Injury

Setting: Acute Hospital

Patient: Three male patients ages 36-69 years-old were admitted to the hospital after sustaining a moderate to severe traumatic brain injury (TBI). Assessment/

Results: During their hospitalization, they exhibited varying degrees of agitation ranging from restlessness to aggression. They were started on one to three medications to treat agitation including lipophilic beta-blockers, atypical antipsychotics, and membrane stabilizers without significant improvement, with Richmond Agitation-Sedation Scale (RASS) varying from +2 to +4. Valproic acid (VPA) was then initiated in doses ranging from 250mg daily to 1000mg daily with improvement in RASS score to -2 to +1. VPA was utilized for seven to twenty days prior to discontinuation with no observed elevation in liver function tests (LFTs).

Discussion: Agitation is common acutely after a TBI, varying from restlessness to aggressive behaviors. VPA offers multiple advantages over other medications for the off-label management of agitation because it lacks anticholinergic properties, has a low risk of extrapyramidal symptoms, and does not have cardiac or respiratory side effects. The total daily recommended dose is 500 mg to 2000 mg with the common side effects of nausea, vomiting, and sedation at high doses. Minor LFT elevations occur in 5-10% of patients receiving long term treatment, resolving after discontinuation, with uncommon reports of fatal hepatoxicity. These cases highlight that VPA can be used for agitation management in patients with TBI and is well tolerated with short-term use.

Conclusion: The short-term use of VPA, either alone or in combination, can be considered for agitation management in TBI patients. Caution should be used in patients with liver disease and LFTs monitored at frequent intervals while on VPA. Additional studies are needed to characterize its use to manage agitation after TBI including optimal dosage, monitoring, side effects, and comparison to other commonly used medications.

Level of Evidence: Level V

To cite this abstract in AMA style:

Diaz-Segarra N, McKay O, Yonclas P. A Case Series Examining the Use of Valproic Acid for Agitation Management After a Traumatic Brain Injury [abstract]. PM R. 2020; 12(S1)(suppl 1). https://pmrjabstracts.org/abstract/a-case-series-examining-the-use-of-valproic-acid-for-agitation-management-after-a-traumatic-brain-injury/. Accessed May 8, 2025.
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