Inpatient Use of Valproic Acid in Agitated Delirium by Palliative Medicine

Background: Antipsychotics and benzodiazepines are prescribed for hyperactive delirium despite their side effects and lack of supportive evidence. Valproic Acid (VPA) improves agitation without QTc prolongation, excessive sedation, and parkinsonism. However, high quality evidence for this is lacking in delirium. Methods: This retrospective study involved hospitalized patients seen by Palliative medicine from 10/1/2019 to 4/17/2020 who received VPA for at least 24 hours for hyperactive delirium. Patients were excluded if VPA was used for seizures or bipolar disorder. We hypothesized that VPA improves agitation and thus reduces the use of opioids, antipsychotics, and benzodiazepines. Results: Twenty patients, 50% women, and a median age of 81.5 years were treated. Nine had cancer, five dementia and two had strokes. The median daily VPA dose was 831.6 mg (IQR 671.4 -1016.4). Due to the small numbers, we did not find a statistically significant differences in benzodiazepine, opioid, or antipsychotic use on days 1, 2, or 3. VPA was used as monotherapy in 10 patients, with no additional antipsychotic or benzodiazepines needed. Eleven patients were on comfort care measures at the time of VPA initiation. Ten died in the hospital. Three were discharged home, and seven transferred to a skilled nursing facility. Discussion: This study explored the use of VPA in palliative care. VPA may be effective in treating aggitation. Randomized controlled trials are needed to validate VPA benefits in treating agitated delirium.