As-Needed Medication Use for Agitation Across Valproic Acid Formulations

Background: Pharmacokinetic differences between immediate-, delayed- and extended-release (IR, DR, ER) formulations of valproic acid (VPA) may impact therapeutic outcomes. As-needed, pro re nata (PRN) medications may serve as proxies for scheduled medication effectiveness for symptom management. This study compared the number of PRN doses of benzodiazepines and antipsychotics for agitation between VPA formulations. Methods: A retrospective review was conducted for patients with bipolar I or schizoaffective disorder who received three or more days of VPA (IR, DR, ER) doses as maintenance therapy. The primary outcome was the difference in average daily number of PRN benzodiazepine and/or antipsychotic doses for agitation across formulations. The secondary outcome included differences in VPA total daily dose (TDD) across formulations. Descriptive statistics, ANOVA, and hierarchical multiple regression analyses were used for comparisons. Results: A total of 150 patients were included (59% male, 55% Caucasian). The VPA formulation was significantly associated with the average daily PRN antipsychotic and/or benzodiazepine doses, as well as antipsychotic alone, after adjusting for potential confounders (age, sex, race, psychiatry unit, average VPA total daily dose). Conclusion: The significant difference in the number of PRN benzodiazepine and/or antipsychotic doses administered for agitation among the different formulations of VPA may suggest differences in symptom control. Further investigation is warranted.