As-Needed Medication Use for Agitation Across Valproic Acid Formulations

Area of Science:

• Psychiatry
• Pharmacology
• Clinical Therapeutics

Background:

• Pharmacokinetic variations exist among immediate-release (IR), delayed-release (DR), and extended-release (ER) valproic acid (VPA) formulations.
• These pharmacokinetic differences may influence treatment efficacy and patient outcomes.
• As-needed (pro re nata, PRN) medications can serve as indicators of scheduled medication effectiveness for managing agitation.

Purpose of the Study:

• To compare the number of PRN benzodiazepine and antipsychotic doses administered for agitation across different VPA formulations (IR, DR, ER).
• To investigate the association between VPA formulation and the need for PRN medications in patients with bipolar I or schizoaffective disorder.

Main Methods:

• Retrospective review of 150 patients with bipolar I or schizoaffective disorder receiving maintenance VPA therapy.
• Primary outcome: average daily PRN benzodiazepine and/or antipsychotic doses for agitation.
• Secondary outcome: VPA total daily dose (TDD). Statistical analyses included ANOVA and hierarchical multiple regression.

Main Results:

• VPA formulation was significantly associated with the average daily PRN antipsychotic and/or benzodiazepine doses, including antipsychotics alone.
• These associations remained significant after adjusting for confounders such as age, sex, race, and VPA TDD.

Conclusions:

• The formulation of VPA significantly influences the requirement for PRN medications to manage agitation.
• These findings suggest formulation-dependent differences in symptom control, warranting further investigation into optimal VPA delivery for psychiatric conditions.