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As-Needed Medication Use for Agitation Across Valproic Acid Formulations.

Michael Ley1,2, Casey Tiefenthaler1, Jamie Kneebusch3

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Current Therapeutic Research, Clinical and Experimental
|February 25, 2026
PubMed
Summary
This summary is machine-generated.

Valproic acid (VPA) formulation impacts symptom control for bipolar I and schizoaffective disorder. Extended-release VPA may reduce the need for as-needed benzodiazepine and antipsychotic doses for agitation.

Keywords:
antipsychoticsbenzodiazepinesbipolar disorderschizoaffective disordervalproic acid

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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.