Divalproex Sodium in the Treatment of PTSD (Post-Traumatic Stress Disorder)

Divalproex Sodium in the Treatment of PTSD: A Placebo-Controlled Study

The purposes of this study are:

• To study the efficacy of divalproex in the treatment of PTSD;
• To study the plasma GABA (gamma aminobutyric acid) levels before and after treatment with divalproex in PTSD.

Study Overview

• Status: Completed
• Conditions: PTSD
• Intervention / Treatment: Other: placebo; Drug: Divalproex

Detailed Description

Objective: To study the efficacy of divalproex in the treatment of PTSD. Research Design: This is an 8-week randomized, double-blind, placebo-controlled treatment trial of divalproex.

Methodology: After signing an informed consent and meeting all inclusion/exclusion criteria, the patient is randomized to either divalproex or placebo for an 8-week duration. During the study a pharmacist maintains the randomization log and administers the placebo or divalproex (500 mg/capsule) in look-a-like tablets. Patients' symptoms, side effects and compliance are assessed bi-weekly. Based on symptomology and occurrence of side effects, the investigator increases the medication in 500 mg (one tablet) increments every four days, as tolerated, until a maximum therapeutic benefit is achieved, not to exceed 3000 mg/day (6 capsules). The dosing is twice daily, with the higher dose at bedtime. Compliance is assessed by bi-weekly pill count and blinded valproic acid levels at week 4 and week 8. Patients are given supportive clinical management during the clinic visits. An investigator is available by telephone 24 hrs a day in case of emergency. Patients may be seen more often if needed. Efficacy will be measured by the following assessment scales: MADRS (Montgomery-Asberg Depression Rating Scale), Ham-A (Hamilton Anxiety Scale), CGI-s (Clinical Global Impressions-Severity of Illness Scale), CGI-I (Clinical Global Impressions-Improvement Scale), GAF (Global Assessment of Functioning), CAPS (Clinician-Administered PTSD Scale), TOP-8 (Treatment Outcome PTSD Rating Scale), and DTS (Davidson Trauma Scale). Results of this study will be used to evaluate the efficacy of divalproex in the treatment of PTSD.

Significance: Divalproex has shown promise in treating PTSD in open label trials. This study is the next step in proving divalproex's efficacy in the treatment of PTSD.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35404
      • Tuscaloosa VA Medical Center, Tuscaloosa, AL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of PTSD, confirmed by MINI (Mini-International Neuropsychiatric Interview) and CAPS
• Age 19 or older
• No substance abuse/dependence for the previous 6 weeks (except for nicotine and caffeine)
• Free of psychotropic medication for 2 weeks (except 6 weeks for fluoxetine)
• Clinically normal physical and laboratory examination (lab profile listed below). LFTs (liver function tests) up to 2.5 times the normal limit will be allowed.
• Women of childbearing potential must be using medically approved methods of birth control (such as a condom, birth control pill, Depo-Provera, or diaphragm with spermicides)
• Signed informed consent
• Male or female of any race or ethnic origin

Exclusion Criteria:

• Lifetime history of bipolar I, psychotic, or cognitive disorders
• Actively suicidal, homicidal, or psychotic
• History of sensitivity to divalproex
• Unstable general medical conditions
• Score 6 on Question #10 of MADRS
• Women who are pregnant, planning to become pregnant or to breastfeed during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Arm 1; Look-a-like placebo	Other: placebo; Look-a-like placebo
EXPERIMENTAL: Arm 2; Divalproex	Drug: Divalproex; anticonvulsant; mood stabilizer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinician Administered PTSD Scale (CAPS)	8weeks

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Lori Lynne Davis, MD AB, Tuscaloosa VA Medical Center, Tuscaloosa, AL

Publications and helpful links

General Publications

• Davis LL, Davidson JR, Ward LC, Bartolucci A, Bowden CL, Petty F. Divalproex in the treatment of posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial in a veteran population. J Clin Psychopharmacol. 2008 Feb;28(1):84-8. doi: 10.1097/JCP.0b013e318160f83b.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (ACTUAL): August 1, 2005
• Study Completion (ACTUAL): September 1, 2005

Study Registration Dates

• First Submitted: April 15, 2005
• First Submitted That Met QC Criteria: April 15, 2005
• First Posted (ESTIMATE): April 18, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): October 21, 2015
• Last Update Submitted That Met QC Criteria: October 20, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: PTSD; anxiety; anticonvulsant; divalproex
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; GABA Agents; Anticonvulsants; Antimanic Agents; Valproic Acid
• Other Study ID Numbers: MHBS-026-01