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

VA Office of Research and Development

Status and phase

Completed

Phase 3

Conditions

PTSD

Treatments

Drug: Divalproex

Other: placebo

Study type

Interventional

Funder types

Other U.S. Federal agency

Identifiers

NCT00108576

MHBS-026-01

Details and patient eligibility

About

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.

Full 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.

Enrollment

101 patients

Sex

All

Ages

19 to 65 years old

Volunteers

No Healthy Volunteers

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