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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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PTSD

Intervention / Treatment
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* Drug: Divalproex
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1<br>Look-a-like placebo | Other: placebo<br>* Look-a-like placebo<br>|
| Experimental: Arm 2<br>Divalproex | Drug: Divalproex<br>* anticonvulsant; mood stabilizer<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticonvulsant, anxiety, divalproex, PTSD