Placebo Controlled Trial of Depakote ER in Alcohol Dependent Patients With Mood and/or Anxiety Symptoms
Condition: Alcoholism; Alcohol Related Disorders; Mood Disorders
MeSH terms: Alcoholism; Alcohol-Related Disorders; Mood Disorders
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study is to test the safety and effectiveness of an extended release form
      of a medication called divalproex sodium (Depakote ER) for the treatment of people with
      alcohol dependence who have mood and/or anxiety symptoms. This medication has helped reduce
      symptoms of acute alcohol withdrawal as well as stabilize mood symptoms in bipolar disorder
      and other mental health disorders. This study will test the hypothesis that divalproex sodium
      will help reduce mood and anxiety symptoms during early abstinence from alcohol and in turn
      reduce relapse and craving for alcohol.
    

Detailed description: 
      Alcohol dependence afflicts 14 million individuals in the U.S. The alcohol related costs to
      society are enormous and alcohol dependence is a significant public health problem. Although
      pharmacotherapy for the treatment of alcohol dependence and relapse prevention has expanded,
      the identification of evidence based treatment strategies is of critical importance.
      Anticonvulsants, including the divalproex sodium (DVP) formulation of valproate, have
      established effectiveness for mood disorders, and therapeutic response of mood and anxiety
      symptoms to DVP has been demonstrated in a number of psychiatric conditions. While DVP has
      been demonstrated as a treatment option for the acute alcohol withdrawal syndrome, a clear
      treatment effect has not been found in studies examining DVP for ongoing relapse prevention
      in alcohol dependence. These latter studies had limited power and excluded subjects with
      co-morbid mood and anxiety disorders, individuals who may, by extension of the former
      studies, show the greatest response to treatment with DVP. Despite the exclusion of subjects
      with mood and anxiety disorders, alcohol dependent individuals treated with DVP compared to
      placebo showed greater improvement in irritability and a trend toward greater decreases on
      measures of impulsivity and aggression. A strategy integrating the above findings would
      target treatment with DVP more specifically to alcohol dependent individuals with mood and
      anxiety disturbances.

      This randomized, double-blind clinical trial will examine the effectiveness of extended
      release DVP (Depakote-ER) in the treatment of co-morbid mood and anxiety disturbance in
      alcohol dependent subjects. The primary hypothesis is that subjects treated with Depakote-ER
      will have significantly lower scores on the Symptom Checklist (SCL-90-R) than will placebo
      treated subjects over the course of the study. Secondary hypotheses include: 1) Compared to
      placebo treated subjects, subjects treated with Depakote-ER will demonstrate significantly
      lower scores on additional measures of depression, anxiety, and irritability, 2) will have
      fewer alcohol use days and fewer drinks per drinking day, and 3) will evidence better
      retention in alcohol dependence treatment.

      Eligible subjects will complete baseline assessments and a 7-day run on Depakote-ER prior to
      randomization. After the 7-day baseline period and run in with Depakote-ER, subjects will be
      randomized and then transition to either 12 weeks of Depakote-ER or placebo, to begin upon
      completion of the 7-day run-in baseline period. Valproic acid level obtained at the end of
      the baseline period will be used to adjust the dose of Depakote-ER (or matched placebo) as
      needed to target a valproic level of 70-120 ug/ml. Dose increase, if needed, will occur with
      the study medication dispensed at the next follow up visit (scheduled for the end of the 1st
      week of active study medication or placebo). Subjects with valproic acid levels > 120 ug/ml
      at the end of the baseline period will be contacted as soon as possible and instructed to
      decrease their dose of Depakote-ER (or matched placebo) accordingly. Subjects randomized to
      the placebo condition will receive a placebo matched in number and appearance to the dosage
      of Depakote-ER prescribed during the 7-day baseline period. If needed, the number of placebo
      pills will be adjusted to match the change in the Depakote-ER dosage determined necessary
      based on the valproic acid level obtained at the end of the 7-day baseline period.

      Duration of Subject Participation: Subjects will receive either divalproex sodium extended
      release (Depakote-ER) or matched placebo for 12 weeks. Subjects will continue to receive
      other "treatment as usual" within the Addiction Treatment Center in accordance with their
      ongoing clinical program treatment plan. The standard expectation within the context of
      treatment as usual is for at least 6 months of treatment involvement. A limited number of
      psychotropic medications will be allowed during the study. A benzodiazepine (usually
      chlordiazepoxide or lorazepam, in accordance with standard practice and generally given in an
      as needed symptom triggered manner) can be prescribed during the acute detoxification period
      (first 7 days). Hydroxyzine can be prescribed PRN for anxiety, and zolpidem PRN (not to
      exceed 5 nights per week) for insomnia, throughout the course of the study.
    

Intervention name(s): divalproex sodium extended release
Intervention type(s): Drug
Intervention MeSH terms: Valproic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: alcoholism; alcohol related disorders; mood disorders; anticonvulsants; divalproex sodium