Topiramate Treatment of Alcohol Use Disorders in Veterans With Post Traumatic Stress Disorder (PTSD): A Pilot Controlled Trial of Augmentation Therapy
Condition: PTSD; Alcohol Abuse; Alcoholism
MeSH terms: Alcoholism; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Topiramate; Placebo administration
Intervention description: After random assignment, topiramate will be titrated up over 5 weeks. Dosing begins at 25 mg per day, and increase in the second week to 25 mg twice per day; in the third week to 50 mg twice/day; in the fourth week to 75 mg twice/day; in the 5th week to 100 mg twice/day; and in weeks 6-11 increased to and maintained at 100 mg in the morning and 200 mg at night. Patients will receive the highest dose tolerated, not to exceed 300 mg per day. Adjustments are permitted throughout titration. Once maximum tolerated dosage is reached, subjects will be asked to maintain dosage for remainder of the treatment phase. Upon completing the 6 week maintenance period subjects will taper off over a 7-day period (Week 12). If subjects experience significant side effects, the dosage may be adjusted.; Placebo pills will be prepared by the UCSF pharmacy which will be indistinguishable from the topiramate pills used in that arm. Both topiramate and placebo will then be delivered to the VA pharmacy. A consulting biostatistician will randomly assign participants to either the topiramate or placebo group. The dosing of placebo pills will follow the same regimen as outlined for the topiramate arm. In the event of a safety issue, there will be a procedure for unblinding only that participant.
Intervention MeSH terms: Topiramate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PTSD; Alcohol abuse; Alcoholism; Topiramate; Stress Disorder, Post Traumatic; Chronic Post-Traumatic Stress Disorder

Summary:

      The proposed project aims to:

        1. Obtain a preliminary assessment of the efficacy of topiramate treatment in reducing
           alcohol use in veterans with Post Traumatic Stress Disorder (PTSD) and alcohol
           dependence;

        2. Obtain preliminary assessments of safety/tolerability of topiramate in these patients;

        3. Assess the feasibility of recruitment and retention for topiramate treatment in this
           comorbid population; and 4) to inform the design of a planned subsequent larger
           controlled trial of topiramate.

      PRIMARY HYPOTHESIS: Topiramate treatment combined with Medical Management alcohol counseling
      will be associated with a significant decrease in percent drinking days from baseline to end
      of treatment.

      SECONDARY HYPOTHESIS: There will be significantly less percent drinking days in the
      topiramate treatment group compared to the placebo group.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female outpatient veterans.

          -  Current DSM-IV diagnosis of PTSD.

          -  Current (past month) DSM-IV diagnosis of an Alcohol Use Disorder.

          -  Must meet criteria for "heavy" or "at-risk" drinking by NIAAA thresholds.

          -  Receiving treatment for PTSD.

          -  Must express desire to reduce alcohol consumption.

          -  Female subjects must have negative urine pregnancy test and must be either
             postmenopausal for at least one year, or practicing an effective method of birth
             control.

          -  Must have a BAC of less than 0.02% when signing the informed consent.

        Exclusion Criteria:

          -  Psychotic disorders, bipolar disorder, dementia, or other psychiatric disorders judged
             to be unstable.

          -  Subjects known to have clinically significant unstable medical conditions, including
             but not limited to: clinically significant renal disease and/or impaired renal
             function as defined by clinically significant elevation of BUN or creatinine or an
             estimated creatinine clearance of < 60 mL/min; AST (SGOT) and/or ALT (SGPT) >3 times
             the upper limit of the normal range and/or an increased serum bilirubin >2 times the
             upper limit of normal; seizure disorders.

          -  Subjects with glaucoma.

          -  Subjects with a history of kidney stones.

          -  Subjects with a history of renal disease.

          -  Concurrent participation in another treatment study.

          -  Female patients who are pregnant or lactating.

          -  Current topiramate use or use within the past 4 weeks.

          -  Current medications for alcohol dependence or use within the past 4 weeks.

          -  Needing acute medical detoxification from alcohol based on a score of 12 or more on
             the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-AD);

          -  Subjects who are legally mandated to participate in an alcohol treatment program.

          -  Subjects who have had a suicide attempt or suicidal ideation in the 6 months prior to
             enrollment.

          -  Subjects who have previously been treated with topiramate for any reason and
             discontinued treatment due to an adverse event or due to a hypersensitivity reaction
             to topiramate,

          -  Subjects with seizure disorders that require anticonvulsant medications

          -  Subjects currently being treated with another anticonvulsant.

          -  Subjects who in the opinion of the investigator should not be enrolled in the study
             because of the precautions,warnings or contraindications outlined in the topiramate
             package insert.