Treatment of Alcohol Dependence and Comorbid Bipolar Disorder

Phase 4

Completed

• Conditions: Depression; Mania; Psychosis; Bipolar Disorder; Alcohol Dependence
• Interventions: Drug: Placebo; Drug: Lamotrigine

• Registration Number: NCT01015586
• Lead Sponsor: Medical University of South Carolina

Brief Summary

The study will determine if individuals with co-occurring bipolar disorder and alcohol dependence report reduced alcohol consumption, improvement in mood symptoms, and cognitive performance if treated with lamotrigine plus their usual mood stabilizing medications relative to subjects treated with placebo plus usual mood stabilizing medications over a 16 week period.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2009-11-17
• Study First Submitted QC: 2009-11-17
• Study First Posted: 2009-11-18
• Study Start: 2010-02
• Primary Completion: 2014-05
• Study Completion: 2014-09
• Results First Submitted: 2018-11-07
• Status Verified: 2019-01
• Results First Submitted QC: 2019-01-08
• Last Update Submitted: 2019-01-08
• Results First Posted: 2019-01-09
• Last Update Posted: 2019-01-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

• Age 18-65

• Meet DSM-IV-TR criteria for current alcohol dependence with active alcohol use in the past 30 days

• Meet DSM-IV-TR criteria for bipolar I or bipolar II disorder

• Have average alcohol consumption of at least 35 drinks/week for men, 28 drinks/week for women in the last 4 weeks of active drinking prior to enrollment.

• Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of the assessment instruments.

• Must consent to random assignment and be willing to commit to medication treatment and follow-up assessments.

• Currently under the care of a psychiatrist.

• Must consent to sign a release of information allowing investigators to communicate with his/her psychiatrist to verify treatment history and facilitate care should treatment-emergent psychiatric symptoms develop during the trial.

• Currently taking a therapeutic dosage of one or more mood stabilizing medications as defined by one or more of the following:

  • Lithium level of 0.6 - 1.2 mEq/L
  • Prescribed daily use of first generation antipsychotic agents including chlorpromazine, fluphenazine, or haloperidol or their injectible depot (decanoate) equivalents at a dose adequate to maintain clinical stability as documented by the subject's outpatient psychiatric provider c) Prescribed daily use of second generation antipsychotic agents including olanzapine, risperidone, paliperidone, quetiapine, aripiprazole, or ziprasidone or their injectible depot equivalent at a dose adequate to maintain clinical stability as documented by the subject's outpatient psychiatric provider

• Stable psychiatric symptoms as defined by no changes to psychotropic drug regimen for 30 days

• Must agree to identify collateral individuals for contact to facilitate follow-up appointments

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Exclusion Criteria

• A primary psychiatric diagnosis other than bipolar disorder
• Any uncontrolled neurologic condition (e.g. epilepsy) that could confound the results of the study
• Any history of Stevens-Johnson syndrome or other severe rash requiring hospitalization
• Any history of head injury with loss of consciousness greater than 30 minutes
• Any history of learning disability, alcoholic dementia, or electroconvulsive therapy in the past 3 months
• Any uncontrolled medical condition that may adversely affect the conduct of the trial or jeopardize the safety of the subject
• Plasma levels of liver transaminases (AST, ALT) greater than 3 times the normal range
• Concomitant use of valproic acid
• Concomitant use of carbamazepine, oxcarbazepine, phenytoin, primidone, or phenobarbital
• Concomitant use of disulfiram, naltrexone, acamprosate, or topiramate
• Concomitant use of benzodiazepines or any other medications not allowed per the protocol
• Women of childbearing potential who are pregnant, lactating, or refuse adequate forms of contraception
• Current suicidal or homicidal risk
• Baseline scores of more than 35 on the Montgomery-Asberg Depression Rating Scale or more than 16 on the Young Mania Rating Scale

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Add-on placebo plus pre-existing mood stabilization regimen for 12 weeks
Lamotrigine	Lamotrigine	Add-on lamotrigine plus pre-existing mood stabilizing medication regimen. Active fixed-dose drug titration from 25-200 mg/day over first six weeks, 200 mg/day fixed-dose maintenance for second six weeks

Primary Outcome Measures

Name	Time	Method
Percent Days Abstinent From Alcohol	12 weeks	Percentage of days in trial without consumption of alcoholic beverages per participant self-report; minimum = 0, maximum = 100; higher numbers indicate better outcome. Percent days abstinent was calculated as: (number of days abstinent per self-report / total number of days in trial)\*100.

Secondary Outcome Measures

Name	Time	Method
Percent Heavy Drinking Days	12 weeks	Percentage of days in trial that were heavy drinking days (5 or more drinks/day for men, 4 or more drinks/day for women); minimum = 0, maximum = 100; lower numbers indicate better outcome. Percent heavy drinking days was calculated as: (number of days of heavy drinking per self-report / total number of days in trial)\*100.
Biomarkers of Alcohol Use: Carbohydrate-deficient Transferrin (CDT)	12 weeks after randomization	Serum levels of biomarkers of alcohol use: carbohydrate-deficient transferrin (CDT) at study endpoint in study completers
Biomarkers of Alcohol Use: Gamma-glutamyltransferase (GGT)	12 weeks after randomization	Serum levels of biomarkers of alcohol use: Gamma-glutamyltransferase (GGT) at study endpoint in study completers
Montgomery-Asberg Depression Rating Scale (MADRS) Score	Baseline and 12 weeks	Scores on the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline (all randomized subjects) and at study endpoint (study completers). Scores represent total summed score of ten (10) subscale items; minimum = 0, maximum = 60, higher scores indicate worse outcomes.
Young Mania Rating Scale (YMRS) Scores	Baseline and 12 weeks	Mania/hypomania symptoms at study endpoint as assessed by the Young Mania Rating Scale (YMRS) at baseline (all randomized subjects) and at study endpoint (study completers). Scores represent total summed score of eleven (11) subscale items; minimum = 0, maximum = 60, higher scores indicate worse outcomes.
Neurocognitive Performance (California Verbal Learning Test)	Study endpoint 12 weeks after randomization	Adjusted scale scores (T scores) on the California Verbal Learning Test (CVLT) of verbal working memory at study endpoint. CVLT Trials 1-5 Free Recall Total measures the sum of all word list items correctly recalled on learning trials 1 through 5. This raw score is converted to a T-score (mean = 50; SD=10) with higher scores indicating better performance.

Trial Locations

Locations (1)

Clinical Neuroscience Division, Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States