Adjunctive Topiramate for Treatment of Alcohol Dependence in Patients With Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

Adjunctive Topiramate for Treatment of Alcohol Dependence in Patients With Bipolar Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00572117
• Other study ID #: TIL-NIAAA-016340-01
• Secondary ID: K23AA016340
• Status: Completed
• Phase: Phase 4
• First received: December 10, 2007
• Last updated: November 16, 2015
• Start date: August 2007
• Est. completion date: July 2014

Study information

• Verified date: November 2015
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is determine whether the use of topiramate is effective in the treatment of alcohol dependence (i.e. decreases drinking) in patients with bipolar disorder.

Description:

Alcohol and substance use disorders are more common in bipolar disorder bipolar disorder than in any other DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) Axis I disorder, estimated to occur in up to 60% of patients with bipolar disorder. Alcohol use is associated with poor outcome in bipolar disorder, and yet these co-occurring conditions are understudied. To date, there is only one published placebo-controlled trial of an agent for the treatment of alcohol dependence alcohol dependence in bipolar disorder. The purpose of the proposed study is to evaluate the efficacy of a topiramate as a treatment for alcohol dependence in patients with bipolar disorder. This is a 12-week, randomized, placebo-controlled study of the efficacy of topiramate adjunctive to standard treatment for bipolar disorder in patients with alcohol dependence and bipolar disorder. Additional aims of the study are to document the safety and tolerability of topiramate in this population, and to evaluate to effect of decreased drinking on mood symptoms. The study involves the enrollment of a total of 80 patients with co-occurring alcohol dependence and bipolar disorder over the course of 40 months at the Massachusetts General Hospital (MGH) Bipolar Clinic and Research Program (BCRP) (www.manicdepressive.org). With a conservative estimate of a 30% dropout rate, approximately 56 of the 80 patients with these two comorbid conditions will complete 12 weeks treatment with either topiramate or placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2014
• Est. primary completion date: July 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18+

2. Written informed consent.

3. Meet DSM-IV criteria (by SCID) for alcohol dependence.

4. Meet DSM-IV criteria (by SCID) for bipolar disorder I or II disorder.

5. = 8 heavy drinking days (defined as = 5 standard drinks per day for men, = 4 standard drinks per day for women) in the prior 4 weeks.

6. During the baseline visit, patients must be on a stable dose of accepted maintenance treatment for bipolar disorder for the past 4 weeks. If the subject is on more than one agent, at least one agent must be adequately dosed.

7. Antidepressant treatment is permitted if the dose has been stable for the past 4 weeks.

Exclusion Criteria:

1. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy). Because of the risk of the lowering of oral contraceptive blood levels with topiramate, women whose sole means of contraception is oral contraceptives or hormonal implants will be asked to use an additional barrier method of birth control during treatment with the study drug.

2. Women who are lactating.

3. Age under 18.

4. Patients who do not have = 8 heavy drinking days in the 4 weeks prior to the baseline visit.

5. Important alcohol withdrawal symptoms (Clinical Institute Withdrawal Assessment for Alcohol-Revised, CIWA-Ar, score > 15)

6. Urine toxicological screen positive for amphetamines or cocaine.

7. Meets DSM-IV criteria for current substance dependence for drugs other than cannabis or nicotine.

8. Currently meets full DSM-IV criteria for manic, hypomanic, or mixed episode.

9. Serious suicide or homicide risk, as assessed by evaluating clinician.

10. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease or uncontrolled seizure disorder.

11. History of nephrolithiasis, or treatment with any drug associated with nephrolithiasis.

12. Current treatment with zonisamide.

13. Current treatment with any carbonic anhydrase inhibitors, including acetazolamide, dorzolamide, and methazolamide.

14. Current treatment with any drug known to decrease drinking.

15. Subjects who have begun a new psychosocial treatment within 12 weeks of study enrollment. Subjects receiving psychosocial treatment that has been stable for at least 12 weeks prior to study entry, however, will be permitted to enroll in the study.

16. Any psychotic disorder, including schizoaffective disorder (current or past).

17. Clinical or laboratory evidence of untreated hypothyroidism.

18. Patients with a diagnosis or history of glaucoma

19. Patients requiring excluded medications (see table below for details).

20. Psychotic features in the current episode or a history of a psychotic disorder, as assessed by SCID.

21. Past intolerance to topiramate.

22. Any use of topiramate in the past 12 months.

23. Any investigational psychotropic drug within the last 3 months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alcohol Dependence
• Alcoholism
• Bipolar Disorder
• Disease

Intervention

Drug:
• Topiramate
Medication will be slowly increased over 5 weeks from 25 mg a day to 150 mg twice a day in an effort to minimize side effects that might enable participants and raters to guess whether they are on active drug or placebo. Subjects will continue on 150 mg twice a for Weeks 6-12 of the study.

Locations

Country	Name	City	State
United States	Stanford/VA Palo Alto Mood Disorder Research Program	Palo Alto	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amount of alcohol consumed		12 Weeks	Yes
Secondary	Safety and tolerability of topiramate.		12 Weeks	Yes
Secondary	Effect of decreased drinking on mood symptoms		12 Weeks	Yes

External Links

•   Stanford/VA Palo Alto Bipolar and Depression Research Program