Alcohol Abuse, Bipolar Disorder
Conditions
Keywords
Adolescents
Brief summary
The purpose of this research study is to study the effects (both good and bad) of combining quetiapine and topiramate for treating symptoms of bipolar mania (an illness with periods of elation, excessive excitement, irritability, high energy, racing thoughts, poor sleep, poor judgment, reckless behavior) and to study the effects (both good and bad) of combining quetiapine and topiramate for reducing use of alcohol.
Detailed description
Specific Aim 1: To collect preliminary data regarding the efficacy and tolerability of topiramate for the treatment of alcohol use disorders (alcohol abuse and dependence) in adolescents with bipolar disorder. Hypothesis 1: We hypothesize that topiramate in combination with quetiapine will lead to greater reduction in alcohol consumption (number of drinks per day, number of drinks per drinking day, and number of heavy drinking days) and greater abstinence (percentage of days abstinent) compared with quetiapine alone. Specific Aim 2: To obtain preliminary data regarding the efficacy of topiramate for reducing manic symptoms in adolescents with co-occurring alcohol use and bipolar disorders. Hypothesis 2: We hypothesize that the topiramate in combination with quetiapine will produce greater reduction in Young Mania Rating Scale (YMRS) scores than quetiapine alone.
Interventions
Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1 Dosing Schedule and Titration of Topiramate: All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner. Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4.
Sponsors
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 12-25 years; 2. DSM-IV-TR83 criteria for bipolar disorder, type I, manic or mixed episode; 3. Young Mania Rating Scale (YMRS)86-88 score of \> 16 at screening and baseline visits; 4. DSM-IV-TR83 criteria for current alcohol abuse or dependence; 5. Drinking \>8 drinks in 30 days within the previous 6 months while meeting DSM-IV criteria for alcohol abuse or dependence. One standard drink is defined as 0.35 liters of beer, 0.15 liters of wine, or 0.04 liters of 80-proof liquor; 6. Fluent in English; 7. Provision of written informed consent/assent; 8) If female and of child bearing potential, agrees to use one of the following method of birth control: complete abstinence, barrier (diaphragm or condom), or oral contraceptive containing \> 35 micrograms of ethinyl estradiol (because concomitant use of topiramate and lower estrogen oral contraceptives may lead to contraceptive failure).
Exclusion criteria
1. Manic symptoms resulting from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by medical evaluation and rapid symptom resolution; 2. Clinically significant alcohol or drug withdrawal symptoms that have the potential to cause serious consequences as determined by vital signs, the CIWA-Ar,84 and medical evaluation; 3. Any unstable medical illness or laboratory abnormalities \> 3 times upper limits of normal; 4. A documented history of mental retardation or an IQ total score \< 70 as determined by the Wechsler Abbreviated Scale of Intelligence (WASI),154 administered by a trained psychometrician; 5. Any substance use other than alcohol, nicotine, or cannabis during the 30 days prior to study participation; 6. A positive urine pregnancy test or lactating; 7. History of nephrolithiasis. 8. Treatment with concurrent mood stabilizers, antipsychotics or antidepressants; 9. Treatment with antipsychotics or other mood stabilizers within 72 hours and antidepressants within 5 days prior to randomization; 10. Treatment with fluoxetine within one month; 11. A history of non-response or hypersensitivity to quetiapine or topiramate; 12. Serious suicidal ideation (\> 3 on the CDRS-R89 suicide item, or any serious suicide attempt within the prior 60 days as judged by the investigator; 3=has thoughts about suicide or hurting themselves usually when angry); 13. Treatment for substance use during 30 days prior to screening (excluding peer support groups); 14. Court-ordered to substance use treatment; 15. Acute intoxication; 16. History of a medication change during the prior 30 days that may have precipitated manic symptoms; 17. History of a partial response (any improvement) to any existing medications as reported by treating clinician, subjects or legal guardian.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Drinks Per Day | baseline to 12 weeks or endpoint (up to 11 weeks) | Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period). |
| Drinks Per Drinking Day | baseline to 12 weeks or endpoint (up to 11 weeks) | Change in drinks/drinking day (number of drinks consumed divided by the number of days during which alcohol was consumed during that study period) |
| Percentage of Days Abstinent | baseline to 12 weeks or endpoint (up to 11 weeks) | Change in percent days abstinent (the number of non-drinking days divided by the number of days in that study period). |
| Percent Heavy Drinking Days | baseline to 12 weeks or endpoint (up to 11 weeks) | Change in percent heavy drinking days (number of days of \> 4 drinks/day divided by number of days in that study period). |
Countries
United States
Participant flow
Recruitment details
56 study participants were consented for study participation, of which 17 were screen fails.
Pre-assignment details
56 study participants were consented for study participation, of which 17 were screen fails.
Participants by arm
| Arm | Count |
|---|---|
| Quitiapine and Placebo Quetiapine and Placebo
quetiapine and placebo: Dosing Schedule and Titration of Quetiapine: open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1
Dosing Schedule and Titration of Topiramate:
All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner.
Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4. | 21 |
| Quitiapine andTopiramate Quetiapine and Topiramate
Quetiapine andTopiramate: Dosing Schedule and Titration of Quetiapine:
open-label quetiapine beginning day 1 at 100 mg/day titrated to 400 mg/day by the end of week 1
Dosing Schedule and Titration of Topiramate:
All subjects will be randomized to topiramate or matching placebo which will be administered in a double-blind manner.
Topiramate/Placebo titrated from 25 mg twice daily to 150 mg bid by week 4. | 18 |
| Total | 39 |
Baseline characteristics
| Characteristic | Quitiapine andTopiramate | Quitiapine and Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 18 Participants | 21 Participants | 39 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 17.7 years STANDARD_DEVIATION 2.4 | 18 years STANDARD_DEVIATION 3.1 | 17.9 years STANDARD_DEVIATION 2.7 |
| Region of Enrollment United States | 18 participants | 21 participants | 39 participants |
| Sex: Female, Male Female | 8 Participants | 16 Participants | 24 Participants |
| Sex: Female, Male Male | 10 Participants | 5 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 21 | 11 / 18 |
| serious Total, serious adverse events | 8 / 21 | 2 / 18 |
Outcome results
Primary
Drinks Per Day
Change in self-reported drinks/day (drinks consumed divided by the number of days during that study period).
Time frame: baseline to 12 weeks or endpoint (up to 11 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine + Placebo | Drinks Per Day | -1.4 Drinks per day | Standard Deviation 2.3 |
| Quetiapine + Topiramate | Drinks Per Day | -2.4 Drinks per day | Standard Deviation 5.1 |
Primary
Drinks Per Drinking Day
Change in drinks/drinking day (number of drinks consumed divided by the number of days during which alcohol was consumed during that study period)
Time frame: baseline to 12 weeks or endpoint (up to 11 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine + Placebo | Drinks Per Drinking Day | -7.2 Drinks per drinking day | Standard Deviation 10.2 |
| Quetiapine + Topiramate | Drinks Per Drinking Day | -7.3 Drinks per drinking day | Standard Deviation 6 |
Primary
Percentage of Days Abstinent
Change in percent days abstinent (the number of non-drinking days divided by the number of days in that study period).
Time frame: baseline to 12 weeks or endpoint (up to 11 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine + Placebo | Percentage of Days Abstinent | 15 Percentage of days abstinent | Standard Deviation 19 |
| Quetiapine + Topiramate | Percentage of Days Abstinent | 14 Percentage of days abstinent | Standard Deviation 23 |
Primary
Percent Heavy Drinking Days
Change in percent heavy drinking days (number of days of \> 4 drinks/day divided by number of days in that study period).
Time frame: baseline to 12 weeks or endpoint (up to 11 weeks)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine + Placebo | Percent Heavy Drinking Days | -10 Percent heavy drinking days | Standard Deviation 19 |
| Quetiapine + Topiramate | Percent Heavy Drinking Days | -14 Percent heavy drinking days | Standard Deviation 25 |