Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults
Condition: Bipolar Disorder; Alcohol Abuse
MeSH terms: Alcoholism; Bipolar Disorder
Intervention: quetiapine and placebo; Quetiapine and Topiramate
Intervention description: 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.
Intervention MeSH terms: Topiramate; Quetiapine Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 56.0
Sex: All
Minimum age: 12 Years
Maximum age: 25 Years
Healthy volunteers: No
Keywords: Adolescents

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.
    

Eligibility criteria:

        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.