Efficacy and Tolerability of Topiramate in Treatment of Bipolar Mania and Alcohol Use in Adolescents and Young Adults

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.