Allopurinol Maintenance Study for Bipolar Disorder

The purpose of this study is to investigate the efficacy of allopurinol as an augmentation
agent for the prevention of mania in bipolar disorder patients with currently stable mood.
Bipolar disorder is a mental disorder with severe mood swings (mania and depression). Despite
the development of medications for mania, they may have significant side effects, high costs
and the need for serum level monitoring. These factors adversely affect medication compliance
in bipolar patients. One recent study indicated the efficacy of allopurinol in the treatment
of bipolar mania. Our hypothesis is that the addition of allopurinol to standard medications
for bipolar disorder will decrease the recurrences of manic episodes compared to standard
medications.

This study will recruit bipolar disorder patients currently mood stable on a therapeutic dose
of an anti-manic medication. Stable mood will be defined as a Young Mania Rating Scale score
≤10 and Hamilton Depression Rating Scale ≤10. Subjects must have a diagnosis of bipolar
disorder confirmed by the Mini International Neuropsychiatric Interview (MINI). YMRS and MINI
are common research questionnaires used in bipolar disorder studies. Potential subjects will
be identified and approached during an outpatient clinical visit by a member of the research
team and identified by their treating physicians and referred to the researchers.

This study involves adding allopurinol to subjects' current bipolar medications. This study
will be a open label, naturalistic study. The subject will be examined monthly for manic
symptoms for 2 years. Semi-structured interviews and study questionnaires will be
administered to subjects at each visit. Monthly Follow-up Study Visits (once per month for 2
years - Months 1-5, 7-11, 13-17, 19-23) may be conducted either in-person or over the phone.
All of the questionnaires will be administered by a clinician if the visit is completed over
the phone. However, the 6-month interval visits (Months 6, 12, 18, and 24) must be done at
the research center.

The primary outcome measure will be the number of manic episodes in the 2 year study period.
We will also measure the changes in medication doses that subjects in each group need to
maintain mood stability.

Inclusion Criteria:

1. Subjects must be between ages 18 and 70.

2. Subjects must meet DSM-IV criteria for bipolar disorder confirmed by the Mini
International Neuropsychiatric Interview (MINI).

3. Subjects must be taking at least one medication for mania at a therapeutic dose for at
least 2 weeks.

4. Subjects must have been diagnosed with bipolar disorder, type 1, for at least 2 years
prior to baseline.

5. Subjects must have adequate response to medications as evidenced by Young Mania Rating
Scale (YMRS) score less than or equal to 10 at screening and at baseline.

6. Subjects must have adequate response to medications as evidenced by Hamilton
Depression Rating Scale (HAM-D) score less than or equal to 10 at screening and at
baseline.

7. Subjects must have had at least 1 manic episode in the 2 year period prior to entering
the study.

8. Female subjects must be either postmenopausal for at least 1 year, surgically sterile,
abstinent or practicing an effective method of birth control if sexually active.
Acceptable methods of birth control during this study are regular use of contraceptive
pills, intra-uterine devices, barrier methods or abstinence. Female subjects must also
have a negative urine pregnancy test at screening, baseline and other time points
throughout the study.

9. Subjects must be able and willing to comply with self-administration of medication or
have consistent help/support available.

10. Subjects must have signed an informed consent document indicating that they understand
the purpose of and procedures required for the study and are willing to participate in
the study.

11. Subjects must be able and willing to meet or perform study requirements (e.g. answer
self-administered questionnaires).

12. Subjects must be willing to allow study staff to contact subject's regular
psychiatrist while the subject is in the study.

Exclusion Criteria:

1. Subjects who are unable to provide informed consent.

2. Subjects with a serious, unstable medical illness (such as cardiovascular,
respiratory, neurologic, hematologic, renal, hepatic, endocrine, immunologic, or other
systemic illness), a history of cerebrovascular disease, uncontrolled diabetes
mellitus or AIDS. Subjects with chronic illness must be stable and otherwise
physically healthy on the basis of a physical examination, medical history,
electrocardiogram and the results of blood biochemistry, hematology tests and a
urinalysis.

3. Subjects who develop a medical condition during participation which can affect mood
stability (i.e. seizure disorder, brain tumors, brain trauma, stroke, multiple
sclerosis, etc.)

4. Subjects who develop substance abuse or dependence during participation in the study.

5. Subjects taking azathioprine, mercaptopurine, apalcillin, and/or amoxicillin.

6. Subjects who have been intoxicated with alcohol or drugs within the last 72hrs.

7. Subjects with a history of severe pre-existing gastrointestinal narrowing or inability
to swallow oral study medication whole with the aid of water.

8. Female subjects who are pregnant or nursing.

9. Subjects who have previously participated in this study.

10. Subjects with an anticipated life expectancy of 6 months or less.

11. Subjects who have received an experimental drug or used an experimental medical device
within 1 month of screening.