The purpose of this study is to investigate the efficacy of allopurinol as an augmentation
agent for treatment resistant mania and mixed mania.
Bipolar disorder is a severe mental disorder with episodes of mania and depression. Current
medications for mania can have significant side effects, high costs and the need for blood
monitoring. The purpose of this research study is to study the effectiveness of
allopurinol, in combination with lithium or valproic acid or carbamazepine, for
treatment-resistant bipolar mania and mixed mania. This research study is designed to test
the safety and/or effectiveness of allopurinol that has been approved by the U.S. Food and
Drug Administration (FDA) for recurrent calcium renal calculus, gout, hyperuricemia (cancer
and tumor lysis syndrome), but it is not approved for use in treatment-resistant bipolar
mania or mixed mania.
Participants in this double-blind study will be randomly assigned to one of two study
groups. The first group will receive the study medication of allopurinol while the second
group will receive a placebo. These will be taken in conjunction with current medications
and doses. The study will last for 7 weeks (an initial screening, a baseline visit and 4
follow-up visits at weeks 1,2,4, and 6). The initial screening visit will be used to
determine whether or not the subject is able to participate in the study. The following will
be conducted during the screening visit: Review of medical and psychiatric history along
with standard psychiatric assessment exams; Physical examination, including review of prior
and current medications and adverse drug effects; An electrocardiogram (ECG) - a painless
test which is done by attaching straps or pads to your limbs and chest and recording the
electrical pattern of your heart, will be done to record your heart rhythm; About 5
tablespoons of blood will be drawn to assess basic laboratory values that show if you are
healthy enough to participate in the study; Blood levels of lithium, valproic acid, and/or
carbamazepine will be measured; A urine sample will be collected to test for the presence of
illegal drugs and for pregnancy test (if you are a female of child-bearing potential);
Collection of demographic data (e.g., age, gender, marital status, social and vocational
status) and other information including health beliefs, and knowledge of illness. At the
baseline visit the participant will be given questionnaires related to mood, quality of
life, disability, medications, and side effects. The participant's vitals (temperature,
weight, heart rate, and blood pressure) will be measured. The participant will be randomized
to treatment (300 mg of allopurinol/day) or placebo. After week one at the Week 1 visit,
those that have tolerated the dosage of allopurinol will get an increased dosage. The
participant will also complete a set of questionnaires. Vitals will be taken. The remaining
follow-up visits will be similar to visit one except that there will be no more increases in
dosage; Week 2 will include a blood draw to measure levels of lithium, valproic acid, and/or
carbamazepine in the participant's blood, and the final visit at Week 6 will in addition
include a blood draw, and exit physical exam, and a urine sample will be collected.
- Subjects must be between ages 18 and 70.
- Subjects must meet DSM-IV criteria for bipolar disorder, most recent episode manic or
mixed, at the time of screening confirmed by the Mini International Neuropsychiatric
- Subjects must be taking at least one medication for mania (lithium, valproic acid,
carbamazepine) at a therapeutic dose for at least 4 weeks.
- Subjects must have non-response or partial response to medications as evidenced by
Young Mania Rating Scale (YMRS) score greater than or equal to 14 at screening and at
- 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. Female subjects must also have a negative urine pregnancy test at screening,
baseline and other time points throughout the study.
- Subjects must be able and willing to comply with self-administration of medication or
have consistent help/support available.
- 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.
- Subjects must be able and willing to meet or perform study requirements (e.g. answer
- Subjects must be willing to allow study staff to contact subject's regular
psychiatrist while the subject is in the study.
- Subjects who are unable to provide informed consent.
- 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
- Subjects with a history of substance abuse or dependence (excluding nicotine and
caffeine) according to DSM-IV criteria within last 4 weeks.
- Subjects taking azathioprine, mercaptopurine, apalcillin, and/or amoxicillin.
- Subjects taking dopamine agonists and/or anti-psychotics.
- Subjects who have been intoxicated with alcohol or illicit drugs within 3 days prior
- Subjects with a history of severe pre-existing gastrointestinal narrowing or
inability to swallow oral study medication whole with the aid of water.
- Female subjects who are pregnant or nursing.
- Subjects who have previously participated in this study.
- Subjects with an anticipated life expectancy of 6 months or less.
- Subjects who have received an experimental drug or used an experimental medical
device within 1 month of screening.