Conditions: Bipolar Disorder Mixed Mania Treatment-Resistant Mania
Keywords: Bipolar Disorder Mania Mixed mania Allopurinol Treatment-Resistant mania
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 40
Healthy volunteers: no

Brief summary:
The purpose of this study is to investigate the efficacy of allopurinol as an augmentation agent for treatment resistant mania and mixed mania.

Detailed description:
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.

Arms:
arm 1: Subjects will be randomized to allopurinol at a fixed dose of 300 mg/day for the first week and then 600mg/day while continuing their current medications during the 7-week study. A battery of assessments will be administered at baseline and weeks 1, 2, 4, 6 after baseline. At each assessment, subjects will also be asked about side effects including potential side effects of allopurinol. Side effects will be assessed by the Treatment Emergent Side Effects Scale. Serum levels of lithium, valproic acid, carbamazepine, atypical antipsychotics or atypical antipsychotic metabolite, uric acid blood levels will be drawn at screen and at week 6 after baseline. Subjects taking only lithium, valproic acid, and/or carbamazepine will also have their serum levels drawn at week 2. arm 2: Subjects will be randomized to placebo and will follow the same protocol as the allopurinol group.

Interventions: intervention 1: Allopurinol intervention 2: Placebo
Intervention descriptions: intervention 1: 300-600 mg/day over a 6 week period intervention 2: Inactive substance

Protocol document: