Clinical Trial of Pramipexole in Bipolar Depression

• Status: Completed
• Trial end date: 2005-11-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to examine the safety and effectiveness of the drug pramipexole given in combination with lithium or divalproex for the short-term treatment of acute depression in patients with bipolar disorder.

Bipolar disorder is a severe, chronic, and often life-threatening illness. Treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, a significant proportion of depressed patients fail to respond to first-line antidepressant treatment. Novel and improved therapeutics for bipolar depression are needed. This study will evaluate the antidepressant properties of pramipexole.

This study will be conducted in three phases. Phase 1 is a 14-day washout period in which participants will be tapered off all their psychiatric medicines except divalproex or lithium. Participants will also be asked to adhere to a low caffeine and low monoamine diet. During Phase 2, participants will be randomly assigned to receive either pramipexole or placebo (an inactive pill) for 6 weeks. Participants who respond to treatment will be given either open-label pramipexole or another clinical treatment.

Participants will be screened with a medical history, physical examination, electrocardiogram (EKG), blood and urine tests, and a psychiatric evaluation. Women of childbearing potential will have a pregnancy test. Participants will have a physical exam and EKG at study entry and study completion. Blood will be drawn at various times throughout the study. Pulse and blood pressure measurements will be taken daily. Weekly interviews will be conducted. Participants and a control group of healthy volunteers will undergo positron emission tomography (PET) and magnetic resonance imaging (MRI) scans of the brain.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: National Institute of Mental Health (NIMH)
• Treatments: Antidepressive Agents; Pramipexole

Criteria

INCLUSION CRITERIA:

Male or female subjects, 18 to 70 years of age.

Female subjects of childbearing potential must be using a medically accepted means of contraception.

Each subject must understand the nature of the study and must sign an informed consent document.

Subjects must fulfill the criteria for Bipolar II disorder depressed without psychotic features as defined in DSM-IV (296.89) based on clinical assessment and confirmed by structured diagnostic interview SCID-P.

Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.

Subjects must have experienced, in the opinion of the investigator, at least two previous hypomanic and two major depressive episodes as defined in DSM-IV.

Subjects must have failed to respond in the past to an adequate dose and duration of at least one antidepressant (SSRI, bupropion, or venlafaxine) during an episode of major depression.

Subjects must take VPA or lithium (valproate 50-125 microg/ml or lithium 0.6-1.2 mEq/L) for at least 4 weeks prior to Visit 2. At least two blood levels of lithium and VPA must be within therapeutic range (each at least 1 week apart) prior to Visit 2. If the subject is not taking lithium or VPA, the research physician may start them on lithium or VPA at the NIH.

Current major depressive episode no more than 24 months.

EXCLUSION CRITERIA:

Presence of psychotic features

Participating in a clinical trial of another investigational drug within 1 month prior to study entry (Visit 1).

Female subjects who are either pregnant or nursing.

Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.

Subjects with uncorrected hypothyroidism or hyperthyroidism.

Subjects with one or more seizures without a clear and resolved etiology.

Documented history of hypersensitivity or intolerance to pramipexole

DSM-IV substance abuse (except nicotine and caffeine) within the past 90 days and substance dependence within the past 5 years.

Subjects with a DSM-IV rapid cycling course of illness in the past 12-months.

Treatment with an injectable depot neuroleptic within less than one dosing interval prior to Visit 2.

Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week prior to Visit 2.

Treatment with fluoxetine within 4 weeks prior to Visit 2.

Treatment with any other concomitant medication (Appendix B) 1 day prior to Visit 2.

Treatment with clozapine or ECT within 3 months prior to Visit 2.

Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.

Judged clinically to be at serious suicidal risk.

Patients will not be allowed to receive structured psychotherapy during the trial.