Buprenorphine for Treatment Resistant Depression (BUP-TRD)
|Depression Depressive Disorder Depressive Disorder, Major||Drug: Buprenorphine Drug: Placebo||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Buprenorphine For Treatment Resistant Depression|
- Montgomery Asberg Depression Rating Scale [ Time Frame: 6 weeks ]measure of depression severity Theoretical Range 0-60 lower values represent better outcome
- Blood Pressure [ Time Frame: 6 weeks ]Measure of systolic and diastolic blood pressure. 140/90 or lower is considered normal and indicates a better outcome.
- UKU Side Effect Rating Scale [ Time Frame: 6 weeks ]measure of side effects 46 items with scores of 0,1,2,3 possible. Theoretical range 0-138 Lower scores indicate fewer side effects
- Heart Rate [ Time Frame: 6 weeks ]Heart Rate (Beats per minute) 60-100 beats per minute is considered normal lower heart rate represent healthier outcome
- Weight [ Time Frame: 6 weeks ]Participant weight
- Brief Symptom Inventory -- Anxiety Subscale [ Time Frame: 6 weeks ]measure of anxiety Lower numbers indicate better outcome Theoretical Range 0-2.4
- Positive and Negative Affect Scale [ Time Frame: 6 weeks ]
Positive Affect Score: Scores can range from 10 - 50, with higher scores representing higher levels of positive affect.
Negative Affect Score: Scores can range from 10 - 50, with lower scores representing lower levels of negative affect.
|Study Start Date:||September 2011|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
0.2 to 1.6mg of buprenorphine sublingual over the course of 8 weeks
low-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day)
Placebo Comparator: Placebo
matching placebo- sublingual- over the course of 8 weeks
Rates of treatment resistant depression (TRD) in randomized controlled trials range from 50-80% using SSRIs and SNRIs. Innovative treatments are sorely needed. Modulation of the opiate system may be a novel treatment approach for TRD. Buprenorphine (BUP) is a partial agonist at mu-receptors, and also displays affinity for kappa and delta receptors. BUP has a favorable safety profile with low risk of respiratory depression, and the pharmacokinetics are not affected by advanced age or renal dysfunction. This combination of mu-agonism and kappa-antagonism produces less dysphoria than methadone, and animal studies suggest that kappa-antagonism may exert antidepressant effects. In this small proof of concept RCT (n=20), the investigators hypothesize that there will be differences between the group receiving buprenorphine and the group receiving placebo for the following: 1) depression, anxiety, and sleep, and 2)activation of the limbic system and brain structures rich in opiate receptors and critical to reward circuits. In addition, the investigators hypothesize that there will not be differences for measures of safety (vital signs, measures of memory and reaction time, and falls) between the two groups. This pilot project will provide compelling preliminary data to support a R01 application to test the efficacy of buprenorphine for these therapeutically challenging patients.
- Describe the relative safety of BUP in adults with TRD. The investigators hypothesize that there will be no differences in vital signs, measures of memory and reaction time, or falls between the two groups.
- Describe the clinical effect of BUP in adults with TRD. The investigators hypothesize that depression, anxiety, sleep, and health-related quality of life, will improve to a greater extent among those receiving BUP.
- Characterize the change in the phMRI responses to buprenorphine compared to placebo. The investigators will compare activation of the limbic system (rACC, insula, and amygdala) and brain structures rich in opiate receptors (periaqueductal grey) and critical to reward circuits (nucleus accumbens) before and immediately after administration of BUP or placebo.
The investigators are recruiting 20 community-dwelling adults, age 21 and older, who have tried at least two FDA-approved antidepressant medications at therapeutic doses each for at least 6 weeks during this episode of depression, and are still depressed.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01407575
|United States, Pennsylvania|
|Western Psychiatric Institute and Clinic, University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||Jordan F Karp, M.D.||University of Pittsburgh|