Buprenorphine for Treatment Resistant Depression (BUP-TRD)
The purpose of this study is to compare the safety and efficacy of buprenorphine with placebo for adults with treatment resistant depression (TRD).
Depressive Disorder, Major
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Buprenorphine For Treatment Resistant Depression|
- Montgomery Asberg Depression Rating Scale [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Vital signs, falls, changes in attention and memory [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
- UKU Side Effect Rating Scale [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
- Brief Symptom Inventory -- Anxiety Subscale [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Pain Numeric Rating Scale (20 item) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Positive and Negative Affect Scale [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||September 2011|
|Estimated Study Completion Date:||August 2013|
|Estimated Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
low-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day)
|Placebo Comparator: Placebo||
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.
|United States, Pennsylvania|
|Western Psychiatric Institute and Clinic, University of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15213|
|Contact: Crystal Spotts 412-246-5764 firstname.lastname@example.org|
|Contact: Luann Shutt, RN 412-246-6111 email@example.com|
|Principal Investigator: Jordan F Karp, M.D.|
|Principal Investigator:||Jordan F Karp, M.D.||University of Pittsburgh|