Buprenorphine for Treatment Resistant Depression (BUP-TRD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01407575
Recruitment Status : Completed
First Posted : August 2, 2011
Results First Posted : March 17, 2016
Last Update Posted : March 9, 2018
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
Jordan F. Karp, University of Pittsburgh

Brief Summary:
The purpose of this study is to compare the safety and efficacy of buprenorphine with placebo for adults with treatment resistant depression (TRD).

Condition or disease Intervention/treatment Phase
Depression Depressive Disorder Depressive Disorder, Major Drug: Buprenorphine Drug: Placebo Phase 3

Detailed Description:

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.

Specific Aims:

  1. 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.
  2. 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.
  3. 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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 13 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Buprenorphine For Treatment Resistant Depression
Study Start Date : September 2011
Actual Primary Completion Date : August 2013
Actual Study Completion Date : August 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Buprenorphine
0.2 to 1.6mg of buprenorphine sublingual over the course of 8 weeks
Drug: Buprenorphine
low-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day)
Other Names:
  • suboxone
  • buprenex
  • temgesic
  • subutex

Placebo Comparator: Placebo
matching placebo- sublingual- over the course of 8 weeks
Drug: Placebo
matched placebo

Primary Outcome Measures :
  1. Montgomery Asberg Depression Rating Scale [ Time Frame: 6 weeks ]
    measure of depression severity Theoretical Range 0-60 lower values represent better outcome

  2. 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.

  3. 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

  4. 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

  5. Weight [ Time Frame: 6 weeks ]
    Participant weight

Secondary Outcome Measures :
  1. Brief Symptom Inventory -- Anxiety Subscale [ Time Frame: 6 weeks ]
    measure of anxiety Lower numbers indicate better outcome Theoretical Range 0-2.4

  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 21 and older
  • Major depressive disorder
  • Non-responder to at least 2 FDA-approved antidepressants prescribed at a therapeutic dose, each for at least 6 weeks, or is a depression non-responder from an ongoing study of late-life depression at our research clinic.
  • For women of child-bearing age, must have negative pregnancy test and agree not to get pregnant while participating.

Exclusion Criteria:

  • Concomitant use of strong or moderate CYP3A4 inhibitor.
  • Refusal to stop all opioids.
  • Refusal to discontinue all alcohol.
  • Refusal to discontinue benzodiazepines other than the equivalent of lorazepam 2 mg/day prescribed at a stable dose for at least the past 2 weeks.
  • Hepatic impairment (AST/ALT > 1.5 times upper normal).
  • Lung disease requiring supplemental oxygen (CPAP for sleep apnea is acceptable).
  • Estimated creatinine clearance <30 mL/min.
  • Inability to provide informed consent.
  • Depressive symptoms not severe enough (i.e., MADRS < 10) at the baseline assessment.
  • Dementia, as defined by MMSE < 24 and clinical evidence of dementia
  • Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms.
  • Abuse of or dependence on alcohol or other substances within the past 3 months.
  • Meets criteria for history of abuse or dependence upon opioids.
  • High risk for suicide.
  • Contraindication to buprenorphine.
  • Inability to communicate in English.
  • Non-correctable clinically significant sensory impairment.
  • Unstable medical illness.
  • Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01407575

United States, Pennsylvania
Western Psychiatric Institute and Clinic, University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Alliance for Research on Schizophrenia and Depression
Principal Investigator: Jordan F Karp, M.D. University of Pittsburgh

Responsible Party: Jordan F. Karp, MD, University of Pittsburgh Identifier: NCT01407575     History of Changes
Other Study ID Numbers: BUP-TRD
First Posted: August 2, 2011    Key Record Dates
Results First Posted: March 17, 2016
Last Update Posted: March 9, 2018
Last Verified: February 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Jordan F. Karp, University of Pittsburgh:
Receptors, opioid
Receptors, opioid, kappa

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Treatment-Resistant
Depressive Disorder, Major
Pathologic Processes
Behavioral Symptoms
Mood Disorders
Mental Disorders
Analgesics, Opioid
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Narcotic Antagonists