Buprenorphine for Treatment Resistant Depression (BUP-TRD)

This study has been completed.
Sponsor:
Collaborator:
National Alliance for Research on Schizophrenia and Depression
Information provided by (Responsible Party):
University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT01407575
First received: July 29, 2011
Last updated: January 17, 2014
Last verified: January 2014
  Purpose

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


Condition Intervention Phase
Depression
Depressive Disorder
Depressive Disorder, Major
Drug: Buprenorphine
Drug: Placebo
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 20
Study Start Date: September 2011
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Buprenorphine Drug: Buprenorphine
low-dose buprenorphine (range 0.2 mg/day -- 1.6 mg/day)
Other Names:
  • suboxone
  • buprenex
  • temgesic
  • subutex
Placebo Comparator: Placebo Drug: Placebo
matched placebo

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.

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01407575

Locations
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
Investigators
Principal Investigator: Jordan F Karp, M.D. University of Pittsburgh
  More Information

No publications provided

Responsible Party: University of Pittsburgh
ClinicalTrials.gov Identifier: NCT01407575     History of Changes
Other Study ID Numbers: BUP-TRD
Study First Received: July 29, 2011
Last Updated: January 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
Buprenorphine
Receptors, opioid
Receptors, opioid, kappa

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

ClinicalTrials.gov processed this record on September 18, 2014