Buprenorphine Used With Treatment Resistant Depression in Older Adults

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

18 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-01

Study Completion Date

2018-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The investigators are conducting a research study to learn about the safety and benefit of using a medication called buprenorphine for patients with difficult to treat depression. This research study is testing whether combining two medications will be effective in treating depression when initial treatment with just one antidepressant does not relieve the depressive symptoms; this is what is called "difficult to treat depression" or "treatment resistant depression". The two medications the investigators are using are: an anti-depressant medication called venlafaxine extended release (venlafaxine XR), which is the generic form of Effexor, and buprenorphine. Buprenorphine is a medication that is FDA approved for the treatment of opioid dependence. The investigators are testing whether adding buprenorphine to venlafaxine XR enhances treatment response.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Incomplete Response in Late-Life Depression: Getting to Remission With Buprenorphine

NCT02263248

Major Depressive Disorder Depression

COMPLETED PHASE1/PHASE2

Buprenorphine for Late-Life Treatment Resistant Depression

NCT01071538

Depression

COMPLETED PHASE2

Buprenorphine for Treatment Resistant Depression

NCT01407575

Depression Depressive Disorder Depressive Disorder, Major

COMPLETED PHASE3

Effects of Buprenorphine on Mood in Adults With a Range of Depressive Symptomatology

NCT02659787

Depression

COMPLETED NA

The Safety and Efficacy of the Buprenorphine Transdermal Delivery System in Subjects With Chronic Back Pain.

NCT00315887

Chronic Low Back Pain

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

We will consent approximately 100 participants, aged 50 and older, of both sexes and all races. Participation may last up to 32 weeks. We will utilize a clinical trial that has 3 Phases. In Phase 1 we will treat participants with an approximate 12 week course of open-label venlafaxine XR. This is the same lead-in treatment as in our ongoing "IRL Grey" ("Incomplete Response in Late Life Depression: Getting to Remission") multi-site R01 for late-life treatment resistant depression (LL-TRD), and we have found it to be highly successful. Participants who find relief from their depressive symptoms on venlafaxine XR alone will exit the study. Participants meeting criteria for an incomplete response (those still feeling depressed or withdrawn), will be randomly assigned to receive either low-dose buprenorphine or placebo augmentation of venlafaxine xr for 8 weeks (Phase 2), with the goal of achieving remission. Subjects will start at 0.2mg and titrate up as needed to 1.2mg. Subjects may undergo up to 2 MRI scans at the beginning and end of Phase 2 as well as cognitive testing at the same time points. At the conclusion of Phase 2, the blind will be broken for all participants. The participants who were on placebo will be able to begin taking buprenorphine immediately for Phase 3 (approximately 8 weeks). The participants who were already on buprenorphine in Phase 2 can continue to take it during Phase 3. Buprenorphine (BPN) will be tapered upon exiting the study, under the guidance of the P.I. The Phase 3 variations will allow all participants a chance to experience the benefits of buprenorphine (BPN). Efficacy and tolerability data will provide a clinically informative estimate of benefits and risks of buprenorphine augmentation for late-life treatment resistant depression (LL-TRD). We will randomize approximately 20 subjects into Phase 2. Additionally, we will collect buprenorphine (BPN) plasma levels on all those randomized to explore a dose-effect relationship on treatment response.

A small pilot study (ages 21 and up) of up to 15 healthy control subjects will be studied over an approximate 2 week period in order to ensure all of our procedures are working and to determine that there are clinical effects from buprenorphine. Control subjects will undergo a baseline PET/MRI before taking buprenorphine. At least 24 hours after the imaging, control subjects will receive a small dose of BPN starting at 0.2 mg/day and will titrate up as tolerated to 1.2 mg/day for the first week. Each subject will remain at approximately 1.2 mg/day for the duration of the study. At the end of the study, subjects will undergo a second PET/MRI.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Major Depressive Disorder Depression

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

venlafaxine plus buprenorphine

Drug: venlafaxine XR plus buprenorphine Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks. 2 MRI sessions may occur before and during randomization.

Group Type EXPERIMENTAL

venlafaxine XR

Intervention Type DRUG

slow titration up to maximum dose of 300mg per day, will remain on venlafaxine XR for up to 32 weeks

buprenorphine

Intervention Type DRUG

randomized to either buprenorphine or placebo, dose range from 0.2 mg/ qd to 2mg/ qd

venlafaxine XR plus placebo

Drug: venlafaxine XR plus placebo Dosage varies. Subject remains on antidepressant throughout the 32 week study. Will be randomized to buprenorphine or placebo for up to 16 weeks. 2 MRI sessions may occur before and during randomization.

Group Type PLACEBO_COMPARATOR

venlafaxine XR

Intervention Type DRUG

slow titration up to maximum dose of 300mg per day, will remain on venlafaxine XR for up to 32 weeks

Placebo

Intervention Type DRUG

patients will remain on venlafaxine XR and be randomized to receive either placebo or buprenorphine for 8 weeks. at the end of the 8 weeks those who did not receive buprenorphine will be offered the opportunity to try it.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

venlafaxine XR

slow titration up to maximum dose of 300mg per day, will remain on venlafaxine XR for up to 32 weeks

Intervention Type DRUG

buprenorphine

randomized to either buprenorphine or placebo, dose range from 0.2 mg/ qd to 2mg/ qd

Intervention Type DRUG

Placebo

patients will remain on venlafaxine XR and be randomized to receive either placebo or buprenorphine for 8 weeks. at the end of the 8 weeks those who did not receive buprenorphine will be offered the opportunity to try it.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Effexor XR Temgesic Subutex Suboxone

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Age \> or = to 50 years.
2. Major depressive disorder (MDD), single or recurrent, as diagnosed by the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID-IV).
3. Montgomery Asberg Depression Rating Scale (MADRS) \>/= to 15.
4. Has or agrees to establish a clinical relationship with primary care physician (PCP).
5. Availability of an informant (e.g., emergency contact).

Exclusion Criteria

1. Inability to provide informed consent.
2. Depressive symptoms not severe enough (i.e., MADRS \< 15) at the baseline assessments
3. Dementia, as defined by Mini Mental State Exam (3MS) \< 84 and clinical evidence of dementia (e.g., memory impairment, executive dysfunction, agnosia, apraxia, aphasia, with functional impairment).
4. Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID.
5. Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.
6. Drinking 15 or more drinks per week or consuming 5 or more drinks on any one occasion in the past week.
7. High risk for suicide (e.g., active SI and/or current/recent intent or plan) and unable to be managed safely in the clinical trial (e.g., unwilling to be hospitalized). Urgent psychiatric referral will be made in these cases.
8. Contraindication to venlafaxine XR or BPN as determined by PCP and study physician including history of intolerance of either venlafaxine XR or BPN in the study target dosage range (venlafaxine XR at up to 300 mg/day; BPN at up to 2 mg/day).
9. Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English).
10. Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
11. Unstable medical illness, including delirium, uncontrolled diabetes mellitus, hypertension, hyperlipidemia, or cerebrovascular or cardiovascular risk factors that are not under medical management. This will be determined based on information from the patient's personal physician and study physician's clinical judgment. Referral to the patient's personal physician or to a general practitioner will be made in these cases.
12. Subjects taking psychotropic medications that cannot be safely tapered and discontinued prior to study initiation. The following exceptions are allowed if they have been taken at a stable dose for at least 4 weeks prior to study entry and there is not a plan to change the dose during the next 28 weeks: benzodiazepines up to 2 mg/d lorazepam equivalent; other sedative-hypnotics (e.g., zolpidem, zaleplon, eszopiclone); gabapentin if prescribed for non-psychiatric indication (e.g., neuropathy).
13. History of opioid abuse or dependence.
14. Severe pain, defined as \> 7 on 0-10 numeric rating scale for pain.
15. Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem).
16. Refusal to stop all opioids (to avoid precipitating opioid withdrawal).
17. Hepatic impairment
18. Estimated Glomerular Filtration Rate (GFR) \< 20 ml/min.
19. Inability/refusal to identify a person as an emergency contact.
20. Pregnancy

Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No