Buprenorphine Used With Treatment Resistant Depression in Older Adults

NCT02181231 | Completed Phase 1 Results DMC

• 3 other identifiers: 201406016IND 123020IND 130774
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder; Depression

Keywords

depression; older adult; buprenorphine; Effexor XR; treatment resistant; venlafaxine; Saint Louis; late life; major depression

Outcome Measures

Primary Outcomes (3)

• Montgomery-Asberg Depression Rating Scale (MADRS)

  Measure of depression severity, range of 0-60, with higher scores indicating more severe depression. We calculated the mean change in depression for both groups using baseline MADRS and week 8 MADRS scores.

  Baseline and 8 weeks

• Frequency, Intensity, and Burden of Side Effects Rating (FIBSER)

  Three item side effect scale used to assess frequency and intensity of side effects (range 0-6 for each item). We calculated the total score of all three items (range 0-18) with lower numbers indicating less frequency. We calculated the mean score at baseline and week 8 (final timepoint).

  Week 1 and week 8

• Antidepressant Side Effect Checklist (ASEC)

  Measure of side effects, consisting of 21 items, ranging from 0-3 (0 indicates no side effect, 3 indicates severe side effect). We calculated the total final score for the 21 items (total range is 0-63). A higher total number represents a greater severity in reported side effects. We calculated the mean change in side effects for both groups using baseline and 8 week data.

  Baseline and 8 weeks

Secondary Outcomes (3)

• Suicide Ideation Scale (SIS)

  Baseline and 8 weeks

• Brief Symptom Inventory-Anxiety Subscale (BSI)

  Baseline and 8 weeks

• Numeric Scale of Pain (NRS-P)

  Baseline and 8 weeks

Study Arms (2)

venlafaxine plus buprenorphine

EXPERIMENTAL

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.

Drug: venlafaxine XR; Drug: buprenorphine

venlafaxine XR plus placebo

PLACEBO COMPARATOR

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.

Drug: venlafaxine XR; Drug: Placebo

Interventions

venlafaxine XR DRUG

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

Also known as: Effexor XR

venlafaxine XR plus placebo; venlafaxine plus buprenorphine

buprenorphine DRUG

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

Also known as: Temgesic, Subutex, Suboxone

venlafaxine plus buprenorphine

Placebo 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.

venlafaxine XR plus placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> or = to 50 years.
• 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).
• Montgomery Asberg Depression Rating Scale (MADRS) \>/= to 15.
• Has or agrees to establish a clinical relationship with primary care physician (PCP).
• Availability of an informant (e.g., emergency contact).

You may not qualify if:

• Inability to provide informed consent.
• Depressive symptoms not severe enough (i.e., MADRS \< 15) at the baseline assessments
• 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).
• Lifetime diagnosis of bipolar I or II disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, or current psychotic symptoms, as diagnosed by the SCID.
• Abuse of or dependence on alcohol or other substances within the past 3 months as determined by SCID, and confirmed by study physician interview.
• Drinking 15 or more drinks per week or consuming 5 or more drinks on any one occasion in the past week.
• 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.
• 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).
• 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).
• Non-correctable clinically significant sensory impairment (i.e., cannot hear well enough to cooperate with interview).
• 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.
• 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).
• History of opioid abuse or dependence.
• Severe pain, defined as \> 7 on 0-10 numeric rating scale for pain.
• Concomitant use of strong or moderate CYP3A4 inhibitor (indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Reckitt Benckiser LLC: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Venlafaxine Hydrochloride; Buprenorphine; Buprenorphine, Naloxone Drug Combination

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Phenethylamines; Ethylamines; Amines; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Lipids; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Naloxone; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Eric Lenze
• Organization: Washington University School of Medicine

lenzee@wustl.edu

314-362-1671

Study Officials

• Eric J Lenze, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: July 1, 2014
• First Posted: July 3, 2014
• Study Start: June 1, 2016
• Primary Completion: April 30, 2018
• Study Completion: April 30, 2018
• Last Updated: June 4, 2019
• Results First Posted: June 4, 2019

Record last verified: 2019-06

Locations

US (1)