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

NCT02263248 | Completed Phase 1 DMC

• 1 other identifier: 035/2014
• Study Type: interventional
• Target: 56
• 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 patient 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 medication the investigators are using are " an anti-depressant medication called venlafaxine XR ( 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 enhances treatment response.

Conditions

Major Depressive Disorder; Depression

Outcome Measures

Primary Outcomes (1)

• The Montgomery-Asberg Depression Rating Scale

  MADRS at baseline will establish study eligibility and will assess treatment-sensitive change in MDD.

  32 weeks

Secondary Outcomes (5)

• Suicidal Ideation Scale ( SIS)

  32 weeks

• Brief Symptom Inventory for Anxiety

  32 weeks

• Numeric Scale of Pain ( NRS-P)

  16 weeks

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

  16 weeks

• Antidepressant Side Effect Checklist (ASEC)

  16 weeks

Study Arms (2)

venlafaxine XR plus buprenorphine

EXPERIMENTAL

Drug Intervention: 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.

Drug: venlafaxine; Drug: buprenorphine

venlafaxine XR plus placebo

PLACEBO COMPARATOR

Drug Intervention: venlafaxine XR plus placebo Dosage varies . Subject remains on antidepressant throughout the 32 weeks study. Will be randomized to buprenorphine or placebo for up to 16 weeks

Drug: venlafaxine; Drug: placebo

Interventions

venlafaxine DRUG

slow titration to a maximum of 300 mg per day. will remain on venlafaxine XR for upto 32 weeks.

Also known as: Effexor

venlafaxine XR plus buprenorphine; venlafaxine XR plus placebo

buprenorphine DRUG

randomized to either buprenorphine or placebo, dose range from 0.2 mg qd/ to 1.2 mg qd

Also known as: Temgesic, Subutex, Suboxone

venlafaxine XR plus buprenorphine

placebo DRUG

patients will remain on venlafaxine XR and be randomzied to receive either placebo or buprenorphine for 8 weeks. at the end of 8 weeks those who did not receive buprenorphine will be given an 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 \> 50 years
• Major depressive disorder (MDD), single or recurrent, as diagnosed by the SCID-IV (or SCID-5 if available)
• MADRS \> 15
• Has or agrees to establish a clinical relationship with primary care physician (PCP).
• Availability of an informant (e.g., emergency contact) is encouraged but not required for study participation

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 3MS \< 80 and clinical evidence of dementia
• 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 score of \> 8 on AUDIT-C and confirmed by study physician interview
• 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 or buprenorphine as determined by PCP and study physician including history of intolerance of either venlafaxine or buprenorphine in the study target dosage range (venlafaxine at up to 300 mg/day; buprenorphine at up to 1.2 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 32 -36 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 opiate 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, ketonazole, nefazodone, saquinovir, telithromycin, aprepitant, erythromycin, fluconazole, grapefruit juice, verapamil, diltiazem)
• Refusal to stop all opioids (to avoid precipitating opioid withdrawal)

Sponsors & Collaborators

• Centre for Addiction and Mental Health: lead
• Reckitt Benckiser LLC: collaborator

Study Sites (1)

Centre for Addiction and Mental Health

Toronto, Ontario, M6J1H4, Canada

Location

Related Publications (1)

• Buchalter ELF, Oughli HA, Lenze EJ, Dixon D, Miller JP, Blumberger DM, Karp JF, Reynolds CF 3rd, Mulsant BH. Predicting Remission in Late-Life Major Depression: A Clinical Algorithm Based Upon Past Treatment History. J Clin Psychiatry. 2019 Dec 10;80(6):18m12483. doi: 10.4088/JCP.18m12483.

  PMID: 31846575 DERIVED

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

Study Officials

• Daniel M Blumberger, MD

  CAMH

  PRINCIPAL INVESTIGATOR

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: Dr. Daniel. M. Blumberger

Study Record Dates

• First Submitted: October 8, 2014
• First Posted: October 13, 2014
• Study Start: December 1, 2014
• Primary Completion: January 19, 2017
• Study Completion: May 1, 2018
• Last Updated: July 26, 2018

Record last verified: 2018-07

Locations

CA (1)