Add-on Buprenorphine at Analgesic Doses for the Treatment of Severe Suicidal Ideas During a Major Depressive Episode (BUPRIS)

This study aims at investigating if adjunctive buprenorphine at low dose to treatment as usual is effective in reducing severe suicidal ideas in major depressive episode, and at determining the most effective dose.

Study Overview

• Status: Recruiting
• Conditions: Suicidal Ideation; Major Depressive Episode
• Intervention / Treatment: Drug: Placebo; Drug: Buprenorphine

Detailed Description

Participants will be randomized to two doses of buprenorphine (0.4mg and 0.8mg) or placebo. The duration of treatment will be 21 days with 7 days withdrawal period. Two follow-up phone calls at 3 and 6 months will investigate occurence of suicidal behavior.

The main outcome will be changes in suicidal ideas levels during the first week.

Secondary outcomes will be changes in suicidal ideas during the following 21 days, changes in depression and psychological pain levels over the first 28 days, dropout rates, reasons and occurence of side effects over the first 28 days, withdrawal symptoms dung the withdrawal period, changes in neuropsychological and neuroimaging measures between Day 0 and Day 28.

Blood and stool samples will be collected at 4 time points and stored in a biobank for future analyses.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fabrice Jollant, MD; Phone Number: +33(0)1 45 65 85 72; Email: fabrice.jollant@parisdescartes.fr

Study Locations

• France
  • Bordeaux, France, 33076
    • Not yet recruiting
    • Ch Perrens
    • Contact: TOURNIER MARIE, PUPH; Phone Number: 05 56 56 17 71; Email: mtournier@ch-perrens.fr
  • Le Kremlin-Bicêtre, France, 94270
    • Recruiting
    • CHU Bicêtre
    • Contact: Emmanuelle Corruble, MD; Phone Number: +33(0)1 45 21 25 24; Email: emmanuelle.corruble@bct.aphp.fr
  • Lyon, France, 69003
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Emmanuel Poulet, MD; Phone Number: +33(0)4 72 11 00 09; Email: emmanuel.poulet@chu-lyon.fr
  • Nantes, France, 44000
    • Recruiting
    • CAPPA Jacques PREVERT
    • Contact: Anne Sauvaget, MD; Phone Number: +33(0)2.40.08.47.95; Email: anne.sauvaget@chu-nantes.fr
  • Nîmes, France, 30029
    • Recruiting
    • CHU Nimes
    • Sub-Investigator: Fabricio PEREIRA
    • Contact: Mocrane Abbar, MD; Phone Number: +33 (0)4.66.68.42.36; Email: m-abbar@chu-nimes.fr
    • Sub-Investigator: Jorge Lopez Castroman, MD
    • Sub-Investigator: Ismaël Conegero, MD
  • Paris, France, 75674
    • Recruiting
    • CH Sainte-Anne
    • Contact: Fabrice Jollant, MD; Phone Number: +33 (0)1 45 55 65 92; Email: fabrice.jollant@parisdescartes.fr
  • Poitiers, France, 86021
    • Recruiting
    • CH Henri Laborit
    • Contact: Nemat Jaafari, MD; Phone Number: +33(0)5 16 52 61 18; Email: nemat.jaafari@ch-poitiers.fr
  • Toulouse, France, 31059
    • Not yet recruiting
    • CHU Toulouse Hôpital Purpan
    • Contact: YRONDI ANTOINE, M.D.,Ph.D.; Email: yrondi.a@chu-toulouse.fr
  • Tours, France, 37540
    • Recruiting
    • Chu De Tours
    • Contact: Wissam El-Hage, MD; Phone Number: +33(0)2 47 47 80 43; Email: wissam.elhage@univ-tours.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The patient has been correctly informed.
• The patient must have given his/her informed and signed the consent form.
• The patient must be insured or beneficiary of a health insurance plan.
• The patient is at least 18 years old and 65 years old at the most.
• The patient is hospitalized or followed in consultation.
• The patient has a current major depressive episode without psychotic features according to the criteria of the "Diagnostic and Statistical Manual of Mental Disorders"
• The patient has a score > 20 of the "Montgomery-Asberg Depression Rating Scale".
• The patient has a current Scale for Suicidal Ideation (SSI) score > 8.

Exclusion Criteria:

• The patient is participating in another interventional trial;
• The patient is in an exclusion period determined by a previous study;
• The patient is under judicial protection, or is an adult under guardianship;
• The patient is under compulsory admission;
• The patient refuses to sign the consent;
• it is impossible to correctly inform the patient.
• The patient is pregnant or breastfeeding.
• The patient suffers from schizophrenia;
• The patient suffered from moderate to severe alcohol use disorder or substance use disorder (except tobacco and caffeine) over the last 12 months according to DSM-5 criteria ;
• The patient currently suffers from severe and/or unstable medical condition (including severe respiratory or hepatic insufficiency) or a painful medical condition;
• The patient has a current known sleep apnea.
• The patient currently takes analgesic treatment (including Nonsteroidal anti-inflammatory drug and paracetamol);
• The patient currently takes central nervous depressant drugs at sedative doses (based on the investigator's assessment), including benzodiazepines, antihistamines, and sedative antipsychotics;
• The patient currently takes major CYP3A4 Inhibitors and inducers;
• The patient currently takes has received Electroconvulsivotherapy over the last 3 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; 2 placebo pills sublingual during 28 days	Drug: Placebo; Placebo pills, sublingual, specifically made to mimick buprenorphine pills
Experimental: 0.4mg buprenorphine; 1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 21 days, then 2 placebo pills per day for 1 week, all sublingual.	Drug: Buprenorphine; Buprenorphine, 0.4mg pills, sublingual; Other Names: Temgesic
Experimental: 0.8mg buprenorphine; 1 pill of 0.4 mg buprenorphine + 1 placebo pill per day for 3 days, then 2 pills of 0.4mg buprenorphine per day for 18 days, then 1 pill of 0.4 mg + 1 placebo pill per day for 3 days, then 2 placebo pills per day for 4 days, all sublingual.	Drug: Buprenorphine; Buprenorphine, 0.4mg pills, sublingual; Other Names: Temgesic

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Beck Scale for Suicidal Ideation (SSI) scores from Day 0 to 7	Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted), higher scores mean more intense suicidal ideas.	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Beck Scale for Suicidal Ideation (SSI) scores	Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted); higher scores mean more intense suicidal ideas.	Day 8 to day 28
Changes in Beck Depression Inventory II (BDI-II) scores from Day 0 to 28	Self questionnaire measuring depression level over the last 7 days; 13 items scored 0 to 3, with the total score ranging from 0 to 39; higher scores mean higher level of depression.	28 days
Changes in Montgomery-Asberg Depression Rating Scale (MADRS) from Day 0 to 28	Clinician-based questionnaire measuring the level of depression of the last 7 days; 10 items score 0 to 6, with the total scores ranging fron 0 to 60; Higher scores mean higher level of depression.	28 days
Changes in Physical and Psychological Pain - Visual Analog Scale (PPP-VAS) scores from Day 0 to 28	Visual Analog Scale measuring physical then psychological pain over 3 periods each (current, worst over the last 7 days, mean over the last 7 days); 6 dimensions in total; each dimension is scored from 0 (no pain) to 10 (maximal pain).	28 days
Reasons for discontinuing treatment over the first 28 days	Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.	28 days
Side effects over the first 28 days	Patient's self-report; measurement will be the overall (over 28 days) incidence for each event reported.	28 days
Withdrawal symptoms	Patient's self-report; measurement will be the incidence of any withdrawal symptom during the withdrawal phase.	Day 22 to day 28
Occurence of a suicide attempt during the whole study	Interview based; measurement will be the incidence of any suicide attempt between Day 0 and 28, between Day 29 and 90, and between Day 90 and 180.	180 days
Changes in Iowa Gambling Task (IGT) scores between Day 0 and 28	Computerized test measuring decision-making; scores are the difference between advantageous and disadvantageous choices; scores range from -100 to + 100, higher scores means better performance	28 days
Changes in modified Stroop test scores between Day 0 and 28	Classical Stroop test modified with suicide-related words to measure specific attention bias; scores are the number of errors and total reaction time; higher scores mean worse performance	28 days
Changes in verbal fluency test scores between Day 0 and 28	Classical test measuring verbal fluency skills for semantic and phonological categories; Patients are instructed to give as many words as possible for a given category then for words starting with a given letter, within a 1 minute time frame; Scores are the number of correct words; higher scores mean higher performance	28 days
Changes in N-Back test scores between Day 0 and 28	Classical test of working memory using letters; scores are the number of words correctly identified for each level of recall (0 to 2 back); higher scores mean better performance; also, the number of omission and commission errors.	28 days
Changes in Go/No-Go test between Day 0 and 28	Classical test of cognitive inhibition, letter version; scores are the number of omission and commission errors (higher scores mean worse performance) and reaction times (higher scores mean better performance)	28 days
Changes in Trail Making Test (TMT) scores between Day 0 and 28	Classical test of planning abilities; scores are the difference between the time to complete parts B and A of the test; Higher scores mean worse performance.	28 days
Changes in Implicit Association Test (IAT) scores between Day 0 and 28	IAT version adapted for suicide/death; scores are the measure of reaction times in the association between suicide/death words and me/myself words; lower scores mean higher association.	28 days
Changes in Magnetic Resonance Imaging (MRI) T1 measures between Day 0 and 28	Brain structural MRI-T1 sequence measured at Day 0 and Day 28 (5 minutes)	28 days
Changes in Magnetic Resonance Imaging (MRI) T2 measures between Day 0 and 28	Brain structural MRI-T2 sequence measured at Day 0 and Day 28 (5 minutes)	28 days
Changes in Magnetic Resonance Imaging (MRI) Diffusion Tensor Imaging (DTI) measures between Day 0 and 28	Brain Diffusion Tensor Imaging (DTI) sequence measured at Day 0 and Day 28 (20 minutes)	28 days
Changes in Magnetic Resonance Imaging (MRI) Resting State (RS) measures between Day 0 and 28	Brain functional Resting State (RS) sequence measured at Day 0 and Day 28 (15 minutes)	28 days

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Fabrice Jollant, MD, Hôpital Sainte-Anne

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: August 16, 2018
• First Submitted That Met QC Criteria: August 22, 2018
• First Posted (Actual): August 24, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 19, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Depression; Treatment; Buprenorphine; Mental pain; Suicidal ideas; Opioid agonist
• Additional Relevant MeSH Terms: Mental Disorders; Behavioral Symptoms; Self-Injurious Behavior; Mood Disorders; Suicide; Suicidal Ideation; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Peripheral Nervous System Agents; Central Nervous System Depressants; Sensory System Agents; Analgesics; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine
• Other Study ID Numbers: PHRC-N/2017/FJ-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No