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.

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.

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.