Anti-suicidal Effects of Buprenorphine In Depressed Individuals

Inclusion Criteria: In order to be eligible to participate in this study, an individual must meet all of thefollowing criteria:

1. Provision of signed and dated informed consent form.
2. Stated willingness to comply with all study procedures and availability for theduration of the study.
3. Male or female.
4. Aged 18-65 years.
5. Ability to take oral medication and be willing to adhere to the treatment regimen.
6. Current major depressive episode.
7. Hamilton Depression Rating Scale (HDRS) Score > 16.
8. Active suicidal ideation (Columbia Suicide Severity Rating Scale (C-SSRS) of 3 ormore).
9. Participants must have been on a medication regimen for depression that includes anadequate dose of antidepressant for at least the past 4 weeks.

Exclusion Criteria: An individual who meets any of the following criteria will be excluded from participationin this study:

1. Current active psychosis or mania.
2. Current or past alcohol use disorder or substance use disorder involving anyprescribed or any illicit drug (opioid, benzodiazepine, or other drug use) includingmild severity.
3. Family history of alcohol or substance use disorder in a first-degree relative.
4. Current or past history of prescription or non-prescription opioid use.
5. History of other risk factors for the development of opioid misuse and opioid usedisorder other than comorbid depression (e.g., homelessness, criminal record,aggressive or violent behavior that resulted in injury to another person).
6. Current acute or chronic pain.
7. Neurological disorders (e.g., epilepsy, brain tumors or patients with increasedintracranial pressure due to other reasons).
8. A history of prior head trauma with evidence of cognitive impairment. Participants whoendorse a history of prior head trauma will be administered the Trail-making A and Btest. Those who score 1.5 standard deviations below the mean on the Trail-making A orB will be excluded from study participation.
9. Active significant medical illness that would make study participation hazardous tothe participant or compromise study findings or would prevent the participant fromcompleting the study (e.g., oral mucositis, orthostatic hypotension, history ofhypotensive disorders, hypokalemia, hypomagnesemia, or clinically unstable cardiacdisease, including unstable atrial fibrillation, symptomatic bradycardia, unstablecongestive heart failure, or active myocardial ischemia, history of Long QT syndromeor immediate family member with this condition, moderate to severe hepatic impairmentor hepatitis, liver cirrhosis , severe chronic pulmonary diseases, significantrespiratory depression, acute or severe bronchial asthma, known or suspectedgastrointestinal obstruction, including paralytic ileus).
10. Participants taking medications that prolong the QT interval (e.g., Class IAantiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class IIIantiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide)).
11. Participants taking medications with potentially clinically-significant druginteractions with BELBUCA , including benzodiazepines, central nervous system (CNS)depressants (e.g., alcohol, anxiolytics, general anaesthetics, hypnotics,neuroleptics, phenothiazines, sedatives, tranquilizers), other opioid analgesics,muscle relaxants, diuretics, anticholinergic drugs, non-nucleoside reversetranscriptase inhibitors (e.g., efavirenz, nevirapine, etravirine, delavirdine),protease inhibitors (e.g., atazanavir, ritonavir). Additionally, patients mustdiscontinue CYP3A4 strong inhibitors (e.g., clarithromycin, telithromycin, nefazodone,itraconazole, ketoconazole) 2 weeks before initiation of the study.
12. Known allergy or sensitivity to buprenorphine.
13. If female, pregnancy, abortion or miscarriage in the previous two months, currentbreastfeeding or plans to conceive during the course of study participation. Patientswho are not on contraceptives will be asked to at least use barrier methods duringsexual intercourse. All patients must commit to not attempting to become pregnantduring participation in the study.
14. Inability to read and speak English fluently.
15. Metal implants or paramagnetic objects contained within the body (including heartpacemaker, shrapnel, or surgical prostheses) which may present a risk to the subjector interfere with the MR scan, according to the guidelines set forth in the followingreference book commonly used by neuroradiologists: "Guide to MR procedures andmetallic objects", F. G. Shellock, Lippincott Williams and Wilkins NY 2001.Additionally, transdermal patches will be removed during the MRI.
16. Claustrophobia significant enough to interfere with MRI scanning.
17. Weight over 350 lbs or inability to fit into MRI scanner.