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 the following criteria: 1. Provision of signed and dated informed consent form. 2. Stated willingness to comply with all study procedures and availability for the duration 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 or more). 9. Participants must have been on a medication regimen for depression that includes an adequate 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 participation in this study: 1. Current active psychosis or mania. 2. Current or past alcohol use disorder or substance use disorder involving any prescribed or any illicit drug (opioid, benzodiazepine, or other drug use) including mild 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 use disorder 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 increased intracranial pressure due to other reasons). 8. A history of prior head trauma with evidence of cognitive impairment. Participants who endorse a history of prior head trauma will be administered the Trail-making A and B test. Those who score 1.5 standard deviations below the mean on the Trail-making A or B will be excluded from study participation. 9. Active significant medical illness that would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study (e.g., oral mucositis, orthostatic hypotension, history of hypotensive disorders, hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia, history of Long QT syndrome or immediate family member with this condition, moderate to severe hepatic impairment or hepatitis, liver cirrhosis , severe chronic pulmonary diseases, significant respiratory depression, acute or severe bronchial asthma, known or suspected gastrointestinal obstruction, including paralytic ileus). 10. Participants taking medications that prolong the QT interval (e.g., Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide)). 11. Participants taking medications with potentially clinically-significant drug interactions 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 reverse transcriptase inhibitors (e.g., efavirenz, nevirapine, etravirine, delavirdine), protease inhibitors (e.g., atazanavir, ritonavir). Additionally, patients must discontinue 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, current breastfeeding or plans to conceive during the course of study participation. Patients who are not on contraceptives will be asked to at least use barrier methods during sexual intercourse. All patients must commit to not attempting to become pregnant during participation in the study. 14. Inability to read and speak English fluently. 15. Metal implants or paramagnetic objects contained within the body (including heart pacemaker, shrapnel, or surgical prostheses) which may present a risk to the subject or interfere with the MR scan, according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic 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.