Functional Brain Mechanisms Underlying the Anti-Suicidal Effects of Low-dose Buprenorphine in Major Depression

  • STATUS
    Recruiting
  • End date
    Jun 30, 2023
  • participants needed
    30
  • sponsor
    New York State Psychiatric Institute
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Updated on 23 October 2022
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depression
depressed mood

Summary

This study aims to examine the effect of low-dose buprenorphine as an add-on to treatment-as-usual for suicidal ideation in individuals with major depression, and investigate the functional brain activity related to its potential anti-suicidal effect.

Description

Buprenorphine is an approved treatment for pain and opioid relapse prevention. Buprenorphine has recently shown promise in the treatment of depression and suicidal ideation relatively faster than currently available antidepressants, but its mechanisms in treating these conditions are unknown. Buprenorphine activates the mu opioid receptor in the brain and blocks the kappa opioid receptor. Activation of the mu receptors produces pleasant emotions while the kappa receptors are linked to dysphoria and other negative emotional states. By blocking kappa receptors, buprenorphine may reduce negative emotions and improve suicidal thoughts.

In this project, we will compare buprenorphine to placebo as adjunctive to usual treatments for patients who still have depression and suicidal thoughts despite being treated with adequate antidepressant medications for at least 4 weeks. We hypothesize that suicidal ideation will decrease after two weeks of treatment in the buprenorphine group relative to the placebo group.

Using functional magnetic resonance imaging, we will also examine the effects of buprenorphine on the activity of brain regions involved in the brain's response to negative emotions and test whether these effects are associated with the reduction in suicidal thoughts. This would provide some evidence that the antidepressant and anti-suicidal effects of buprenorphine are related to its kappa opioid receptor blockade.

The mechanism of action of buprenorphine is different from the currently available antidepressants. This study will help understand this mechanism which may help refine the use of buprenorphine in this context. Research in this area may also facilitate the development of new anti-suicidal treatments (i.e., other opioid-active compounds).

Details
Condition Suicidal Ideation, Major Depressive Disorder
Treatment Placebo, Belbuca Buccal Product
Clinical Study IdentifierNCT05427981
SponsorNew York State Psychiatric Institute
Last Modified on23 October 2022

Eligibility

 Yes No Not Sure

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the
following criteria
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the
duration of the study
Male or female
Aged 18-65 years
Ability to take oral medication and be willing to adhere to the treatment regimen
Current major depressive episode
Hamilton Depression Rating Scale (HDRS) Score > 16
Active suicidal ideation (Columbia Suicide Severity Rating Scale (C-SSRS) of 3 or
more)
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
Current active psychosis or mania
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
Family history of alcohol or substance use disorder in a first-degree relative
Current or past history of prescription or non-prescription opioid use
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)
Current acute or chronic pain
Neurological disorders (e.g., epilepsy, brain tumors or patients with increased
intracranial pressure due to other reasons)
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
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)
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))
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
Known allergy or sensitivity to buprenorphine
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
Inability to read and speak English fluently
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
Claustrophobia significant enough to interfere with MRI scanning
Weight over 350 lbs or inability to fit into MRI scanner
Clear my responses
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