Effects of Buprenorphine on Mood in Adults With a Range of Depressive Symptomatology

NCT ID: NCT02659787

Last Updated: 2019-05-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-30
• Study Completion Date: 2017-04-30

Brief Summary

This study seeks to to study the effects of buprenorphine, a partial mu-opioid agonist, on depressed mood in a healthy young adults with a range of depressive symptomatology.

Detailed Description

It has been shown that opioid analgesics, particularly the mu-opioid partial agonist buprenorphine, have anti-depressant properties in laboratory animal models. In humans, rates of prescription opioid abuse are significantly higher in patients with depression. This suggests that individuals with negative mood states (e.g., depressive states) may respond more positively to opioid drugs. A handful of small studies in in humans have suggested that buprenorphine reduces symptoms of depression in patients who did not respond to standard anti-depressants, and laboratory studies have shown buprenorphine may reduce responses to some types of negative stimuli and enhance responses to positive stimuli. However, a controlled laboratory study assessing potential anti-depressant effects of an opioid medication has never been conducted. In this project, the investigators propose to examine depressive symptomatology as a predictor of subjective mood responses to buprenorphine, using two measures; i) self-reported depressive symptomatology as measured by the Beck Depression Inventory (BDI-II), and ii) physiological indices of depressive symptomatology as measured by heart rate variability. Reduced heart rate variability has been shown to be associated with depression, and such a physiological measure may allow for the detection of more subtle effects than would a self-report questionnaire alone. Healthy volunteers (N=60) will first complete the BDI and provide baseline measures of heart rate variability. Then they will attend two laboratory sessions, at which they will receive placebo or 0.2mg buprenorphine. The investigators have tested these low doses of buprenorphine in previous studies, and they produce measurable changes in mood and behavior in healthy volunteers. The investigators will collect measures of mood and physiological drug response (pupillometry, heart rate, and blood pressure) at regular intervals throughout each session, and will then examine their baseline indices of depressive symptomatology in relation to responses to the drug. The central hypothesis is that individuals with greater self-reported depressive symptoms and lower heart rate variability will experience the greatest enhancement of mood in response to buprenorphine. It is expected that this work will provide a better understanding of which individuals are most likely to experience positive mood effects in response to opioid drugs, and may therefore be at-risk for developing an opioid use disorder. Furthermore, it may lay the foundation for future research in the development of novel opioid-based treatments for depression.

Design: The study will use a 3-session within-subjects double-blind design in which participants will receive single doses of buprenorphine (0, 0.2 mg sublingual) in randomized order. All screening, orientation, and study session procedures will take place in the Human Behavioral Pharmacology Laboratory suite in the L4 wing of 5841 S. Maryland Ave.

Drug and Doses: Investigators will administer placebo, 0.2 mg buprenorphine (Temgesic) via sublingual tablet in counterbalanced order under double-blind conditions. These tablets dissolve within 5-8 minutes. This drug has been approved for treatment of severe pain. The onset of action after sublingual administration is 30 minutes, with a peak plasma concentration at 1/5-2 hours and a half-life of 5 hours. The dose of buprenorphine are very low, and the average maintenance dose for opioid abusers is 8 mg. Doses will be separated by at least 72 hours.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Low dose buprenorphine

Subjects all receive placebo, 0.2 mg buprenorphine in crossover design

Group Type: ACTIVE_COMPARATOR

0.2mg Buprenorphine

Intervention Type: DRUG

Sublingual buprenorphine tablets (0.2mg)

Placebo

Subjects all receive placebo, 0.2 mg buprenorphine in crossover design

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

0.2mg Buprenorphine

Sublingual buprenorphine tablets (0.2mg)

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Healthy adult volunteers
• High school education
• Fluency in English
• BMI between 19 and 30

Exclusion Criteria

• Medical conditions contraindicating study participation
• Regularly medication use
• Current or past opioid abuse or dependence
• Current or past drug or alcohol dependence
• Psychiatric illness
• Women who are pregnant or nursing

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Chicago

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Chicago

Chicago, Illinois, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 25178815 (View on PubMed)

Sullivan MD, Edlund MJ, Steffick D, Unutzer J. Regular use of prescribed opioids: association with common psychiatric disorders. Pain. 2005 Dec 15;119(1-3):95-103. doi: 10.1016/j.pain.2005.09.020. Epub 2005 Nov 17.

Reference Type: BACKGROUND

PMID: 16298066 (View on PubMed)

Karp JF, Butters MA, Begley AE, Miller MD, Lenze EJ, Blumberger DM, Mulsant BH, Reynolds CF 3rd. Safety, tolerability, and clinical effect of low-dose buprenorphine for treatment-resistant depression in midlife and older adults. J Clin Psychiatry. 2014 Aug;75(8):e785-93. doi: 10.4088/JCP.13m08725.

Reference Type: BACKGROUND

PMID: 25191915 (View on PubMed)

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Reference Type: BACKGROUND

PMID: 18794671 (View on PubMed)

Bodkin JA, Zornberg GL, Lukas SE, Cole JO. Buprenorphine treatment of refractory depression. J Clin Psychopharmacol. 1995 Feb;15(1):49-57. doi: 10.1097/00004714-199502000-00008.

Reference Type: BACKGROUND

PMID: 7714228 (View on PubMed)

Striebel JM, Kalapatapu RK. The anti-suicidal potential of buprenorphine: a case report. Int J Psychiatry Med. 2014;47(2):169-74. doi: 10.2190/PM.47.2.g.

Reference Type: BACKGROUND

PMID: 25084802 (View on PubMed)

Licht CM, de Geus EJ, Zitman FG, Hoogendijk WJ, van Dyck R, Penninx BW. Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). Arch Gen Psychiatry. 2008 Dec;65(12):1358-67. doi: 10.1001/archpsyc.65.12.1358.

Reference Type: BACKGROUND

PMID: 19047522 (View on PubMed)

Ipser JC, Terburg D, Syal S, Phillips N, Solms M, Panksepp J, Malcolm-Smith S, Thomas K, Stein DJ, van Honk J. Reduced fear-recognition sensitivity following acute buprenorphine administration in healthy volunteers. Psychoneuroendocrinology. 2013 Jan;38(1):166-70. doi: 10.1016/j.psyneuen.2012.05.002. Epub 2012 May 30.

Reference Type: BACKGROUND

PMID: 22651957 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

14-0170

Identifier Type: -

Identifier Source: org_study_id