Nalrexone Facilitated Discontinuation of Buprenorphine
| Status: | Completed |
|---|---|
| Conditions: | Gastrointestinal |
| Therapuetic Areas: | Gastroenterology |
| Healthy: | No |
| Age Range: | 18 - 49 |
| Updated: | 6/17/2018 |
| Start Date: | February 2011 |
| End Date: | September 2013 |
The efficacy of buprenorphine as a long-term agonist treatment has been offset by the
emergence of intolerable withdrawal phenomena in a subset of individuals on chronic
maintenance who attempt to discontinue the medication. Efforts are needed to better
understand these challenges encountered with buprenorphine, as well as to develop
interventions to facilitate medication discontinuation.
Emerging evidence suggests that these difficulties may be related to the unique effects of
buprenorphine on sites other than mu-opioid receptors, such as kappa-opioid receptors.
Kappa-opioid agonism produces aversive, dysphoric-like effects, and can also increase the
likelihood of reinstatement to drug use through stress-mediated mechanisms. Some of the
discomfort observed during drug taper may therefore be due to the attenuation or loss of
kappa-opioid antagonism afforded by buprenorphine, as well as to rebound kappa-opioid
activation. Naltrexone represents a promising candidate for extending kappa blockade and
therefore for facilitating discontinuation attempts. Naltrexone and its active metabolite
6-Beta-naltrexol are competitive antagonists at the mu and kappa receptors, and to a lesser
extent at the delta receptor. Naltrexone and buprenorphine have comparable affinity for the
mu-opioid receptor and thus buprenorphine is displaced by naltrexone more gradually than are
other opioids with less affinity; a careful titration of naltrexone is less likely,
therefore, to precipitate severe withdrawal states in individuals coming off buprenorphine,
and the two have been combined to good effect in other settings.
The purpose of this study is therefore to investigate the feasibility of naltrexone
augmentation on discontinuing buprenorphine in eligible patients on long-term maintenance.
emergence of intolerable withdrawal phenomena in a subset of individuals on chronic
maintenance who attempt to discontinue the medication. Efforts are needed to better
understand these challenges encountered with buprenorphine, as well as to develop
interventions to facilitate medication discontinuation.
Emerging evidence suggests that these difficulties may be related to the unique effects of
buprenorphine on sites other than mu-opioid receptors, such as kappa-opioid receptors.
Kappa-opioid agonism produces aversive, dysphoric-like effects, and can also increase the
likelihood of reinstatement to drug use through stress-mediated mechanisms. Some of the
discomfort observed during drug taper may therefore be due to the attenuation or loss of
kappa-opioid antagonism afforded by buprenorphine, as well as to rebound kappa-opioid
activation. Naltrexone represents a promising candidate for extending kappa blockade and
therefore for facilitating discontinuation attempts. Naltrexone and its active metabolite
6-Beta-naltrexol are competitive antagonists at the mu and kappa receptors, and to a lesser
extent at the delta receptor. Naltrexone and buprenorphine have comparable affinity for the
mu-opioid receptor and thus buprenorphine is displaced by naltrexone more gradually than are
other opioids with less affinity; a careful titration of naltrexone is less likely,
therefore, to precipitate severe withdrawal states in individuals coming off buprenorphine,
and the two have been combined to good effect in other settings.
The purpose of this study is therefore to investigate the feasibility of naltrexone
augmentation on discontinuing buprenorphine in eligible patients on long-term maintenance.
Inclusion Criteria:
1. Adult, aged 18-49.
2. Currently maintained on buprenorphine, with a clinically acceptable interest in
tapering or discontinuing it
3. Willingness to switch over to naltrexone
4. In otherwise good health based on complete medical history, physical examination,
vital signs measurement, ECG, and laboratory tests (hematology, blood chemistry,
urinalysis) within normal ranges.
5. Able to give informed consent and comply with study procedures,
6. Currently on 2 mg or less of buprenorphine.
7. Voluntarily seeking treatment for opioid dependence.
Exclusion Criteria:
1. Significant current suicidal risk or 1 or more suicide attempts within the past year
2. History of accidental drug overdose in the last three years defined as an episode of
opioid-induced unconsciousness or incapacitation, whether or not medical treatment was
sought or received.
3. Positive serum pregnancy test, lactation, or unwillingness to use a satisfactory
method of birth control
4. Active psychiatric disorder which might interfere with participation or make
participation hazardous, including DSM-IV organic mental disorder, psychotic disorder,
or bipolar disorder with mania
5. History of allergic reaction, adverse reaction, or sensitivity to any study
medication.
6. Acute hepatitis with SGOT or SGPT > 3 times the upper end of the laboratory normal
range (chronic hepatitis is acceptable as we have found naltrexone treatment well
tolerate and safe among patients with chronic hepatitis)
7. Currently prescribed or regularly taking opioids for chronic pain
8. Current participation in another intensive psychotherapy or substance abuse treatment
program, or participation in another treatment study.
9. Opioid dependence is not well-managed, and characterized by relapses, slips, or missed
doses
10. Concurrent treatment with psychotropic medications which may interact adversely with
naltrexone, such as duloxetine and valproic acid.
We found this trial at
1
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