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Program Profile: Buprenorphine Maintenance Treatment

Evidence Rating: Effective - More than one study Effective - More than one study

Date: This profile was posted on June 10, 2011

Program Summary

Used in the treatment of patients with opioid dependence to alleviate withdrawal symptoms, suppress opiate effects and cravings, and decrease the risk of overdose. The program is rated Effective. The experimental group had more days of participation, treatment retention, decreased drug use, improved well-being and mental health. Participants had significantly reduced opiate cravings.

Program Description

Program Goals

Buprenorphine maintenance treatment (BMT) is used to treat individuals with opioid dependence. As with methadone maintenance treatment, the goals of BMT are to alleviate withdrawal symptoms, suppress opiate effects and cravings, and decrease the risk of overdose as a result of the illicit use of opioids.

 

Program Components

Opioids such as heroin or morphine cause a release of excess dopamine in the body. Users become dependent on the drug because they need opiates to continuously occupy the opioid receptor in the brain. Similar to methadone, buprenorphine works by occupying this receptor and blocking the high that usually comes from illicit opioid drug use.

 

Buprenorphine exerts a weaker agonist effect at opioid receptor sites because it is a partial agonist. The effects of buprenorphine increase as the dosage of the drug are increased, until at moderate doses the effects reach a plateau and no longer continue to grow (known as the ceiling effect). The maximal effects of buprenorphine are usually reached in the 16–32 milligram (mg) dose range. Methadone causes a stronger agonist effect because it is a full agonist. However, there is no ceiling to the level of effects that methadone can induce, which can lead to fatal overdoses if the drug is used illicitly. Thus, buprenorphine can be used as a viable pharmacological alternative to methadone because it carries a lower risk of abuse, overdose, and side effects than do full opioid agonists.

 

Another benefit is the dosing schedule. Although the effects of buprenorphine are not as strong as methadone, they last longer. While methadone requires daily dosing, buprenorphine can be taken once every 2 days. This can be an advantage in BMT because opioid-addicted patients may be turned off to treatment that requires daily dosage and visits to the clinics, whereas buprenorphine offers the option of alternate day dosing.

 

In addition, buprenorphine can be dispensed in office-based settings. Although methadone can only be dispensed from federally licensed opioid treatment programs, buprenorphine can be administered by physicians in their offices.

 

There are generally three stages of BMT: induction, stabilization, and maintenance. During the induction phase, patients are medically monitored during the beginning of the buprenorphine therapy. The stabilization phase begins once patients have greatly reduced or stopped their opioid abuse. At this phase they no longer have cravings and experience few or no side effects. The dosage may be adjusted during this phase. Finally, the maintenance phase is reached once patients are on a steady dose of buprenorphine. The length of time patients continue to receive BMT varies by individual and may be indefinite.

 

On top of administering medication, BMT can provide patients with comprehensive rehabilitation services. Services can include group therapy, individual therapy, medical services, and referrals to community-based agencies.

 

Additional Information

Buprenorphine can also be prescribed in combination with naloxone, a drug that is used to counter the effect of opiate overdose. Naloxone is added to buprenorphine to reduce the likelihood of diversion and abuse of the medication.

Evaluation Outcomes

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Study 1

Days of Participation

The results from the randomized trial conducted by Krook and colleagues (2002) found that the buprenorphine group had significantly more days of participation compared with the placebo group. The buprenorphine group had an average of 42 days of participation, while the placebo group had an average of 14 days of participation. Log-rank tests of equality of survival distributions also showed the two groups were significantly different.

 

Treatment Retention

After 12 weeks of treatment, only 16 patients in the buprenorphine group and 1 patient in the placebo group completed the program. The most common reason for dropping out before the 12 weeks was patients missing 4 consecutive days of treatment (which meant that further medication was withdrawn and they were considered noncompleters).

 

Drug Use

The self-reported use of heroin or other drugs decreased significantly in the buprenorphine group compared with the placebo group. The 16 patients who completed the 12 weeks of buprenorphine treatment had a larger decrease in reported heroin use and use of other drugs compared with the patients in the buprenorphine group who did not complete treatment.

 

Well-being and Mental Health

The buprenorphine group showed a significantly larger increase in self-reported well-being compared with the placebo group. There were no significant differences between the two groups in reporting of anxiety and depression. The buprenorphine treatment completers reported a larger increase in well-being and life satisfaction and a larger decrease in anxiety and depression compared with treatment noncompleters.

 

Some self-reported positive effects of treatment were reported significantly more often in the buprenorphine group, including fewer cravings, having a more normal life, and feeling more content to live.

 

Study 2

Opiate and Other Drug Use

Fudala and colleagues (2003) found that during the double-blind trial both of the buprenorphine-based treatments significantly reduced opiate use. The percentage of urine tests that were opiate negative was 17.8 percent in the buprenorphine and naloxone combination treatment group and 20.7 percent in the buprenorphine-only group, compared with 5.8 percent in the placebo group.

 

The drug (other than opiates) most commonly detected in the urine tests was cocaine. The frequency of cocaine-positive samples did not differ significantly between the three groups. There was also no difference in the frequency of samples that tested positive for benzodiazepines, amphetamines, barbiturates, and methadone, but those drugs were detected in fewer than 5 percent of the samples.

 

During the open-label study in which all participants received the combination of buprenorphine with naloxone, the percentage of opiate-negative urine samples ranged from 35.2 percent to 67.4 percent throughout the 48-week study. The overall rate of opiate use was lower than the double-blind trial, whereas the use of cocaine and benzodiazepines remained relatively constant.

 

Opiate Cravings

The buprenorphine-based treatments also significantly reduced cravings for opiates. The mean craving scores in the combination treatment group and buprenorphine-only group were significantly lower than in the placebo group.

 

Health and Well-being

In addition, the overall self-reported health and well-being of participants in the combined-treatment and buprenorphine-only groups improved to a significantly greater extent than it did in the placebo group. In all groups, participants’ self-reports of their overall status relative to the previous assessments showed improvements, but the improvements were not statistically significant.

 

Adverse Events

The overall rate of adverse effects did not differ significantly among the three groups in the double-blind trial. Seventy-eight percent of the combination treatment group, 85 percent of the buprenorphine-only group, and 80 percent of the placebo group reported adverse effects such as headache, withdrawal syndrome, pain, or insomnia. Only 20 percent of the participants reported adverse events in the open-label study.

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Evaluation Methodology

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Study 1

Krook and colleagues (2002) employed a 12-week, randomized, double-blind study of buprenorphine versus placebo without additional rehabilitation or support services. The study was conducted through the Centre for Medication Assisted Rehabilitation in Oslo, Norway (MARIO). Study participants were 420 patients on the waiting list for MARIO. They received a letter offering a chance to participate in the study if they met the inclusion criteria: they had to be at least 25 years old, have a history of more than 10 years of opioid dependence, and have a written plan for the rehabilitation process. In addition, participants had to have a current opioid dependence and to have already attempted drug-free treatment.

 

The final sample included 106 patients who were randomly assigned to a placebo group (n= 51) or a buprenorphine treatment group (n= 55). The placebo group was 67.0 percent male, with an average age of 38 years and an average drug use history of 20-year heroin addiction. The buprenorphine treatment group was 65.5 percent male, with an average age of 38 years and an average drug use history of 20-year heroin addiction. There were no significant differences between the groups in any of the demographic or baseline characteristics.

 

The primary outcome variables were retention and compliance. Participants were also asked to self-report drug use using a visual analog scale (VAS) from 0 to 10, where “daily heavy drug use” was recorded as 10 and “drug free” was recorded as 0. Abuse of opioids was calculated separately, while benzodiazepines, other drugs, and alcohol were calculated together. Subjective well-being was also self-reported using a VAS (where 10 meant “very bad” and 0 meant “very well”) and with the temporal satisfaction with life scale. Mental health, including anxiety and depression, was measured with the symptom checklist.

 

Survival analysis was used to examine study participation and attrition of patients. T–tests were used to analyze the treatment effect on the other outcome variables by comparing the change in the scores of the placebo group with the change in the scores of the buprenorphine group.

 

Study 2

Fudala and colleagues (2003) examined the efficacy of buprenorphine in combination with naloxone in an office-based setting. There were two parts of the study that took place across multiple treatment centers. The first part was a 4-week, double-blind, placebo-controlled efficacy trial. However, the double-blind study was terminated early because buprenorphine administered in combination with naloxone and buprenorphine administered alone were found to have greater efficacy than the placebo. The second part was an open-label safety phase lasting 48 weeks (for individuals who participated in the first part of the study) or 52 weeks (for individuals who did not participate in the first part). All study visits took place in a physician’s office in a clinical research program, which provided an environment that was distinct from the clinic where methadone is usually provided.

 

Participants were eligible for the study if they met the diagnostic criteria of opiate dependence according to the DSM–IV, were seeking opiate-substitution pharmacotherapy, were between the ages of 18 and 59 years, and could provide informed consent and comply with study procedures. Of the 451 individuals who were screened for the double-blind study, 323 were randomly assigned to one of three study groups:

 

·         Combination of buprenorphine and naloxone (n= 109)

·         Buprenorphine alone (n= 105)

·         Placebo (n= 109)

 

The group that received the buprenorphine and naloxone combination was 62.4 percent male and 59.5 percent white, 29.4 percent African American, 7.3 percent Hispanic, 1.8 percent Native American, and 1.8 percent Asian or Pacific Islander, with an average age of 38.1 years. The placebo group was 65.1 percent male and 64.2 percent white, 22.9 percent African American, 8.3 percent Hispanic, 1.8 percent Native American, and 2.8 percent Asian or Pacific Islander, with an average age of 38 years. There were no significant differences between the groups.

 

In addition to receiving medication treatment during the double-blind trial, all study participants received counseling regarding the human immunodeficiency virus (HIV) infection as well as 1 hour of individualized counseling per week. Emergency counseling (e.g., after a relapse) and referrals (e.g., to a community legal aid program) were also available to participants, but no other services were provided.

 

The open-label study included 461 participants (268 of whom had participated in the double-blind trial). Study participants were given buprenorphine alone for the first 2 days of treatment, after which they were given the combination of buprenorphine and naloxone. In addition to the medication, individual counseling was made available at the clinics, but participants were encouraged to obtain behavioral–treatment services outside the study.

 

The primary outcomes of interest in the double-blind trial were the percentage of opiate-negative urine samples and study participants’ self-reported craving for opiates. Urine samples were tested for opiates (morphine, codeine, and corresponding metabolites) as well as for other drugs of abuse (amphetamines, barbiturates, benzodiazepines, cocaine, and methadone). Participants’ retention in the study was also examined. The open-label phase looked at serious adverse effects and the percentage of urine samples negative for opiates, cocaine, and benzodiazepines. Urine samples were collected three times a week during the double-blind trial and two times a month during the open-label phase.

 

The primary comparisons were made between the treatment group that received buprenorphine in combination with naloxone and the placebo group. The group that received buprenorphine alone served as an active control. A two-factor (site and group) analysis of variance was used to analyze the percentage of urine opiate-negative urine samples. Least-square means analysis was used for each of the three pairwise combinations.

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Cost

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There is no cost information available for this program.
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Evidence-Base (Studies Reviewed)

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These sources were used in the development of the program profile:

Study 1
Krook, Aud L., Odd Brørs, Jannicke Dahlberg, Kirsten Grouff, P. Magnus, E. Røysamb, and Helge Waal. 2002. “A Placebo-Controlled Study of High Dose Buprenorphine in Opiate Dependents Waiting for Medication-Assisted Rehabilitation in Oslo, Norway.” Addiction 97:533–42.

Study 2
Fudala, Paul J., T. Peter Bridge, Susan Herbert, William O. Williford, C. Nora Chiang, Karen Jones, Joseph Collins, Dennis Raisch, Paul Casadonte, R. Jeffrey Goldsmith, Walter Ling, Usha Malkerneker, Laura McNicholas, John Renner, Susan Stine, and Donald Tusel. 2003. “Office-Based Treatment of Opiate Addiction with a Sublingual-Tablet Formulation of Buprenorphine and Naloxone.” New England Journal of Medicine 349(10):949–56.
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Additional References

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These sources were used in the development of the program profile:

Center for Substance Abuse Treatment. N.d. About Buprenorphine Therapy. Accessed May 13, 2011.
http://buprenorphine.samhsa.gov/about.html

Fischer, Gabriele, Wolfgang Gombas, Harald Eder, Reinhold Jagsch, Alexandra Peternell, Georg Stuchlinger, Lukas Pezawas, Harald N. Aschauer, and Siegfried Kasper. 1999. “Buprenorphine Versus Methadone Maintenance for the Treatment of Opioid Dependence.” Addiction 94(9):1337–47.

Johnson, Rolley E. 2000. “A Comparison of Levomethadyl Acetate, Buprenorphine, and Methadone for Opioid Dependence.” The New England Journal of Medicine 343:1290–97.

Katz, Elizabeth C., Robert P. Schwartz, Stuart King, David A. Highfield, Kevin E. O’Grady, Timothy Billings, Devang Gandhi, Eric Weintraub, David Glovinsky, Wardell Barksdale, and Barry S. Brown. 2009. “Brief Versus Extended Buprenorphine Detoxification in a Community Treatment Program: Engagement and Short-Term Outcomes.” American Journal of Drug and Alcohol Abuse 35:63–67.

Kinlock, Timothy W., Michael S. Gordon, Robert S. Schwartz, and Terrence T. Fitzgerald. 2010. “Developing and Implementing a New Prison-Based Buprenorphine Treatment Program.” Journal of Offender Rehabilitation 49:91–109.

Lintzeris, Nicholas, Alison Ritter, Mary Panjari, Nicholas Clark, Jozica Kutin, and Gabriele Bammer. 2004. “Implementing Buprenorphine Treatment in Community Settings in Australia: Experiences from the Buprenorphine Implementation Trial.” The American Journal on Addictions 13:S29–S41.

Mattick, R.P., J. Kimber, and M. Davoli. 2008. “Buprenorphine Maintenance Versus Placebo or Methadone Maintenance for Opioid Dependence (Review).” Cochrane Database of Systematic Reviewer, Issue 2.

Neri, S., C.M. Bruno, D. Pulvierenti, M. Malaguarnera, C. Italiano, B. Mauceri, G. Abate, D. Cilio, S. Calvagno, A. Tsami, L. Ignaccolo, D. Interlandi, L. Prestianni, M. Ricchena, and R. Noto. 2005. “Randomized Clinical Trial to Compare the Effects of Methadone and Buprenorphine on the Immune System in Drug Abusers.” Psychopharmacology 179:700–704.

Petitjean, Slyvie, Rudolf Stohler, Jean-Jacques Deglon, Santino Livoti, Doris Waldvogel, Claude Uehlinger, and Dieter Ladewig. 2001. “Double-Blind Randomized Trial of Buprenorphine and Methadone in Opiate Dependence.” Drug and Alcohol Dependence 62:97–104.

Schottenfeld, Richard S. 2005. “Methadone Versus Buprenorphine With Contingency Management or Performance Feedback for Cocaine and Opioid Dependence.” American Journal of Psychiatry 162:340–49.
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Related Practices

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Following are CrimeSolutions.gov-rated practices that are related to this program:

Opiate Maintenance Therapy for Dual Heroin–Cocaine Abusers
A medication-assisted treatment for opioid dependence, including methadone, buprenorphine, and Levo-Alpha-Acetymethadol (LAAM). The overall goals are to help opioid-addicted patients alleviate withdrawal symptoms, reduce or suppress opiate cravings, and reduce the illicit use of opioids (such as heroin). The practice is rated Effective for achieving higher sustained heroin abstinence for dual heroin–cocaine abusers, but No Effects for cocaine abstinence for dual abusers.

Evidence Ratings for Outcomes:
Effective - One Meta-Analysis Drugs & Substance Abuse - Heroin/opioids
No Effects - One Meta-Analysis Drugs & Substance Abuse - Cocaine/crack cocaine
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Program Snapshot

Age: 18 - 59

Gender: Both

Race/Ethnicity: Black, American Indians/Alaska Native, Asian/Pacific Islander, Hispanic, White

Geography: Suburban, Urban

Setting (Delivery): Inpatient/Outpatient, Other Community Setting

Program Type: Alcohol and Drug Therapy/Treatment, Individual Therapy

Targeted Population: Alcohol and Other Drug (AOD) Offenders

Current Program Status: Active