Medication-Assisted Treatment With Buprenorphine: Assessing the Evidence
Abstract
Objective
Methods
Results
Conclusions
About the AEB Series
Feature | Description |
---|---|
Service definition | Medication-assisted treatment is a direct service that provides a person with a substance use or mental disorder with pharmacotherapy in conjunction with behavioral therapies as treatment for associated symptoms or disabilities. The nature of the services provided is determined by the person’s current status or needs.Buprenorphine maintenance therapy is a medication-assisted treatment that uses buprenorphine or buprenorphine-naloxone to help individuals with an opioid use disorder abstain from or decrease the use of illegal opioids (for example, intravenous heroin) or the use of opioids in a nonprescribed manner (for example, abuse of prescription pain medications). |
Service goals | Retention in treatment; decrease in illegal opioid use; decrease in mortality; decrease in nonopioid drug use; decrease in criminal activity; decrease in risk behaviors related to HIV and hepatitis C |
Populations | Adults with opioid use disorders; pregnant women with opioid use disorders |
Settings of service delivery | Office-based facilities; opioid treatment centers |
Description of BMT
Methods
Search strategy
Inclusion and exclusion criteria
Strength of the evidence
Effectiveness of the service
Results and discussion
Level of evidence
Study | Design and objectives | Population and conditions | Outcomes measured | Summary of findings |
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Johnson et al., 1995 (18) | RCT to assess early clinical effectiveness of buprenorphine versus placebo in an opioid-dependent population | Patients randomly assigned to placebo (N=60) or to 2 mg (N=60) or 8 mg (N=30) daily of sublingual buprenorphine. On days 6–13, patients could request a dose change, knowing that the new dose would be randomly chosen from the 2 other alternatives. | Primary: percentage of patients in each group requesting a dose change. Secondary: positive urine opioid screens and patient satisfaction with treatment | Significant main effect of buprenorphine versus placebo. Patients taking buprenorphine requested fewer dose changes (27% for 2 mg and 32% for 8 mg versus 65% for placebo, p<.01). They also had fewer positive urine drug screens (p<.05) and rated dose adequacy higher (p<.01). Effects were significant for buprenorphine versus placebo but not for various doses. |
Ling et al., 1996 (19) | RCT to evaluate safety and efficacy of long-term, fixed-dose BMT versus low- and high-dose MMT | 225 treatment-seeking patients with opioid dependence randomly assigned to receive 8 mg per day of buprenorphine, 30 mg per day of methadone (low dose), or 80 mg of MMT (high dose), all over a 1-year period | Primary: urine toxicology, retention, craving, and withdrawal symptoms; safety data | At 26 and 52 weeks, the high-dose MMT group had better retention (31% versus 20% at 52 weeks, p=.009) and less opioid use (p=.002) than the low-dose MMT or fixed-dose BMT groups. Results were comparable in the latter two groups. No serious adverse health effects were noted for 8 mg of buprenorphine. |
Ling et al., 1998 (16) | RCT to evaluate safety and efficacy of an 8 mg per day sublingual dose of buprenorphine versus a 1 mg per day dose over a 16-week treatment period in a heroin-dependent population; secondary analysis of 2 other dose levels (4 mg and 16 mg) | 736 total patients in 4 dose groups: 1 mg, N=185; 4 mg, N=182; 8 mg, N=188; and 16 mg, N=181. Total of 375 completed the full 16 treatment weeks. | Primary: retention in treatment, illicit opioid use as indicated by urine drug screens, opioid craving, and global ratings | For retention, 40% in 1-mg group completed treatment, 51% in 4-mg group, 52% in 8-mg group, and 61% in 16-mg group. The 1-mg group had poorer retention than the 8-mg (p=.019) or 16-mg (p<.001) groups. The 8-mg group had significantly fewer positive screens than the 1-mg group, less craving, and higher global ratings (p<.05). |
O’Connor et al., 1998 (25) | RCT to evaluate the effect of thrice weekly BMT in a primary care setting versus a traditional treatment facility | 46 patients assigned to primary care treatment (N=23) or traditional treatment setting (N=23) for 12 weeks | Primary: treatment retention and urine drug tests | A trend toward higher retention at 12 weeks was noted in the primary care setting (78% versus 52%, p=.06). Patients in that setting had significantly lower rates of illicit opioid use as measured by urine drug tests (63% versus 85%, p<.01) but no difference in rates of cocaine use. |
Johnson et al., 2000 (20) | RCT to compare levomethadyl acetate (75–115 mg), buprenorphine (16–32 mg), and high-dose (60–100 mg) and low-dose (20 mg) methadone as treatments for opioid dependence | 220 patients, with 55 in each group; 51% completed the 17-week trial. | Primary: treatment retention, opioid use (percentage of positive urine screens), degree of continuous abstinence from opioid use (at least 12 consecutive opioid-free urine screens), and patients’ reports of use. Secondary: percentage of cocaine-positive urine screens, abstinence from cocaine use, breath alcohol readings, side effects, and sex-related differences | No difference was found between high-dose buprenorphine and high-dose methadone in days in treatment (mean of 96 and 105 days, respectively) or percentage of patients with 12 or more consecutive negative screens (26% versus 28%, respectively). High-dose buprenorphine was superior to low-dose methadone for both outcomes (mean days, 96 versus 70, p<.001; consecutive negative screens, 26% versus 8%, p=.005). |
Fudala et al., 2003 (17) | RCT to compare 4 weeks of office-based treatment with daily sublingual tablets of buprenorphine (16 mg) in combination with naloxone (4 mg), buprenorphine alone (16 mg), or placebo for patients addicted to opioids | 323 patients receiving at least one dose of study medication; 109 randomly assigned to the combination medication, 105 to buprenorphine alone, and 109 to placebo | Primary: percentage of urine screens negative for opiates and self-reported craving for opiates by patients | During each of the 4 weeks, mean craving scores in the combined and buprenorphine groups were significantly lower than in the placebo group (p<.001 for both). Both groups with buprenorphine-based treatments had reduced opioid use. Opioid-negative screens: combined group, 17.8%; buprenorphine group, 20.7%; and placebo group, 5.8% (p<.001 for all) |
Kakko et al., 2003 (15) | RCT to compare daily buprenorphine (fixed dose) versus a 6-day tapered regimen of buprenorphine followed by placebo; 12-month program combined with psychotherapy | 40 patients randomly assigned to fixed-dose buprenorphine (N=20) or the tapered regimen (N=20) | Primary: 1-year retention in treatment and negative urine drug screens | One-year retention was 75% in the buprenorphine group and 0% in the placebo group (p=.001). Roughly 75% of the patients retained in treatment had negative urine screens for illicit opiates, stimulants, cannabinoids, and benzodiazepines. |
Jones et al., 2005 (28) | RCT to compare NAS among neonates of MMT- and BMT-maintained pregnant, opioid-dependent women; provide preliminary safety and efficacy data | 30 patients randomly assigned to MMT (N=15) or to BMT (N=15); 11 and 9, respectively, completed the study. | Primary: number of neonates treated for NAS, amount of medication used to treat NAS, length of neonatal hospitalization, and peak NAS score. Secondary: treatment retention and illicit opiate use | No significant difference in illicit opioid use between groups. Total of 20.0% and 45.5% of BMT-exposed and MMT-exposed neonates, respectively, were treated for NAS (p=.23). Other primary outcomes were also not significantly different, except that the BMT-exposed neonates had a shorter average hospital stay (p=.021). |
Fischer et al., 2006 (29) | RCT to evaluate the efficacy and safety of MMT versus BMT for pregnant, opioid-dependent women | 18 pregnant women randomly assigned to receive MMT (N=9) or BMT (N=9) during weeks 24–29 of pregnancy. After dropout, data were available from 14 cases (6 for methadone and 8 for buprenorphine. | Primary for mothers: treatment retention, urine drug screens, and nicotine use. Primary for neonates: routine birth data and severity and duration of NAS | For mothers, no significant difference in retention was found between groups. MMT group had significantly less use of additional opioids (p=.029). For neonates, earlier onset of NAS was noted in the MMT group; 43% of neonates n both groups combined did not require NAS treatment. Duration of NAS treatment was short in both groups (mean 5 days). |
Kakko et al., 2007 (24) | RCT to compare adaptive, BMT stepped care versus optimal MMT | 96 patients randomly assigned to flexible-dose MMT group (N=48) or BMT stepped-care group (N=48). In stepped treatment, buprenorphine could be increased to 32 mg. If participants required additional medication, they were switched (stepped) to high-dose methadone. | Primary: 6-month treatment retention, negative urine opioid screens, and problem severity | No differences between groups were found for retention (76% for both at 6 months) or the proportion of negative screens (80% for both groups). For the BMT stepped-care group, 17 completers did not switch to methadone and finished with a mean buprenorphine dose of 29.6 mg, and 20 completers switched to methadone and completed with a mean methadone dose of 111 mg. Methadone group ended with a mean dose of 110 mg. |
Comer et al., 2010 (31) | Randomized cross-over study to assess intravenous abuse potential of buprenorphine-naloxone compared with buprenorphine among injection drug users receiving BMT | 12 intravenous drug users living in a hospital for 8–9 weeks and receiving buprenorphine-naloxone under 3 BMT dose conditions: 2 mg, 8 mg, and 24 mg | Primary: reinforcing effects of intravenous buprenorphine-naloxone and buprenorphine among BMT-maintained intravenous drug users who were given a drug-versus-money choice exercise | Buprenorphine-naloxone intravenous abuse potential was lower than buprenorphine alone or heroin, particularly on higher maintenance doses. Intravenous buprenorphine-naloxone was self-administered less frequently than buprenorphine or heroin (p<.001). Selective ratings for “drug liking” and “desire to take the drug again” were lower for buprenorphine-naloxone than for buprenorphine alone or heroin (p=.001). |
Jones et al., 2010 (27) | RCT to examine neurobehavioral effects for neonates exposed to MMT or BMT | 175 pregnant women with opioid dependency assigned to MMT group (N=89) or BMT group (N=86) | Primary: reduction in opioid use, treatment retention, percentage of neonates treated for NAS, NAS peak score, length of hospital stay, morphine required to treat NAS | Treatment was discontinued by 18% of women in the MMT group and 33% in the BMT group; 58 mothers exposed to buprenorphine and 73 exposed to methadone were followed to the end of pregnancy. Neonates of the former group required less morphine (mean dose, 1.1 versus 10.4 mg, p<.009), had a shorter hospital stay (10.0 versus 17.5 days, p<.009), and had a shorter duration of NAS treatment (4.1 versus 9.9 days, p<.003). |
Ling et al., 2010 (21) | RCT to determine efficacy of buprenorphine implants (6 month) versus placebo | 163 patients received buprenorphine implants (N=108) or placebo implants (N=55) after induction with sublingual buprenorphine tablets | Primary: treatment retention and reduction in illicit opioid use as measured by urine drug screens. Secondary: drug craving and withdrawal symptoms | Significantly more patients with buprenorphine implants completed the study (65.7% versus 30.9%, p<.001). The buprenorphine group had more negative screens (40.4% versus 28.3%, p=.04), reduced withdrawal symptoms on the Clinical Opiate Withdrawal Scale (p<.001), and the Subjective Opiate Withdrawal Scale (p=.004), lower patient ratings for craving on the Visual Analog Scale–opioid craving (p<.001), fewer symptoms on the Clinical Global Impressions–Severity Scale (34.9% versus 19.1% with no symptoms, p<.001), and greater change on the Clinical Global Impressions–Improvement Scale (56.0% versus 23.4% reporting very much improvement at week 24, p<.001). |
Lucas et al., 2010 (26) | RCT to compare clinic-based BMT with case management and referral and an opioid treatment program within an HIV clinic | 93 HIV-positive, opioid-dependent patients not receiving opioid agonist therapy and not dependent on alcohol or benzodiazepines randomly assigned to receive BMT in an HIV clinic (N=46) or referred to an opioid treatment program, where they received either buprenorphine or methadone (N=47) | Primary: initiation and long-term treatment with opioid agonist therapy, urine screen results, visit attendance with primary HIV providers, use of antiretroviral therapy, and HIV treatment outcomes | A larger proportion of HIV clinic patients were on agonist therapy at 12 months (74% versus 41%; p<.001). Illicit opioid use was less in the clinic-based group (44% versus 65%; p=.015). HIV clinic patients had significantly fewer cocaine-positive screens and attended more HIV primary care visits. No difference was found in use of antiretroviral therapy or in improvements in HIV-monitoring tests. |
Bazazi et al., 2011 (32) | Self-administered survey study to examine use, procurement, and motivations for use of diverted buprenorphine-naloxone | 100 opioid users; 51 injecting users and 49 noninjecting users | Primary: illicit possession of buprenorphine-naloxone, use of diverted buprenorphine-naloxone, reasons for use, and use to “get high” | More noninjecting users reported ever using buprenorphine-naloxone to “get high” (69% versus 32%, p<.01). Most participants reporting past use of buprenorphine-naloxone stated that use was to treat withdrawal symptoms (74%) or to stop using other opioids (66%) or because they could not afford drug treatment (64%). |
Weiss et al., 2011 (22) | Multiphase RCT to evaluate efficacy of brief and extended buprenorphine-naloxone treatment with various counseling intensities | First phase (N=653): brief treatment with buprenorphine-naloxone with a 2-week stabilization, 2-week taper, and 8-week postmedication follow-up. Patients entered the second phase if they had opioid-positive urine samples during the first phase. Second phase (N=360): 12 weeks of buprenorphine-naloxone treatment, 4-week taper, and 8-week postmedication follow-up. In both phases, patients were randomly assigned to receive standard (15-minute medical visits) or enhanced medical management (standard medical management plus opioid dependence counseling during 45-minute visits). | Primary: minimal or no opioid use as measured by urine samples that confirmed self-reports | All urine samples were negative after the first phase for only 6.6% of patients. During extended treatment with buprenorphine-naloxone, 49.2% of patients had successful outcomes (opioid-negative urine samples); this rate fell to 8.6% at 8-week follow-up. Addition of counseling had no effect in either phase. |
Coyle et al., 2012 (30) | RCT to determine impact on infant neurobehavior of in-utero exposure to buprenorphine or methadone | 39 full-term infants exposed to methadone (N=21) or buprenorphine (N=18) | Primary: neonatal neurobehavioral effects, measured on the neonatal intensive care unit’s Network Neurobehavioral Scale | Infants exposed to buprenorphine exhibited fewer signs of stress abstinence (p<.001) and were less excitable (p<.001), less overaroused (p<.01), less hypertonic (p<.007), and better self-regulated (p<.04). |
Moore et al., 2012 (23) | RCT to investigate impact of directly observed therapy plus cognitive-behavioral therapy versus usual treatment among patients receiving BMT for 12 weeks in primary care | 55 opioid-dependent patients assigned to physician management with weekly buprenorphine dispensing (N=28) or with directly observed, thrice-weekly buprenorphine and cognitive-behavioral therapy (N=27) | Primary: treatment retention and drug use as measured by self-reports or urine screens | No difference was found between groups in treatment retention or drug use. |
Pritham et al., 2012 (33) | Retrospective descriptive study to examine opioid replacement treatment in pregnancy and effect on neonatal outcomes | 152 opioid-dependent pregnant women receiving MMT (N=136) or BMT (N=16) during pregnancy and their neonates | Primary: length of hospital stay for NAS | Neonates with prenatal exposure to MMT spent more days in the hospital for NAS (21 versus 14 days) (p=.05). |
Study | Focus of review | Population and conditions | Outcomes measured | Summary of findings |
---|---|---|---|---|
Barnett et al., 2001 (36) | Compare the effectiveness of buprenorphine and of methadone | Patients receiving methadone at medium-high (50–80 mg) and low (20–35 mg) doses and buprenorphine at medium doses (6–12 mg) across 5 RCTs | Primary: retention in treatment and urine drug screens for opioids | Compared with patients on medium-high methadone doses, those on medium doses of buprenorphine had 1.26 times the relative risk (RR) of discontinuing treatment (p=.019), and the rate of positive drug screens was 8.3% higher (p=.002). Buprenorphine was more effective than low doses of methadone in treatment retention (RR of discontinuing treatment=.86; ns) and reduction of positive drug screens (8.4% fewer, p<.05). |
Mattick et al., 2008 (34) | Compare the effects of BMT with placebo and MMT on treatment retention and suppression of illicit drug use | Evaluated 24 RCTs involving 4,497 patients | Primary: retention in treatment and illicit drug use suppression | Treatment retention was higher with BMT compared with placebo at low doses (RR=1.50, p<.05), medium doses (RR=1.74, p<.05), and high doses (RR=1.74, p<.05). |
McCance-Katz et al., 2010 (38) | Examine literature on methadone and buprenorphine for drug interactions with concurrent medications | Populations varied; extensive literature review with 93 references | Primary: drug interactions with methadone or buprenorphine | Buprenorphine had fewer drug interactions than methadone, especially with HIV medications. |
Amato et al., 2011 (37) | Evaluate the effectiveness of any psychosocial treatment plus any agonist maintenance treatment versus standard agonist treatment | 4,319 patients in 35 studies | Primary: retention in treatment and opiate abstinence; secondary: treatment compliance, psychiatric symptoms, depression, and death | Adding any psychosocial support to standard maintenance treatments did not appear to give additional benefits. |
Martin et al., 2011 (10) | Examine literature, regulatory actions, professional guidance, and opioid treatment program experiences regarding adverse cardiac events associated with methadone | Populations varied; extensive literature review with 108 references and input from panel and field experts | Primary: cardiac events associated with methadone; impact on cardiac QT interval | The pharmacology of buprenorphine affords it a better safety profile than methadone; buprenorphine (at standard doses) did not affect cardiac electrophysiology by lengthening the cardiac QT interval. |
Fareed et al., 2012 (35) | Meta-analysis to provide information about proper dosing in BMT to improve treatment outcomes | Compared higher doses of buprenorphine (16–32 mg per day) to lower dose (<16 mg per day) across 21 RCTs involving 2,703 patients | Primary: treatment retention and reduction in opioid use | Higher doses of buprenorphine were associated with better treatment retention than the lower dose (69% versus 51%, p=.006). |
Jones et al., 2012 (39) | Review literature on outcomes after maternal treatment with buprenorphine | Evaluated outcomes of 3 RCTs and 44 nonrandomized studies | Primary: fetal effects, neonatal effects, effects on breast milk, and longer-term developmental effects | Maternal treatment with buprenorphine had similar efficacy to methadone. Prenatal buprenorphine treatment resulted in less severe neonatal abstinence syndrome than methadone treatment. No adverse effects on infant development of in-utero buprenorphine exposure were found. Dose increases for methadone and buprenorphine may be needed during pregnancy. |
Effectiveness of BMT
Buprenorphine versus placebo.
Illicit use of buprenorphine.
Prescription opioid dependence.
Psychosocial interventions and support services
BMT versus MMT.
Treatment setting.
Buprenorphine use in pregnancy.
Conclusions
Evidence for the effectiveness of BMT: high
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Cover: Snowbound, by N. C. Wyeth, 1928. © Copyright 2014 National Museum of American Illustration™, Newport, Rhode Island. Photo courtesy Archives of the American Illustrators Gallery™, New York.
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