Question 19: How do buprenorphine and methadone compare?

Answer: Buprenorphine is approved for use in the treatment of opioid dependence in a large number of countries, including Australia, Belgium, Canada, Croatia, Germany, Iran, England, France, the United Kingdom, and the United States. Buprenorphine is a partial agonist at the opioid receptor, as opposed to a full agonist such as methadone or heroin. This means that buprenorphine has a unique pharmacologic profile leading to a lower likelihood of overdose or respiratory depression. Like methadone, buprenorphine has the ability to suppress opioid craving and withdrawal, block the effects of self-administered opioids, retain patients in treatment, and decrease illicit opioid use. Because it is a partial agonist, buprenorphine maintains patients in a milder degree of physical dependence and is associated with milder withdrawal syndrome following cessation.

Clinical trials comparing the efficacy of buprenorphine to methadone on the outcomes of retention and illicit opioid use have demonstrated similar results when compared with low doses of methadone (20 to 30 mg) (Kosten, Schottenfeld, Ziedonis, et al., 1993).

Figure 37a illustrates a meta-analysis of 13 clinical trials that compared buprenorphine maintenance with methadone maintenance had the following findings: “Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patients in treatment (RR = 0.82; 95% CI: 0.69-0.96). Low-dose buprenorphine is not superior to low-dose methadone. High-dose buprenorphine does not retain more patients than low-dose methadone, but may suppress heroin use better. There was no advantage for high-dose buprenorphine over high-dose methadone in retention (RR = 0.79; 95% CI: 0.62-1.01), and high-dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR = 1.24; 95% CI: 1.06-1.45), high doses (RR = 1.21; 95% CI: 1.02-1.44), and very high doses (RR = 1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.” (Mattick, Kimber, Breen, et al., 2003).

Figure 37a

Figure 37b illustrates a meta-analysis of 13 clinical trials that compared buprenorphine maintenance with methadone maintenance had the following findings: “Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patients in treatment (RR = 0.82; 95% CI: 0.69-0.96). Low-dose buprenorphine is not superior to low-dose methadone. High-dose buprenorphine does not retain more patients than low-dose methadone, but may suppress heroin use better. There was no advantage for high-dose buprenorphine over high-dose methadone in retention (RR = 0.79; 95% CI: 0.62-1.01), and high-dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR = 1.24; 95% CI: 1.06-1.45), high doses (RR = 1.21; 95% CI: 1.02-1.44), and very high doses (RR = 1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.” (Mattick, Kimber, Breen, et al., 2003).

Figure 37b

Figures 37a and 37b illustrate that a meta-analysis of 13 clinical trials that compared buprenorphine maintenance with methadone maintenance had the following findings: “Buprenorphine given in flexible doses appeared statistically significantly less effective than methadone in retaining patients in treatment (RR = 0.82; 95% CI: 0.69-0.96). Low-dose buprenorphine is not superior to low-dose methadone. High-dose buprenorphine does not retain more patients than low-dose methadone, but may suppress heroin use better. There was no advantage for high-dose buprenorphine over high-dose methadone in retention (RR = 0.79; 95% CI: 0.62-1.01), and high-dose buprenorphine was inferior in suppression of heroin use. Buprenorphine was statistically significantly superior to placebo medication in retention of patients in treatment at low doses (RR = 1.24; 95% CI: 1.06-1.45), high doses (RR = 1.21; 95% CI: 1.02-1.44), and very high doses (RR = 1.52; 95% CI: 1.23-1.88). However, only high and very high dose buprenorphine suppressed heroin use significantly above placebo.” (Mattick, Kimber, Breen, et al., 2003.) (This review will be updated.)

 

Patients receiving buprenorphine can be either (1) discontinued without significant withdrawal, (2) maintained, or (3) transferred to opioid antagonist treatment, such as naltrexone. Patients with a higher level of physical dependence and whose needs cannot be met by buprenorphine can be transferred to an opioid agonist, such as methadone or L-alpha-acetyl-methadol (LAAM).

Research Highlights

  • Mello and Mendelson showed that buprenorphine suppresses heroin self-administration by opioid-dependent primates and humans (Mello, Bree, and Mendelson, 1983).
  • Findings from a subsequent dose-ranging study at the Los Angeles Addiction Treatment Research Center (LAATRC) suggest that the median doses of buprenorphine for adequate clinical stabilization may be in the 12- to 16-mg range (Compton, Ling, Charuvastra, et al., in press).
  • A NIDA-sponsored, 12-site LAATRC/Veterans Administration/NIDA multicenter study compared doses of 1, 4, 8, and 16 mg of buprenorphine in 631 patients. The primary comparison between the 8-mg and the 1-mg groups shows that the 8-mg group used fewer illicit opioids and remained in treatment longer (Ling, Charvastra, Collins, et al., 1998).

    A clinical trial comparing buprenorphine, the buprenorphine/naloxone combination, and placebo was terminated early because buprenorphine and naloxone in combination and buprenorphine alone were found to have greater efficacy than placebo. Opioid-negative urine samples were found more frequently in the buprenorphine and buprenorphine/naloxone groups (17.8% and 20.7%, respectively) than in the placebo group (5.8%, p < 0.001 for both comparisons) (Fudala, Bridge, Herbert, et al., 2003).

Potential Benefits of Buprenorphine

Research on buprenorphine has shown that it has the potential to be a feasible alternative to methadone maintenance treatment. One potential benefit of buprenorphine compared with methadone that needs further investigation is a lower prevalence of medication interactions between buprenorphine and highly active antiretroviral treatment used to treat patients with HIV (

Figure 38 illustrates the potential benefits of buprenorphine.

Figure 38 illustrates the potential benefits of buprenorphine.

 

References

Compton P, Ling W, Charuvastra C, Wesson DR. Buprenorphine as a pharmacotherapy for opioid addiction: what dose provides a therapeutic response? American Journal of the Addictions, in press.

Fudala PJ, Bridge TP, Herbert S, Williford WO, Chiang CN, Jones K, et al. Buprenorphine/Naloxone Collaborative Study Group. Office-based treatment of opiate addiction with a sublingual-tablet formulation of buprenorphine and naloxone. New England Journal of Medicine 2003;349(10):949-58.

Johnson RE, Jaffe JH, Fudala JP. A controlled trial of buprenorphine treatment for opioid dependence. JAMA1992;267(20):2750-55.

Kosten TR, Schottenfeld R, Ziedonis D, Falcioni J. Buprenorphine versus methadone maintenance for opioid dependence. Journal of Nervous and Mental Disease 1993;181(6):358-64.

Ling W, Charuvastra C, Collins JF, Batki S, Brown LS, Kintaudi P, et al. Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 1998;93(4):475-86.

Ling W, Wesson DR, Charuvastra C, Klett CJ. A controlled trial comparing buprenorphine and methadone maintenance in opioid dependence. Archives of General Psychiatry 1996;53(5):401-47.

Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. The Cochrane Database of Systematic Reviews, Issue 2, 2003.

Mello NK, Bree MP, Mendelson JH. Comparison of buprenorphine and methadone effects on opioid self-administration in primates. Journal of Pharmacological Experimental Therapy 1983;225:378-86.

Mello NK, Mendelson JH. Buprenorphine suppresses heroin use by heroin addicts. Science 1980;27:657-59.

Mello NK, Mendelson JH, Kuehnle JC. Buprenorphine effects on human heroin self-administration: an operant analysis. Journal of Pharmacological Experimental Therapy 1982;223:30-39.

Strain EC, Stitzer ML, Liebson IA, Bigelow GE. Buprenorphine versus methadone in the treatment of opioid-dependent cocaine users. Psychopharmacology (Berl) 1994;116(4):401-06.

Sullivan LE, Fiellin DA. Buprenorphine: its role in preventing HIV transmission and improving the care of HIV infected patients with opioid dependence. Clinical Infectious Diseases 2005;41(6):891-96