Keeping OTP Patients in Treatment Longer: Methadone vs. Buprenorphine

hour glass1Data from the first large randomized U.S. trial comparing treatment retention of methadone and buprenorphine patients confirm what a Cochrane review—generally considered the Gold Standard—and other studies have found: treatment retention is much higher with methadone than with buprenorphine, although  the two are equally effective in suppressing illicit opioid use.

The current study is actually a secondary analysis, using data from a large, multisite, open-label study assessing liver function in individuals treated for opioid dependence. The original study enrolled participants from nine opioid treatment programs (OTPs) between 2006 and 2009, randomized to receive either methadone or buprenorphine (as buprenorphine/naloxone). Buprenorphine patients in that study were more than 50 percent less likely than methadone patients to remain in treatment for 24 weeks.

The data were gathered from 529 methadone and 738 buprenorphine patients. (Investigators changed the original 1:1 ratio to 2:1 because of a higher number of buprenorphine dropouts.) Measurements included patient characteristics at baseline, medication dose and urine drug screens at baseline and weekly, days in treatment, and treatment completion.

The goal of the study was to examine patient and medication characteristics associated with treatment retention and continued illicit opioid use in patients given methadone vs. buprenorphine/naloxone.

Study Group

  • Average age 37 years; two-thirds were male
  • 71% white, 12% Hispanic, 9% African American
  • About 90% smoked cigarettes, 27% used alcohol, 69% had injected drugs during the previous 30 days
  • Positive test results for drugs other than opioids: cocaine, 37%; amphetamine, 9%; marijuana, 24%

Patients were told to abstain from opioids for 12 to 24 hours before study onset, to achieve mild-to-moderate opioid withdrawal.

Key Findings

  • Significantly more buprenorphine patients than methadone patients (25% vs. 8%) dropped out within the first 30 days
  • Significantly more methadone than buprenorphine patients completed treatment (74% vs. 46%)
  • Completion rate was even higher with higher daily doses
    • For methadone: 80% or higher with 60 mg or more; 91% or higher with 120 mg or more
    • For buprenorphine (which showed a linear dose-relationship): 60% with 30 to 32 mg, the study maximum
    • Factors associated with higher dropout rates included being younger, being Hispanic (relative to white), and using heroin, cannabinoids, cocaine, or amphetamine during treatment
    • Higher medication dose was related to lower opiate use, especially in the buprenorphine group

Average maximum daily doses for methadone were 93.1 mg (range, 5 to 397 mg), and for buprenorphine, 22.1 mg (range, 2 to 32 mg).

Investigators noted three important findings about buprenorphine retention:

  • About 25% of buprenorphine patients dropped out during the first 30 days, “suggesting a critical period calling for special efforts in retaining these participants”
  • During the first 9 weeks, positive opiate urine results were significantly lower among those receiving buprenorphine, confirming the drug’s advantage of a much shorter induction time
  • A linear positive relationship between dose and treatment completion rate suggested “the benefit of dosing greater than the common practice of a maximum dose of 16 mg”

Buprenorphine Doses and Treatment Outcomes

Even patients taking 30 to 32 mg buprenorphine daily, the maximum for this study, had a retention rate lower than the methadone group (60 percent vs. 74 percent), and about 30 percent continued opioid use. “These findings suggest that participants may yet fare better with [buprenorphine] doses higher than the 32 mg used in this study,” the authors said. They commented on the generally high safety profile of buprenorphine: “We believe with proper monitoring safety will not be a clinical concern in such an effort.”

The authors cited a large investigation (Di Petta) linking daily buprenorphine doses as high as 56 mg with a retention rate of over 92 percent at 30 months. They also drew a comparison to the previous long-standing practice of limiting daily methadone doses to 40 mg—later shown to be highly inadequate, with most patients needing 60 to 120 mg or more.

(Although many sources cite a maximum daily dose of 32/8 mg buprenorphine/naloxone, this is not the first clinical study to investigate higher doses. Studies such as this are based on clinical evidence, designed with safety checks in place, and approved by an institutional review board.)

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Hser YI, Saxon AJ, Huang D, et al. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi-site trial. [Epub ahead of print August 20, 2013.]  Addiction. doi: 10.1111/add.12333.


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Kakko J, Grönbladh L, Dybrandt Svanborg K, et al. A stepped care strategy using buprenorphine and methadone versus conventional methadone maintenance in heroin dependence: a randomized controlled trial. Am J Psychiatry. 2007;164:797-803. doi:10.1176/appi.ajp.164.5.797.

Mattick RP, Kimber J, Breen C, Davoil M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2008;16(2):CD002207. doi: 10.1002/14651858.CD002207.pub3.

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