Clinical Question

Is buprenorphine maintenance treatment effective in the management of opioid use disorder?

Evidence-Based Answer

At dosages greater than 2 mg per day, buprenorphine maintains treatment retention better than placebo. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.) At 16 mg or more per day, buprenorphine was found to reduce illicit substance use compared with placebo as monitored by urinalysis. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

When flexible dosing (doses adjusted based on patient symptoms) is used, the effectiveness of buprenorphine is comparable to that of methadone in suppressing opioid use. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.) When fixed dosing (a set dose is given) of 7 mg or more is used, buprenorphine and methadone are equally effective as measured by retention in treatment and suppression of illicit opioid use. (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., combines “opioid abuse” and “opioid dependence” into the new diagnosis “opioid use disorder,” categorized as mild, moderate, or severe based on the number of positive symptoms.¹ Pharmacologic treatment options for opioid use disorder include methadone and buprenorphine. Buprenorphine is usually prescribed as a combination formulation that includes the pharmacologically inactive naloxone, except in pregnancy when it is recommended that buprenorphine be used alone. Both methadone and buprenorphine are intended to be administered in conjunction with psychosocial treatment, with the goal of eliminating withdrawal symptoms and maintaining the patient on a documented and regulated dosage. Because buprenorphine is a partial agonist, there is a ceiling effect to the level of respiratory depression or sedation it can cause, reducing the risk of overdose. Buprenorphine may be prescribed by primary care physicians who complete eight hours of training and receive a waiver from the Drug Enforcement Administration.

This analysis included 31 randomized controlled trials (5,430 participants) comparing buprenorphine maintenance with placebo or methadone maintenance. Primary outcomes were retention in treatment and continued use of opioids as measured by self-report or urinalysis. Various dosing regimens were used. All dosages of buprenorphine were superior to placebo in treatment retention: 7 to 15 mg per day (relative risk [RR] = 1.74; 95% confidence interval [CI], 1.06 to 2.87), and 16 mg or more per day (RR = 1.82; 95% CI, 1.15 to 2.90). Thus, given a baseline retention rate of 40% in those receiving placebo, the retention rate would increase to approximately 70% in those receiving 7 to 15 mg of buprenorphine and to 73% in those using at least 16 mg of buprenorphine daily. Only high-dosage buprenorphine (at least 16 mg per day) was effective—and then, only mildly—in suppressing illicit opioid use when monitored by urinalysis (standardized mean difference [SMD] = −1.17; 95% CI, −1.85 to −0.49).

In studies comparing buprenorphine maintenance with methadone maintenance, flexible dosing and fixed dosing were evaluated. In analyses of flexible dosing, buprenorphine was less effective than methadone in treatment retention (RR = 0.83; 95% CI, 0.72 to 0.95), but there was no difference between groups in suppression of opioid use when monitored by urinalysis (SMD = −0.11; 95% CI, −0.23 to 0.02). However, when fixed dosing was studied, medium (7 to 15 mg) and high (16 mg or more) doses of buprenorphine were found to be equivalent to medium (40 to 85 mg) and high (85 mg or more) fixed doses of methadone in terms of retention and suppression of illicit opioid use.

Two studies comparing buprenorphine and methadone found no difference in the frequency of adverse effects,^2,3 but one of the two reported an increased level of sedation in the methadone group (58% vs. 26%).³ A third study comparing buprenorphine with placebo reported that adverse effects were similar in the two groups.⁴

Clinical practice guidelines encourage the use of buprenorphine and methadone as medication-assisted treatments.^5,6 Both medications were given a level A rating, indicating that a strong level of evidence was found and that the intervention benefits substantially outweighed harms.⁶ Factors including availability of methadone facilities, a patient's ability to meet the requirements associated with a treatment program, the safety profiles of buprenorphine and methadone, and patient preference should be considered when helping patients determine which treatment option best fits their needs.