Department of Pharmacy Practice, College of Pharmacy (Drs. Posen, Keller, Elmes, and Jarrett) and Department of Academic Internal Medicine (Dr. Messmer) and Department of Family and Community Medicine (Drs. Gastala and Neeb), College of Medicine, University of Illinois Chicago jarrett8@uic.edu
Drs. Posen, Keller, Elmes, Messmer, Gastala, and Neeb reported no potential conflict of interest relevant to this article. Dr. Jarrett is a consultant to Trevena, developer of an investigative agent, TRV734, for medication-assisted treatment of opioid use disorder. She receives research funding from the US Health Resources and Services Administration; the Illinois Department of Human Services; the Substance Abuse and Mental Health Services Administration of the US Department of Health and Human Services; the Gordon and Betty Moore Foundation; and the Coleman Foundation.
Clinical considerations. Methadone requires slow titration. For patients starting methadone as an outpatient, federal law15 limits the initial dose to 30 mg and requires physician documentation when the first-day total dosage exceeds 40 mg. This dosing constraint makes it challenging to provide care because a daily dosage ≥ 60 mg has been found to produce, first, higher program retention (relative risk = 1.36; 95% CI, 1.13-1.63) and, second, greater reduction in illicit opioid use (relative risk = 1.59; 95% CI, 1.16-2.18) than is seen in patients who receive a lower daily dosage.16
Due to a prolonged elimination half-life, methadone reaches steady-state in 3 to 5 days. Patients and their families should be educated that withdrawal symptoms might not feel fully managed in the first few days of therapy and that time is required to experience safely the regimen’s full effects.
Aggressive dose-titration during methadone induction can result in drug accumulation and respiratory depression. The risk for methadone-related mortality is highest in the first 2 weeks of therapy, mostly related to overdose potential if the drug is combined with other opioids.17
Buprenorphine
Background. The prescribing rate for buprenorphine, particularly in primary care, is accelerating.18 A meta-analysis of randomized controlled trials found that11:
compared to placebo, buprenorphine, at any dosage, improves treatment retention by an absolute 21% to 28% (NNT = 4-5)
patients receiving high-dose buprenorphine (≥ 16 mg/d) had fewer evident cases of illicit opioid use.
Unlike methadone, buprenorphine exerts partial agonism at the μ-opioid receptor, resulting in a so-called ceiling effect that significantly reduces the adverse effect profile, including respiratory depression and euphoria, relative to a full-agonist opioid, such as methadone.19
