Opioid Use Disorder is a medical condition characterized by compulsive opioid use and persistent neurobiological changes that perpetuate dependence. Pharmacotherapy is central to effective treatment and reduces relapse, overdose, and mortality. The three medications approved by the U.S. Food and Drug Administration (FDA) for maintenance treatment of opioid use disorder—methadone, buprenorphine, and naltrexone—each have different mechanisms, dosing regimens, and tapering approaches, but they all aim to achieve physiological stability and long-term recovery (1).
Methadone, a full μ-opioid receptor agonist, suppresses withdrawal symptoms and cravings by providing continuous receptor activation. It is dispensed through certified treatment programs to ensure supervision and reduce diversion. Treatment typically begins with a dose of 10–30 mg once daily. If withdrawal symptoms persist, the dose can be adjusted in increments of 5–10 mg. Maintenance doses generally range from 60 to 120 mg per day, titrated to control withdrawal symptoms without causing excessive sedation. Once patients achieve stability and sustained remission, gradual tapering is recommended. This typically involves reducing the dose by 5–10% every one to two weeks (2). Taper periods shorter than several months frequently precipitate withdrawal and relapse. Although methadone carries risks of QT interval prolongation, constipation, and respiratory depression, it remains the most effective option for patients with severe or long-term opioid dependence (1).
Buprenorphine is a partial μ-opioid receptor agonist and kappa-opioid receptor antagonist with a ceiling effect that limits respiratory depression. Its favorable safety profile enables its use in office-based settings, thereby expanding access to treatment. Buprenorphine should be started once early withdrawal symptoms appear, which is typically 12–24 hours after the last use of a short-acting opioid, to avoid full withdrawal. The initial dose of this medication is 2–4 mg sublingually and is titrated up to the usual maintenance range of 8–24 mg daily (3). Buprenorphine combined with naloxone is preferred to reduce the risk of misuse by injection. When discontinuing therapy, the dose can be tapered by 2 mg every one to two weeks. Withdrawal symptoms, such as anxiety and insomnia, are usually mild. The balance of efficacy, safety, and accessibility that buprenorphine offers makes it a leading first-line medication for most patients receiving treatment for opioid use disorder (2).
Naltrexone, a competitive opioid receptor antagonist, blocks the euphoric effects of opioids without causing dependence. It is administered orally once daily in 50 mg doses or as an intramuscular injection of 380 mg every four weeks. However, because it can trigger withdrawal in opioid-dependent individuals, initiation must follow a period of 7–10 days without short-acting opioids or 10–14 days without methadone (4). Naltrexone does not require tapering upon discontinuation. However, adherence is often limited, and patients who stop taking the medication are at high risk of overdose if they relapse due to diminished tolerance (5).
Decisions about tapering should be made on an individual basis and guided by the patient’s medical stability, motivation, and available psychosocial support. Abrupt discontinuation or rapid dose reduction often results in significant withdrawal symptoms and cravings, which increases the likelihood of relapse. Therefore, a gradual, flexible taper adjusted to the patient’s tolerance and clinical response is generally preferred. Evidence suggests that maintaining pharmacotherapy for at least a year before tapering improves treatment retention and long-term recovery outcomes. Supportive medications, including clonidine, hydroxyzine, and non-opioid analgesics, can alleviate withdrawal-related discomfort and facilitate a smoother transition during dose reduction, improving outcomes for patients with opioid use disorder (1).
References
- Buresh M, Stern R, Rastegar D. Treatment of opioid use disorder in primary care. BMJ. 2021;373:n784. Published 2021 May 19. doi:10.1136/bmj.n784
- Becker SJ, Scott K, Helseth SA, et al. Effectiveness of medication for opioid use disorders in transition-age youth: A systematic review. J Subst Abuse Treat. 2022;132:108494. doi:10.1016/j.jsat.2021.108494
- Brogdon H, Facer KL, Cox EJ, Carlson RH Jr, Wurzel JF 3rd. Rapid Transition to Buprenorphine in a Patient With Methadone-Related QTc Interval Prolongation. J Addict Med. 2022;16(4):488-491. doi:10.1097/ADM.0000000000000935
- Wood CA, Duello A, Miles J, et al. Acceptance of medications for opioid use disorder in recovery housing programs in Missouri. J Subst Abuse Treat. 2022;138:108747. doi:10.1016/j.jsat.2022.108747
- Greiner MG, Shulman M, Opara O, et al. Surmounting Withdrawal to Initiate Fast Treatment with Naltrexone (SWIFT): A stepped wedge hybrid type 1 effectiveness-implementation study. Contemp Clin Trials. 2023;128:107148. doi:10.1016/j.cct.2023.107148