What clinicians need to know about treating opioid use disorder
Choose medication and non-medication options to fight abuse and relapse
Methadone during pregnancy. Methadone is the treatment of choice for opioid-dependent women during pregnancy33 and is listed as pregnancy category C because it can result in physiologic dependence of the newborn, although there are no documented controlled studies in humans to assess this risk. Methadone can be used while breast-feeding as long as patients are HIV-negative and not abusing other drugs.34,35 Because the methadone concentration in breast milk generally is low, the medication can be administered to nursing mothers after a careful consideration of risks and benefits.
Methadone administration. There are stringent eligibility criteria for methadone administration; not all physicians are authorized to prescribe methadone. Its use is federally regulated and only licensed treatment programs and licensed inpatient detoxification units can prescribe and dispense methadone in controlled settings and under the direct supervision of clinical personnel (Table 5).36 Patients meeting eligibility criteria can attend a specialized methadone clinic.
One of the challenges when using methadone for long-term management of OUD is tapering the dosage and attempting to discontinue the medication. Discontinuation of methadone leads to withdrawal symptoms and requires a carefully tailored tapering schedule. The literature on methadone tapering is limited. Tapering schedules could differ from practice to practice and, in many cases, are highly individualized based on the need and response of specific patients.
Dosage reduction schedules can last from 2 to 3 weeks to 6 months. Studies indicate rapid reduction worsens treatment outcomes and protracted tapering is associated with better outcomes. A suggested tapering schedule could involve decreasing the dosage by 20% to 25% until reaching a dosage of 30 mg/d, then decreasing by 5 mg/d every 3 to 5 days until reaching a dosage of 10 mg/d, before finally decreasing by 2.5 mg/d every 3 to 5 days.
Some randomized trials have shown better outcomes with long-term treatment. The goal of many programs is transitioning from maintenance treatment to abstinence. However, programs targeting maintenance rather than abstinence have been shown to be more effective.
The FDA has no defined limits for treatment duration with either methadone or buprenorphine. Therefore, the decision to taper or discontinue either medication should be made carefully case by case, using sound clinical judgment. Studies show that methadone treatment could reduce the spread of HIV,37,38 decrease criminal behaviors,39 and reduce overall mortality rates.40 A follow-up study comparing individuals randomly assigned to receive methadone or buprenorphine for OUD showed reduced risk of mortality overall40 in both groups.
Adverse events reported during treatment with methadone include decreased libido, erectile dysfunction, constipation, drowsiness, QTc prolongation, and torsade de pointes.41 Therefore, the FDA recommends obtaining a detailed medical history and baseline electrocardiogram (ECG), with a repeat ECG within the first month of treatment and then annually. Informing patients about the possibility of arrhythmias is part of the informed consent process before starting methadone.
Clinicians also should be vigilant when using methadone in combination with other medications that can prolong the QTc interval (eg, some antipsychotics). Methadone has a greater risk of fatal overdose then buprenorphine. A large-scale study of >16,000 patients reported a 4-fold increase in mortality resulting from methadone overdose compared with buprenorphine.42
BuprenorphineBuprenorphine is a partial opioid agonist at the mu opioid receptor. A full opioid agonist binds and fully activates the opioid receptors; an antagonist blocks the same. An opioid receptor partial agonist partially activates the receptor. Therefore, an opioid system partial agonist is a functional antagonist and, at lower dosages, has weak agonist effects; at higher dosages, a partial agonist antagonizes other endogenous and exogenous opioids that compete for binding at the same receptor.43 Because of the partial agonist effect, buprenorphine could result in less physical dependence and less withdrawal symptoms.
Administration. In contrast to methadone, buprenorphine can be prescribed by physicians for long-term management of OUD in the United States. Buprenorphine is available in 2 formulations: a sublingual form for daily use and a long-acting form that causes less withdrawal symptoms and cravings. In May 2016 the FDA approved the first buprenorphine implant for use in opioid dependence.44,45
To prevent withdrawal symptoms, a 24-hour period of opioid abstinence is recommended before starting buprenorphine or buprenorphine/naloxone treatment.46 Although lacking empirical evidence, catechol-O-methyltransferase (COMT) inhibitors, such as entacapone, have an anti-craving affect and are used by some clinicians to improve adherence with buprenorphine. This is because of their ability to balance dopamine, which is central to the reward pathway responsible for cravings. Although use of COMT inhibitors might make sense intuitively, such use is off-label and should be based on clinical judgment and a review of the available literature. A study showed that tapering buprenorphine for 4 weeks in combination with naltrexone improved the abstinence rate.47
