Buprenorphine maintenance involves three phases: induction, stabilization, and maintenance.38 Induction takes place in a clinician's office at the time the patient experiences opioid withdrawal symptoms, typically 6 to 48 hours after taking the last opioid. Extended treatment improves clinical outcomes,23,24 and longer-term maintenance (of indefinite duration) is frequently required.
Naltrexone is a m-receptor antagonist, and therefore does not cause physical dependence or have agonist effects such as euphoria and sedation. As a result, it has no diversion value and may appeal to those who view opioid-agonist pharmacotherapy as simply trading one drug for another.39 Naltrexone is not a controlled substance and is not subject to the regulatory requirements that buprenorphine and methadone face.
Although agonists can be started in the first day or two after a patient decides to stop using opioids, patients must be opioid-free for at least seven days before starting naltrexone. That's because its antagonist properties will precipitate withdrawal if another opioid is present on the opioid receptors. During the seven-day "washout" period, opioid withdrawal symptoms can be treated with medications such as clonidine and dicyclomine, but such symptoms make patients especially vulnerable to relapse while waiting to start naltrexone.
Oral naltrexone's effectiveness as a treatment for opioid dependence has been limited by poor patient adherence. But a long-acting intramuscular form of the drug, approved by the FDA in 2010 and requiring once-a-month injection, mitigates this concern.40,41
Methadone is a full m-opioid agonist, administered daily at specialized clinics, as a maintenance therapy for opioid dependence. Although office-based physicians can prescribe methadone for pain, the drug can only be used for opioid dependence under the auspices of state- and federally regulated opioid treatment programs (http://findtreatment.samhsa.gov/TreatmentLocator/faces/quickSearch.jspx; a mobile phone application is also available at www.samhsa.gov/mobile/treat mentlocator.aspx).
Methadone, a Schedule III controlled substance with a half-life averaging 24 to 36 hours, requires daily dosing.42 Its slow metabolism and long half-life increase the risk for overdose.
Methadone is best for patients who are highly dependent on opioids and likely to benefit from a structured treatment environment with daily supervision (although patients who are doing well may earn take-home privileges so they don't have to come to the clinic every day).43 New patients should receive an initial dose of 30 mg or less, and a maximum first-day dose of 40 mg.44
Methadone use remains the standard of care for pregnant women being treated for opioid dependence, while studies of the effects of buprenorphine and naltrexone on a developing fetus continue. Although methadone's efficacy, particularly in lower doses, is similar to that of buprenorphine,45 its adverse effect profile is worse. Adverse effects include drug interactions, the potential for respiratory depression (especially in combination with alcohol or sedatives), QTc prolongation (which requires monitoring by ECG), sedation, and weight gain, and should be considered before methadone is selected as a maintenance pharmacotherapy.30,37,46 And, because relapse rates within 12 months of tapering off methadone have been reported to exceed 80%,47 both the clinician and the patient need to consider the likelihood of long-term, even lifelong, maintenance before initiating treatment.
Behavioral Interventions Are a Vital Part of the Picture
Studies evaluating the extent to which various types and amounts of counseling improve outcomes compared with pharmacotherapy alone have had conflicting results.24,48 Nonetheless, most clinicians consider counseling a critical component of treatment for opioid dependence and recommend, at a minimum, either individual or group counseling (various modalities have been shown to be effective) and regular attendance at a self-help group like Narcotics Anonymous. Contingency management, a type of therapy that uses prizes as incentives for desired behaviors; and family therapy, individual counseling, and community-based programs have all been found to improve outcomes.6,49
CASE You refer Sam to an addiction psychiatrist, who stabilizes him on 16 mg/d buprenorphine/naloxone as part of an outpatient treatment program. Sam is enrolled in a weekly buprenorphine stabilization group, where he gives a urine sample each week. He also begins seeing a social worker weekly for counseling and attends Narcotics Anonymous meetings two to three times a week. At a follow-up appointment with you six months later, he reports that he has been abstinent from oxycodone for six months, his sleep is improved, and he feels better about his chances of finding another job.
Your Role in Safeguarding the Patient
With the rising prevalence of opioid overdose, patient education aimed at crisis prevention is crucial as well. Warn patients of the risk for accidental overdose, often associated with relapse, stressing the importance of continuing treatment and taking their maintenance medication exactly as prescribed.
There are other steps that can be taken to safeguard patients—for example, providing naloxone rescue kits to patients and their families when appropriate. The clinician can also institute diversion and overdose prevention measures for patients taking buprenorphine or methadone—providing a lock box for take-home medication, implementing treatment contracts, and using a designated pharmacy to dispense buprenorphine, for example.26,27,50