Use and misuse of opioid agonists in opioid addiction
ABSTRACT
Although methadone (an opioid agonist) and buprenorphine (a partial opioid agonist) have evidence to support their use in treating opioid use disorder, they remain misunderstood and underutilized. In this article, we outline the risks and benefits of using these drugs as maintenance therapy in opioid-dependent patients.
KEY POINTS
- Opioid use disorder is potentially lethal and has become more prevalent in the United States over the past few decades.
- The opioid agonist methadone and the partial agonist buprenorphine are the currently recommended treatments for patients who need opioid maintenance therapy. However, they carry the risk of adverse effects (eg, respiratory depression, QTc interval prolongation, hepatotoxicity), diversion, and overdose.
- Patients being considered for opioid agonist therapy need a comprehensive assessment including a thorough medical history and physical examination, psychiatric evaluation, psychosocial appraisal, and determination of readiness to change.
- When methadone and buprenorphine are properly prescribed they confer significant benefits, including reduction or elimination of opioid use, reductions in overdose risk, and positive changes in behavior and lifestyle.
NALTREXONE IS LESS EFFECTIVE THAN METHADONE, BUPRENORPHINE
Besides methadone and buprenorphine, the only other approved option for treating opioid use disorder is the opioid antagonist naltrexone.
Naltrexone has significantly less abuse potential, as it provides no euphoria, but patients do not like it. Even with the long-acting formulation (Vivitrol), naltrexone treatment is significantly less effective than methadone or buprenorphine.23–25 Further, although naltrexone is not a controlled substance and so does not face the same scrutiny as the agonist therapies, there are other significant barriers. Additional information on naltrexone is presented in reviews by Modesto-Lowe and Van Kirk24 and Woody.25
OBSTACLES TO TREATMENT
People hold conflicting views about opioid agonist therapy. Some believe that “trading one drug for another” is not a legitimate therapeutic strategy, and they may feel ashamed of being on maintenance therapy.26 Similarly, some argue that the answer to establishing stable abstinence does not lie simply in prescribing medications.
,The contrary argument is that these medications, if used appropriately, confer many benefits such as reducing the medical and psychosocial sequelae of opioid addiction.18 In fact, properly treated patients no longer meet the diagnostic criteria of opioid use disorder, and both methadone and buprenorphine are on the World Health Organization’s (WHO) list of essential medicines.27
Despite endorsement by the WHO, the stigma attached to the opioid agonists has been difficult to overcome. Patients with opioid use disorder may be viewed with distrust by healthcare providers and often do not feel welcome in healthcare settings or in self-help recovery groups.28
Barriers to methadone therapy
Federal regulations on methadone prescribing and use were established to promote patient safety and decrease diversion, but they may also complicate access to care.29 They stipulate that to qualify for methadone maintenance, patients need to demonstrate opioid addiction for 1 year, except for pregnant women and those who have been incarcerated in the past 6 months. Patients under the age of 18 must have 2 documented failed treatment episodes as well as approval by a guardian to receive treatment.
Inconvenience. Methadone can be prescribed for opioid dependence only by an accredited treatment program. Patients must therefore travel to the clinic and wait to be evaluated on a daily basis for a minimum of 90 days. Only after they demonstrate consistent responsible behavior and negative results on urine testing do they become eligible to take methadone home.29 If a patient is to travel out of the area during the initial 90 days of treatment, he or she must make arrangements in advance to find a clinic that will provide a “guest dose.”
The inconvenience arising from the regulations may deter some patients from seeking methadone therapy. In spite of this, once patients are started on methadone, more of them continue treatment than with buprenorphine.18 A proposed reason is that methadone is a potent full opioid agonist and therefore relieves withdrawal symptoms and craving more effectively than buprenorphine, which is a partial agonist.30 Another possible reason is the higher level of supervision afforded by methadone clinics, which require daily contact for at least 90 days.
Safety concerns arise from methadone diversion, as illicit use may have lethal consequences. In the past decade, deaths from methadone overdose have risen significantly, most of them due to respiratory depression or torsade de pointes.13 However, most cases of diversion and overdose involve methadone that is prescribed for pain by individual practitioners and not from maintenance programs.13
Advantages of buprenorphine
Together, methadone’s lethality, stigma, and inconvenience may contribute to patients preferring buprenorphine.31
The regulations governing buprenorphine’s use are less restrictive than those with methadone. For example, patients must have a diagnosis of opioid addiction to be prescribed buprenorphine, but they are not required to carry the diagnosis for a year before treatment.31 Additionally, they do not need to travel to a federally approved opioid treatment center daily and can receive buprenorphine directly from a physician in an outpatient setting.
Under the Drug Abuse Treatment Act (DATA) of 2000, any physician can apply for a waiver to prescribe and dispense buprenorphine in his or her office. To qualify for an initial waiver, physicians must either obtain certification in the fields of addiction medicine or addiction psychiatry or complete an approved 8-hour training session.32 Each physician starts with a maximum of 30 patients, but can apply to treat up to 100 patients after 1 year and eventually up to 275 patients. Physicians must document every buprenorphine prescription they write and be able to refer patients for counseling.31
As of February 2017, nurse practitioners and physician assistants can also apply for a DATA 2000 waiver. All waivered providers are subject to unannounced visits from the Drug Enforcement Administration once every 5 years.32
While there are no federal restrictions on the amount of buprenorphine that can be dispensed, some states and some insurance companies have placed restrictions on dose or length of treatment.33 Buprenorphine patients can fill their prescriptions at any pharmacy and are permitted to bring their medication home, which improves access to care. However, office-based outpatient treatment is not without risk, and preventing buprenorphine diversion remains a challenge.34
‘Lending’ buprenorphine is a felony
Addicts have illegally used buprenorphine to self-treat opioid withdrawal, craving, and dependence.35 Its misuse has also been coupled with self-treatment of conditions that include depression and pain.36
A survey found that 83.7% of patients deem buprenorphine diversion to be appropriate; further, most patients said they consider it unethical to withhold prescribed buprenorphine from individuals showing symptoms of withdrawal.34 Physicians who prescribe buprenorphine must inform their patients that even “lending” or giving away their medication is a felony.
Prescribing physicians must also be diligent about monitoring for signs of diversion such as inconsistent urine toxicology screens, “lost” medication, and requests for early refills or escalating doses.37
