Any patient diagnosed with a moderate or severe opioid use disorder should be assessed for medication assisted treatment, the use of medications as part of a comprehensive treatment paradigm [29, 47]. Opioid agonists used in medication assisted treatment for opioid dependence, such as methadone and buprenorphine, can be used without prior detoxification. Extended-release injectable naltrexone is approved for relapse prevention and can be administered 7 to 10 days after last opioid use.
Methadone, an opioid agonist, is a safe and effective pharmacologic therapy for the treatment of opioid use disorders [47, 48]. Recently, with the explosion of prescription opioid abuse and dependence in the United States, methadone treatment has been used successfully by opioid treatment programs (OTPs) for the treatment of prescription opioid abuse . Methadone is a synthetic mu opioid receptor agonist with pharmacological properties qualitatively similar to morphine and was originally used to treat the painful symptoms of withdrawal from heroin and other opioids [50, 51]. Administered daily as an oral dose for the treatment of opioid dependence, an individualized therapeutic dosage of methadone is determined to maintain an asymptomatic state and stabilize a patient, without episodes of opioid overmedication or withdrawal. Minimum retention time in treatment varies for residential and outpatient methadone treatment programs. The National Institutes of Health consensus panel  concluded that individuals treated for fewer than three months with methadone do not show substantial medical gain. Methadone is usually the least expensive medication and when used in evidence-based treatment paradigms is cost effective and can result in reduced drug use, improved health outcomes, as well as improvements in quality of life [47, 53, 54]. Relapse to opioid misuse and abuse is common when methadone is discontinued without further support or behavioral treatment.
In the United States, methadone for the treatment of opioid dependence can only be dispensed in specialty clinics called Opioid Treatment Programs (OTPs). Studies have also shown that individuals receiving medication assisted treatment with methadone are at a reduced risk of death, half as likely to become infected with HIV, better able to comply with other medical therapies, less involved in crime, have an enhanced quality of life, with positive cognitive, emotional, and social functioning [55–58]. The federal regulations pertaining to the use of methadone for opioid use disorders do not preclude the integration of primary care into the specialty clinic . Numerous models of integrated care and treatment have been piloted including studies showing the efficacy of transferring stable patients receiving mediation assisted treatment with methadone to primary care providers to continue treatment [60–62]. In such an arrangement where comprehensive medical care is provided with methadone maintenance treatment, it has been shown that ambulatory care increases with emergency room visits decreasing, resulting in cost-effective care .
Buprenorphine is a partial opioid agonist with a very high affinity for the mu opioid receptor . Because it is a partial agonist, the effect of buprenorphine cannot be increased by taking larger amounts. This makes the drug less reinforcing, giving it less value as a drug of abuse and a favorable safety profile. The high receptor affinity creates a blockade effect so that, when dosed properly, the euphoric effects of other opioids are blunted or blocked. However, the abuse of other substances, such as benzodiazepines, may enhance respiratory depression and remains a contraindication with the use of opioid agonists. The combination of the partial agonist and high receptor affinity gives buprenorphine another unique property. It will cause an acute precipitated withdrawal if ingested in the presence of most full-agonist opioids. This also serves to reduce the abuse potential of buprenorphine. As an additional deterrent, buprenorphine has been formulated to include naloxone. Buprenorphine has poor oral bioavailability and moderate sublingual bioavailability. Therefore, formulations for opioid addiction treatment are in the form of sublingual tablets . Naloxone, however, is not. The patient who takes buprenorphine combined with naloxone as directed will experience only the buprenorphine. However, if injected, the naloxone is fully effective and immediate withdrawal is experienced. Depot and implantable formulations are in development.
Buprenorphine has been shown to be safe and effective in the treatment of both injection (heroin) opioid use and prescription drug abuse and dependence [66, 67]. A recent study has shown that in a primary care setting using buprenorphine, prescription opioid-dependent patients showed better clinical outcomes compared to patients who were dependent on heroin . Also, retention in buprenorphine maintenance treatment has been shown to reduce emergency department use, thus lowering the overall cost of care .
Buprenorphine can be prescribed, within certain parameters, by physicians in any medical practice. To do so, a physician must hold a current state medical license, a valid DEA registration number, and meet one or more of the following training requirements: hold a subspecialty board certification in addiction psychiatry from the American Board of Medical Specialties, hold a subspecialty board certification in Addiction Medicine from the American Osteopathic Association, hold an addiction certification from the American Society of Addiction Medicine, or have completed not less than 8 hours of authorized training on the treatment or management of opioid-dependent patients. This training may include classroom situations, seminars at professional society meetings, electronic communications, or other media. An office-based setting provides increased access to medication assisted treatment for opioid dependence in a less stigmatized environment and enables integrated primary medical care with the treatment of substance use disorders . Medication assisted treatment with buprenorphine is reviewed in SAMHSA Treatment Improvement Protocol 40 .
Naltrexone is a long-acting, opioid antagonist that blocks the euphoric effects of opioids binding the mu opioid receptor . Unlike opioid agonists, administration does not relieve withdrawal nor does it cause withdrawal upon discontinuation. Due to naltrexone’s opioid antagonism, patients prescribed naltrexone for opioid dependence must abstain from opioids for a minimum of seven days prior to starting naltrexone treatment to avoid the precipitation of opioid withdrawal. Naltrexone is most effective when utilized subsequent to the medical detoxification from opioids. The effectiveness of naltrexone treatment depends upon patient motivation and a social support system that promotes medication adherence . Because of the need for adherence support interventions, the most recent Cochrane review of oral naltrexone treatment for relapse prevention to opioid use commented that oral naltrexone has not been scientifically demonstrated to be superior to other forms of treatment for opioid dependence . Extended-release injectable naltrexone (Vivitrol) addresses the generally poor compliance with oral naltrexone through a monthly injectable formulation. Increased medication adherence was shown in a recent Phase 3 clinical trial that confirmed safety and efficacy of extended-release injectable naltrexone in the prevention of relapse to heroin use in a cohort of injection drug users . A higher retention in care and higher rates of opioid-free urine screens were observed along with a significant reduction in opioid craving compared to placebo. Currently, studies are underway to determine the most efficacious primary care model(s) for the use of extended-release injectable naltrexone in the treatment of relapse prevention to heroin use.