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At present, there are no direct interventions that are capable of reversing the effects of drugs of dependence on learning and motivation systems. Instead, the management of opioid dependence often consists of pharmacotherapy with metha- done and buprenorphine, which do not eliminate physical dependence on opioids. These medications instead reduce the use of illicit opioids and produce very strong positive health outcomes as measured by decreased mortality, improved men- tal and physical health, and reduced risk of disease transmis- sion. Considering the high rate of relapse after detoxification, medication-assisted treatment with methadone or buprenor- phine is currently considered to be the first-line treatment for patients with opioid use disorder. However, outpatient medication-assisted treatment is not a viable option for patients who are pregnant, with comorbid benzodiazepine or alcohol dependence (risk of overdose), with severe unstable psychiatric conditions, and/or with acute or severe liver disease [84; 85]. Effective use of medication-assisted treatment in the outpatient setting requires access to the agonist and a support system to reinforce accountability. Prior to initiating agonist mainte- nance therapy, the patient and all members of the interpro- fessional care team should be aware of the treatment goals, expectations and responsibilities, and potential risks [85]. The Substance Abuse and Mental Health Services Administration has identified best practices when prescribing medication for the treatment of opioid use disorder [86]: • Assess the need for treatment • Educate the patient about how the medication works and the associated risks and benefits; obtain informed consent; and educate on overdose prevention • Evaluate the need for medically managed withdrawal from opioid • Address co-occurring disorders • Integrate pharmacologic and non-pharmacologic therapies • Refer patients for higher levels of care, if necessary Any treatment for opioid dependence must take into consid- eration the chronic relapsing nature of opioid dependence, characterized by a variable course of relapse and remission in many patients. Treatments should emphasize patient moti- vation, psychoeducation, continuity of care, integration of pharmacotherapy and psychosocial support, and improved liaison between the treatment staff and the judicial system. Pharmacotherapy should be offered in a comprehensive health- care context that also addresses the psychosocial aspects of dependence [70; 86; 84]. Due to the chronic nature of opioid use disorder, the need for continuing medication-assisted therapy should be re-evaluated periodically. There is no maxi- mum recommended duration of maintenance treatment, and for some patients, treatment may continue indefinitely. Patients with opioid use disorder frequently suffer from physical and psychiatric disorders, and targeted interventions of psychiatric
comorbidity are essential in improving treatment outcome for these patients. Polysubstance abuse is the rule rather than the exception in opioid dependence, and concurrent use of other substances should be carefully monitored and treated when necessary. Incarceration should never automatically result in discontinuation of an existing treatment; imprisonment offers a window of opportunity to initiate or restart treatment with a necessary continuation after release [70; 86; 84]. Agonist Replacement Therapy The goal of opioid replacement therapy is to reduce illicit drug use and associated health risks, with secondary goals of reducing unsafe sexual practices, improving vocational and psychosocial functioning, and enhancing quality of life. The theoretical basis of opioid replacement stems from the finding that chronic opioid use results in an endogenous opioid defi- ciency as a result of the down-regulation of opioid production. This creates overwhelming cravings and necessitates interven- tions that shift the dependent patient’s attention and drive from obsessive preoccupation with the next use of opioids to more adaptive areas of focus, such as work, relationships, and non-drug leisure activities [87; 88]. The neurobiologic changes resulting from prolonged opioid exposure provide a rationale for specific pharmacotherapies, such as long-acting opioid agonists, that are aimed at stabilizing these complex systems [88; 89]. Opioid agonist maintenance treatment stabilizes brain neurochemistry by replacing short- acting opioids, which can create rapid changes in opioid levels in the serum and brain, with a long-acting opioid that has relative steady-state pharmacokinetics. Opioid agonist maintenance treatment is designed to have minimal euphoric effect, block the euphoria associated with administration of exogenous opioids (competitive antagonism), eliminate the risk of infectious disease and health consequences associated with injection drug use, and prevent opioid withdrawal [88; 89]. Successful maintenance treatment entails stabilization of opi- oid dependence through opioid receptor occupation. Positron emission tomography studies have revealed that only 25% to 35% of brain opioid receptors are occupied during steady-state methadone maintenance, suggesting that unoccupied opioid receptors disrupted during cycles of opioid abuse could nor- malize during methadone maintenance [87; 89]. Additionally, opioid replacement therapy blocks much of the euphoria from illicit heroin use. Long-term opioid agonist treatment also has a positive impact on public health, through significantly reducing overdose deaths, criminal activity, and the spread of infectious disease [87; 89]. As of 2020, 509,008 patients in the United States were enrolled in opioid replacement therapy in 1,754 opioid treatment pro- grams [90]. However, this represents only an estimated 18% of all opioid-dependent patients. Although some have criticized the practice of methadone and buprenorphine therapy on the grounds that one opioid is merely being substituted for
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