Agonist, Partial Agonist, and Antagonist Treatment
The different medications for OUD are based on their activity on the mu opioid receptor in the brain. Opioid agonists, such as methadone, bind to and fully activate the receptor; partial agonists, such as buprenorphine, bind to and partially activate the receptor; and antagonists, such as naltrexone, bind to the receptor but do not activate it, and they block other opioids from binding to and activating the receptor. All are effective treatment for OUD.
Agonists act on the opioid receptor to alleviate withdrawal and cravings, but when used properly, they do not provide the same euphoria, or “high,” of a misused opioid. Methadone has the longest medical history of effectiveness in reducing opioid use and overdose and is dispensed only in federally licensed OTPs that typically dispense and administer medication daily.
- Methadone is a treatment option recommended for participants with OUD who may benefit from daily dosing and supervision to increase adherence and/ or for those for whom buprenorphine or extended-release naltrexone has been unsuccessful.
- The administration of methadone is monitored until the participant's clinical response and behavior demonstrate that the prescribing of nonmonitored doses is appropriate.
- Abrupt discontinuation of methadone causes acute withdrawal. Participants should be warned about this and encouraged not to miss appointments or medication doses.
- Participants who discontinue treatment with methadone and then resume opioid use should be made aware of the risks associated with opioid overdose, especially increased risk of death.
- The titration of methadone to an effective dose to reduce cravings is a slow process, and during this time opioid use is not uncommon in patients. An effective dose is reached when opioid craving and use have diminished while observing for opioid side effects such as sedation.
Partial agonists, as the name implies, produce effects similar to those of full agonists but have fewer opioid-related side effects. Buprenorphine is the most effective partial agonist medication to reduce opioid craving and use and can be prescribed in any clinic where either a doctor (MD or DO) or advanced practice provider (physician assistant or nurse practitioner) has received extra training and an X-waiver on their Drug Enforcement Agency (DEA) license.
Buprenorphine (Partial Agonist)
- Buprenorphine may be started in a medical office, hospital, or jail/prison or at home.
- While all treatment court participants will participate in psychosocial treatment, such treatment is not necessary before beginning buprenorphine treatment, per the 2020 ASAM guidelines for the treatment of OUD and SAMHSA TIP 63, Medications for Opioid Use Disorder.
- Some participants who are stable after long-term treatment may decide to try tapering off the medication. Buprenorphine taper and discontinuation is a slow process (over several months), and close monitoring by the prescribing clinician is recommended.
- Abrupt discontinuation of buprenorphine precipitates acute withdrawal and increases the risk of opioid overdose. Participants should be warned about this and encouraged not to miss appointments.
Antagonists work by blocking the action of opioid receptors. If a participant is treated with an antagonist medication and then starts to use opioids, the antagonist will block the opioid receptors and the patient will not feel any effects from the opioid. Additionally, if an opioid antagonist is given to someone with active opioid use, precipitated withdrawal will occur.
Extended-Release Naltrexone (Antagonist)
- Naltrexone is a treatment option for preventing recurrence for those in remission from moderate to severe OUD, particularly among highly motivated participants likely to continue to adhere to treatment following the completion of criminal justice monitoring.
- To start naltrexone, a person must be abstinent from opioids for at least 7 to 10 days.
- Oral naltrexone (Revia) has not been found to be effective for treatment of OUD; however, the injectable monthly formulation, extended-release naltrexone, has been found to be effective for treatment of moderate to severe OUD.
- Extended-release injectable naltrexone
is a monthly injection shown to be more
effective than psychosocial treatment
alone at reducing recurrence risk and
equally effective as sublingual buprenorphine
in large randomized controlled
trials. Naltrexone has no risk for diversion
or overdose. However, individuals
who stop taking naltrexone and experience
a recurrence are at increased risk
Patients maintained on naltrexone will have diminished tolerance to opioids and may be unaware of the consequent increased sensitivity to opioids if they stop taking naltrexone. Patients who discontinue antagonist therapy should be made aware of this phenomenon. If the patient stops naltrexone and resumes use of opioids in doses that do not reflect the degree to which they have lost tolerance, there is risk of an opioid overdose. (The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder, 2020 Focused Update, page 45.)
- There is no recommended length of treatment with extended-release injectable naltrexone. Duration depends on clinical judgment and the participant's individual circumstances. Because there is no physical dependence associated with naltrexone, it can be stopped abruptly without withdrawal symptoms, although as discussed above, there is an increased risk of overdose with recurrence due to decreased tolerance to opioids during the period of abstinence.
- As with opioid agonists and partial agonists, participants who discontinue antagonist therapy and resume opioid use should be made aware of the increased risks associated with an opioid overdose, and especially the increased risk of death due to loss of opioid tolerance and hypersensitivity to opioids.