(Note that use of implantable agents require stabilization on sublingual doses first.) Extended-release naltrexone
Naltrexone is not an opioid. It is a full antagonist of the mu-opioid receptor, which blocks both the euphoric and analgesic effects of all opioids, including endogenous opioids (i.e., endorphins) and also reduces cravings for opioids. 153 Naltrexone does not cause physical dependence, nor does it produce any of the rewarding effects of opioids. Patients may try to use opioids while on extended-release naltrexone, but it is unlikely that they will experience any rewarding effects from such use, unless the binding affinity of naltrexone is overcome. 147 The most common side effects of extended-release naltrexone are injection site pain, nasopharyngitis, insomnia, and toothache. Treatment initiation requires a 7-10 day period during which the patient is free from all opioids, including methadone and buprenorphine. This is usually achieved with medicallysupervised withdrawal followed by at least 4 to 7 days without any opioids (including methadone and buprenorphine). This process is a very significant barrier to naltrexone use. 147 Does MAT really work? Abundant evidence from decades of randomized trials, clinical studies, and meta-analyses suggests that agonist or partial-agonist opioid treatment used for an indefinite period of time is the safest option for treating OUD. 147, 155 (The evidence base for extended- release naltrexone is much less robust.) 147 A small randomized trial and a large cohort study demonstrated that people with OUD treated with methadone or buprenorphine are less likely to die, less likely to overdose, and more likely to remain in treatment. 153,161 MAT is also associated with lower risks for HIV and other infections, and improved social functioning and quality of life compared to people not on MAT. 30 Data suggest that MAT is more effective than psychotherapeutic interventions alone, and is just as effective whether psychotherapeutic interventions are used concurrently with medication treatment or not. Although the evidence base for intramuscular naltrexone is less robust than for methadone or buprenorphine, it has been shown to significantly decrease opioid misuse in patients with mild-to- moderate OUD. 147 For example, one trial randomized 250 patients with OUD who completed inpatient detoxification (≥ 7 days off all opioids) to 24 weeks of naltrexone intramuscular injection (380 mg/month) vs. placebo. 163 At follow-up, 90% in the naltrexone group were abstinent compared to 35% in the placebo group. Psychosocial treatments Psychosocial and/or behavioral interventions can be used in combination with medications in order to treat the “whole patient” (e.g., comorbid psychiatric symptoms, social support needs). The
Naloxone vs. Naltrexone: What’s the difference? Naloxone (Narcan) is an opioid antagonist given by injection or nasal spray to reverse overdoses. It acts within minutes and lasts for only about an hour due to rapid metabolism. Naltrexone has a very similar chemical structure to Naloxone and is also an opioid antagonist, but it acts more slowly and lasts longer. Extended-release naltrexone is used clinically to block cravings for opioids and other drugs. Naltrexone is currently available both as a once-daily oral tablet and in a once monthly, extended-release depot injection. The oral formulation, however, was found to be no better than placebo in a 2011 Cochrane review of 13 trials with 1,158 participants, 159 and only the extended-release formulation has been approved for OUD by the FDA. Patients may have an increased risk of overdose when they approach the end of the 28-day period of the extended-release formulation. 160 National Academy of Sciences, however, notes that psychosocial services may not be available to all patients and recommends that that the lack of such supports should not be a barrier to using MAT. 147 Findings related to the incremental benefit of psychosocial supports were mixed; however, the most comprehensive and current reviews were supportive of the value of psychosocial supports in addition to pharmacological treatments for OUD. Nonetheless, psychosocial, behavioral, and peer- support interventions may have many profoundly important benefits for patients beyond strictly opioid-related outcomes, such as improving self- confidence, self-advocacy, general quality of life, and improvements in legal, interpersonal, and occupational functioning. 141 Some guidelines and authors advocate for the use of psychosocial interventions, but suggest that the lack of such interventions at a given place or time should not be a barrier to the use of MAT. 147,169 Tapering protocols OUD guidelines do not recommend a duration of MAT treatment, which could be for an indefinite period of time because of the high risk of relapse with discontinuation. 147 For example, a population- based retrospective study of 14,602 patients who discontinued methadone treatment found that only 13% had successful outcomes (no treatment re-entry, death, or opioid-related hospitalization) within 18 months of taper. 169 Nonetheless, some patients may want to stop opioid agonist therapy. An ideal time frame for a trial of MAT tapering has not been established. Tapering should always be at the patient’s discretion, and all decisions should be based on a thorough dialogue
Book Code: MDAZ1124
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