_____________________________________________________ Responsible and Effective Opioid Prescribing
Discontinuation of opioid use must be implemented slowly and cautiously to avoid a marked abstinence syndrome. Withdrawal symptoms may not begin for days after abrupt discontinuation of methadone or buprenorphine given their longer half-lives. Protracted abstinence, or post-acute withdrawal, may last for several months and is characterized by asthenia, depression, and hypotension. Post-acute withdrawal is more likely to occur with methadone than other opioids [72]. The three primary treatment modalities used for detoxification are opioid agonists, non-opioid medications, and rapid and ultra-rapid opioid detoxification [72]. The most frequently employed method of opioid withdrawal is a slow, supervised detoxification during which an opioid agonist, usually methadone, is substituted for the abused opioid [80]. Methadone is the most frequently used opioid agonist due to the convenience of its once-a-day dosing [72]. Methadone is highly bound to plasma proteins and accumulates more readily than heroin in all body tissues. Methadone also has a longer half-life, approximately 22 hours, which makes withdrawal more difficult than from heroin. Substitution therapy with methadone has a high initial dropout rate (30% to 90%) and an early relapse rate. Alternative pharmacologic detoxification choices include clonidine (with or without methadone), midazolam, trazodone, or buprenorphine [80]. Naltrexone is used following medically supervised withdrawal to help prevent relapse to opioid misuse [81]. Many opioid withdrawal symptoms, such as restlessness, rhinorrhea, lacrimation, diaphoresis, myosis, piloerection, and cardiovascular changes, are mediated through increased sympathetic activation, the result of increased neuron activity in the locus coeruleus. Non-opioid agents (such as clonidine), which inhibit hyperactivation of noradrenergic pathways stemming from the locus coeruleus nucleus, have been used to manage acute withdrawal [80; 82]. The first non-opioid treatment approved for the management of opioid withdrawal symptoms is lofexidine [83]. In studies, lofexidine resulted in less severe withdrawal symptoms and greater treatment retention than placebo. However, some withdrawal symptoms, including anxiety and myalgias, are resistant to clonidine; benzodiazepines and nonsteroidal anti-inflammatory agents may be necessary to treat these symptoms. To mitigate withdrawal symptoms and assist in detoxification, alpha2-agonists, opioid agonist-antagonists, benzodiazepines, and antidepressants have been used [80]. Following detoxification, patients may feel exhausted and weak. Other complications, such as slight variations in hemodynamic status and gastrointestinal tract symptoms, follow quickly and may take several days to resolve. Muscle cramps and low back pain can be treated with nonsteroidal anti-inflammatory drugs. However, the newer cyclooxygenase-2 (COX-2) inhibitors may be advantageous because they produce fewer gastrointestinal side effects [80]. Insomnia is a frequent aspect of acute and protracted withdrawal, as opioids disrupt the normal sleep-wake
cycle and many addicts require narcotics to sleep. Although long-term disruption of the normal sleep-wake cycle cannot be corrected rapidly, melatonin (3 mg), benzodiazepines, or antihistamines can be used with beneficial effects. Hypnosis and relaxation techniques are nonpharmacologic methods that may also be used [80]. Psychosocial treatments offered in addition to pharmacologic detoxification treatments positively impact treatment retention and completion, results at follow-up, and compliance [84; 85]. Ultra-Rapid Opioid Detoxification Ultra-rapid opioid detoxification (UROD) has been developed as a means of avoiding the physical symptoms of withdrawal from opioids through the use of general anesthesia. UROD consists of naltrexone-assisted detoxification under heavy sedation or full anesthesia. UROD is also referred to as rapid or anesthesia-assisted detoxification. Other novel names for the process include [86]: • UROD: General anesthesia; duration <6 hours • Rapid opioid detoxification (ROD): Deep sedation; duration 6 to 72 hours • Compressed opioid detoxification (COD) and naltrexone-compressed opioid detoxification (NCOD): Duration three to six days; preceded by a period of abstinence from opioids under sedation prior to introduction of naltrexone The common underlying themes in all UROD techniques are a desire to condense the detoxification process into a shorter period to blunt the awareness of physical discomfort and to shorten the time lag between a patient’s last dose of opioid and transfer to naltrexone maintenance [86]. This is accomplished by precipitating withdrawal following the administration of opioid antagonists under deep sedation or anesthesia. Detoxification and withdrawal are rarely complete following UROD, and residual withdrawal symptoms can include drug craving, sympathetic hyperactivity, muscle pain, bone pain, nausea, vomiting, diarrhea, and insomnia. UROD does little to prevent protracted abstinence syndrome, which can last 3 to 10 weeks. Naltrexone may reduce opioid craving during the post- UROD period, with 50 mg per day recommended for relapse prevention. However, patients undergoing long-term naltrexone therapy can become sensitized to opioid drugs, heightening the risk of fatal overdose if opioid use is resumed [80]. A major shortcoming of UROD is the lack of evidence that an opioid antagonist can accelerate the restoration of neurobiologic homeostasis following opioid withdrawal [86]. Although significant drawbacks and questionable long-term efficacy exist with UROD, popular demand has proven difficult to restrain, in part due to the marketing of the procedure as a painless cure for opioid dependence. Marketing and the media have also blurred the fact that the original purpose of the procedure was to induce patients as rapidly as possible
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MDTX1625
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