Treatment of Opioid Use Disorder Treatment for opioid use disorder is evolving. Previously, treatment involved stopping opioids, managing withdrawal, and then focusing on avoiding relapse using psychosocial therapy. Psychosocial therapy was thought to help patients develop healthy habits for non-drug lifestyles. Medications were only prescribed for short-term use to ease the transition and were then discontinued. However, research has shown that short-term medication treatment is not effective; many patients will require long-term therapy. 185 Treatment of opioid use disorder may be best conducted by specialists in addiction medicine due to the complexity of this condition. Treatment often starts with the treatment of opioid withdrawal. Patients who are physiologically dependent on opioids can experience opioid withdrawal syndrome after abruptly discontinuing or reducing the dose of opioids used. Symptoms of opioid withdrawal syndrome include tachycardia, hypertension, piloerection, mydriasis, rhinorrhea, lacrimation, insomnia, and gastrointestinal distress. This clinical syndrome is informally considered to be non- life threatening; however, opioid withdrawal can cause severe fluid loss and resultant electrolyte abnormalities that can lead to hemodynamic instability and death. 186 The clinical time course of opioid withdrawal syndrome is typically dependent on the half-life of the opioid used. Opioids with a short half-life have a more rapid onset of withdrawal symptoms; for example, heroin has a half-life of 3 to 5 hours, and is associated with an onset of withdrawal within 12 hours of the last use. Opioids with a longer half- life, such as methadone with a half-life of up to 96 hours, can lead to withdrawal symptoms 1 to 3 days after the last use. The duration of withdrawal is also dependent on the half-life of the opioid used; heroin withdrawal typically lasts 4 to 5 days, and methadone withdrawal can last 7 to 14 days or longer. 186 Medically Supervised Withdrawal Medically supervised or detoxification, can be used on an inpatient or outpatient basis to help reduce withdrawal symptoms and safely transition the patient to a medication-assisted treatment program. This typically involves patients visiting a treatment center on an inpatient or outpatient basis for counseling, medications, and medical treatment. Medically supervised withdrawal should be incorporated as part of a comprehensive treatment program, and should not be used as a standalone treatment. People who complete detoxification and do not move on to further treatment are at a high risk of relapse, and after completing withdrawal from opioids, they often experience a lower physiological tolerance to opioids. This creates a high risk of overdose if the patient returns to using the same dosages of opioids that they were using prior to medically supervised withdrawal. 186 withdrawal,
Medications used in the treatment of opioid withdrawal syndrome focus on targeting the underlying pathophysiology of the condition. The euphoria produced by opioids is primarily a result of the opioid binding to the μ-opioid receptor. This binding results in a suppression of the release of norepinephrine in the locus coeruleus, causing the characteristic symptoms of sedation, decreased respiration rate, and hypotension associated with opioid intoxication. When opioids are discontinued or abruptly tapered, an increase of norepinephrine release from the locus coeruleus leads to the characteristic withdrawal symptoms of diaphoresis, lacrimation, mydriasis and tachycardia. Treatment of withdrawal focuses on these mechanisms, with μ-opioid receptor agonists and partial agonists, as well as α 2 agonists, being critical elements of opioid withdrawal therapy. 186 Buprenorphine Buprenorphine is a partial agonist with a high affinity for the μ-opioid receptor that is used alone or in combination with naloxone for the treatment of both opioid withdrawal and opioid use disorder. Since buprenorphine partially activates the opioid receptor, it provides effective treatment for opioid withdrawal symptoms. Naloxone, an opioid antagonist, has little effect when taken orally but is often included in combination products with buprenorphine to prevent intravenous abuse of buprenorphine – if buprenorphine/naloxone is liquefied and injected, naloxone will take effect and prevent buprenorphine from activating the μ-opioid receptor. This effect is generally avoided when buprenorphine/naloxone is taken as prescribed, though a small amount of naloxone can be absorbed sublingually and displace other opioids from the opioid receptor, resulting in precipitated withdrawal in patients who have not had a sufficient amount of time pass since their last opioid dose. Patients taking methadone or other long-acting opioids may be at a higher risk of developing precipitated withdrawal. The use of buprenorphine monotherapy may be considered initially in patients taking long-acting opioids to minimize this effect, though buprenorphine monotherapy can also precipitate withdrawal due to its high affinity for the opioid receptor. 187 Buprenorphine has a higher affinity for the μ-opioid receptor when compared to most full opioid agonists. Because of this, buprenorphine is able to displace full opioid agonists from the receptor, precipitating withdrawal on its own if insufficient time has passed since the patient’s last dose of opioids. Patients with current opioid dependence should wait until mild to moderate opioid withdrawal sets in before initiating buprenorphine treatment in order to reduce the risk of precipitated withdrawal. In general, buprenorphine treatment should start at least 6 to 12 hours after the last heroin dose or 24 to 72 hours after the last dose of long-acting opioids. 187
Initiating buprenorphine at a lower dose can reduce the risk of precipitated withdrawal. An initial dose of 2 to 4mg is recommended, followed by observation for signs of precipitated withdrawal. If withdrawal symptoms are not experienced within 60 to 90 minutes, additional doses can be given in increments of 2 to 8mg as needed. 187 Buprenorphine has a lower risk of overdose when compared with full agonist opioids; respiratory depression is limited with a ceiling effect at higher doses. Caution is still advised, particularly when combining buprenorphine with alcohol, hypnotics, or anxiolytics, as respiratory depressive effects can be enhanced by these substances. Caution is also advised when using in patients with hepatic impairment. Buprenorphine is generally well- tolerated, but headache, anxiety, constipation, fluid retention and sleep disturbances have been reported. 187 Unlike methadone, buprenorphine can be prescribed on an outpatient basis, with some restrictions outlined in the Drug Addiction Treatment Act of 2000 (DATA 2000). Through this act, providers can apply for waivers to prescribe certain controlled substances, such as buprenorphine, from their office settings rather than from opioid treatment programs, in order to expand access to medications to treat substance use disorders. A clinician must obtain a DATA 2000 waiver, which allows trained physicians to prescribe CIII-V medications to treat opioid use disorder in an office or clinic. The physician must have a valid medical license, a DEA number, and one additional criteria such as addiction certification, board certification in addiction medicine, or other additional training. Both buprenorphine and buprenorphine/naloxone may be prescribed with a DATA 2000 waiver. However, the DATA 2000 act limits the number of patients who can be treated at one time. The 2018 Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act expanded DATA 2000 to include nurse practitioners and physician assistants to increase access to treatment. More information on training and registration is available at buprenorphine.samhsa.gov. 187 Prescribers will receive a DATA 2000 waiver identification number that begins with X. Both their DEA number and DATA 2000 waiver number must be provided on prescriptions. The “Buprenorphine Pharmacy Lookup” tool on the SAMHSA website can be used to verify a physician’s DATA waiver and the number of patients they may treat at one time. 188 Since buprenorphine can be prescribed on an outpatient basis, some additional steps are recommended to decrease diversion. The American Society of Addiction Medicine recommends frequent office visits to obtain refills, observed dosing, and pill counts, as well as urine drug screens and frequent access to state prescription drug monitoring programs. Like methadone, buprenorphine should be used in conjunction with psychosocial treatment. There are no well-established recommendations for length of therapy. 187
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