Similar to other opioids, methadone can cause constipation, excess sweating, drowsiness, and erectile dysfunction.Patients experiencing significant oversedation should have their dose reduced as this is a sign that their dosage may be too high. 187,189 Methadone is metabolized by CYP2B6, CYP3A4, CYP2C19, CYP2D6 and CYP1A2. Therefore, clinicians must consider drug interactions when administering methadone. Strong CYP3A4 inhibitors, such as clarithromycin, ketoconazole and grapefruit juice, can increase effects of methadone and make a patient more susceptible to arrhythmias. Strong CYP3A4 inducers, such as rifampin and phenytoin, can decrease methadone levels and cause relapse or withdrawal. 190 The optimal length of methadone treatment has not yet been determined, and guidelines recommend individualized treatment plans. Most patients will require chronic, possibly even lifetime treatment, to prevent relapse. Methadone treatment should also be used in conjunction with psychosocial treatment. 187,190 Clonidine Clonidine is an alpha-2 adrenergic agonist. Its central effect on reducing noradrenaline levels helps to reduce many symptoms of opioid withdrawal, including sweating, anxiety, intestinal cramps, diarrhea, nausea, and irritability. Clonidine is often used as an adjunctive treatment. It is frequently combined with non-narcotic medications targeting opioid withdrawal symptoms, such as non-steroidal anti-inflammatory agents (NSAIDs) for pain and ondansetron for nausea. It is also used in conjunction with buprenorphine and methadone, to treat withdrawal symptoms when tapering off of these medications. Clonidine has been shown to be more effective than a placebo but less effective than methadone or buprenorphine in decreasing the symptoms of severe withdrawal and improving treatment program retention and completion rates. 187 Clonidine is typically given in doses of 0.1-0.3 mg every 6 to 8 hours, with a maximum recommended daily dose of 1.2mg. It is typically avoided in patients with blood pressure below 90/60mmHg, heart rate less than 60, or in patients with orthostatic hypotension. Clonidine is contraindicated in people with hypotension, pregnancy, moderate to severe kidney disease, cardiac instability, and psychosis. Adverse effects include low blood pressure and sedation, which can limit the use of clonidine. 187 Medication Assisted Treatment (MAT) Once withdrawal has completed, careful transition to a treatment program is recommended. Most patients with moderate to severe opioid use disorder benefit from a combination of medication and psychosocial treatment, also known as medication assisted treatment (MAT). Psychosocial treatment alone can be considered for patients who are highly motivated, have strong psychosocial supports and those with mild opioid use disorder. However, most research shows the superior efficacy of MAT with reduced substance use and higher abstinence rates when compared with psychosocial treatment alone. 191,192,193
The end goal of medication assisted treatment is sustained, long term remission of substance use disorder. MAT has been shown to increase treatment retention, improve survival, decrease illicit opioid use and criminal activity, improve birth outcomes in pregnant women with substance use disorders, decrease the risk of bloodborne illness, and increase the ability to earn and retain employment. An integrated approach to care is recommended, with treatment intensity continuously adapting over time to the patient’s changing needs. 191,194 Adjunctive psychosocial treatment is recommended for patients with opioid use disorder. Individual or group counseling can help patients work through their treatment with licensed counselors and others who are having similar experiences. Mutual help groups are also recommended, such as Narcotics Anonymous. Selection of a mutual help group should be made carefully to ensure it is a good fit for the patient and their psychosocial needs. 192 Buprenorphine Buprenorphine is strongly recommended as the first line treatment MAT in patients with moderate to severe opioid use disorder. Its partial action at the opioid receptor allows for easier stabilization at the beginning of therapy while minimizing the risk of overdose. Since it does have some action at the opioid receptor, it can cause withdrawal symptoms when it is discontinued, so tapering is recommended. In addition, diversion of buprenorphine has been reported, so prescribers should utilize this medication with care and consider its use carefully in patients with a history of diversion. 187,194 Naltrexone Naltrexone, an opioid receptor blocker, is recommended to prevent relapse in patients who are no longer dependent on opioids. By blocking the opioid receptor, patients who relapse and use opioids while taking naltrexone experience no euphoria or effect of the opioid. Naltrexone also does not create any physiologic dependence or withdrawal symptoms when discontinued. However, it causes immediate opioid withdrawal symptoms when taken by patients who are physically dependent on opioids, so it requires the patient to be completely withdrawn from opioids before it can be initiated. This includes methadone and buprenorphine being used to treat opioid use disorder. Complete withdrawal can be difficult to achieve in patients with severe opioid use disorder, limiting the use of naltrexone. 187,194 Naltrexone is a non-controlled medication available in oral tablets taken daily and an intramuscular formulation administered every four weeks. Poor medication adherence is a significant issue with naltrexone that often limits its use; using the injectable extended-release formulation overcomes some of these limits, but studies show adherence to this formulation is lower than buprenorphine. If naltrexone therapy is chosen, it is preferable to start intramuscular naltrexone; when compared to placebo or no medication treatment, oral naltrexone was not found to be more effective reducing illicit opioid use or treatment retention.
Book Code: CA23CME
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