Methadone treatment of OUD
Methadone is a full opioid agonist approved by the FDA for the treatment of severe pain or OUD. Methadone treatment of OUD is strictly regulated and typically is ordered and administered at an opioid treatment program that is federally licensed. Methadone for OUD treatment cannot be prescribed by a physician to a pharmacy, limiting its use in primary care practice. Methadone used to treat OUD is ordered and dispensed at opioid-treatment programs. Take-home doses of methadone may be available to patients after adherence to the regimen has been established. When used long-term, higher doses of methadone are associated with better adherence, but these higher doses can cause respiratory depression. In a study of 189 pregnant patients taking methadone to treat OUD, daily doses of 60 mg or greater were associated with better treatment retention at delivery and 60 days postpartum, as well as less use of nonprescription opioids.17 Under limited circumstances methadone can be ordered and dispensed for hospitalized patients with OUD.
Medication treatment for OUD
Methadone is a pure opioid receptor agonist. Naloxone (NAL) is an opioid receptor antagonist. Buprenorphine (BUP) is a partial opioid receptor agonist-antagonist, which limits overdose risk. BUP often is combined with NAL as a combination formulation, which is thought to reduce the repurposing of BUP for non-prescribed uses. At appropriate treatment dosages, both methadone (≥60 mg) and BUP (≥ 16 mg) are highly effective for the treatment of OUD.1 For patients with health insurance, pharmacy benefits often provide some coverage for preferred products but no coverage for other products. Not all pharmacies carry BUP products. In a study of more than 5,000 pharmacies, approximately 60% reported that they carry and can dispense BUP medications.2
BUP monotherapy is available as generic sublingual tablets, buccal films (Belbuca), formulations for injection (Sublocade), and subcutaneous implants (Probuphine). BUPNAL is available as buccal films (Bunavail), sublingual films (Suboxone), and sublingual tablets (Zubsolv). For BUP-NAL combination productions, the following dose combinations have been reported to have similar effects: BUP-NAL 8 mg/2 mg sublingual film, BUP-NAL 5.7 mg/1.4 mg sublingual tablet, and BUP-NAL 4.2 mg/0.7 mg buccal film.3
When initiating BUP-monotherapy or BUP-NAL treatment for OUD, one approach for unobserved initiation is to instruct the patient to discontinue using opioid agonist drugs and wait for the onset of mild to moderate withdrawal symptoms. The purpose of this step is to avoid precipitating severe withdrawal symptoms caused by giving BUP or BUP-NAL to a patient who has recently used opioid drugs.
If BUP-NAL sublingual films (Suboxone) are prescribed following the onset of mild to moderate withdrawal symptoms, the patient can initiate therapy with a dose of 2 mg BUP/0.5 mg NAL or 4 mg BUP/1 mg NAL. At 60 to 120 minutes following the initial dose, if withdrawal symptoms persist, an additional dose of 4 mg BUP/1 mg NAL can be given. Thereafter, symptoms can be assessed every 60 to 120 minutes and additional doses administered to control symptoms. On the second day of therapy, a maximum of 16 mg of BUP is administered. Over the following days and weeks, if symptoms and cravings persist at a BUP dose of 16 mg, the total daily dose of BUP can be titrated up to 24 mg. For long-term treatment, a commonly prescribed daily dose is 16 mg BUP/4 mg NAL or 24 mg BUP/6 mg NAL. An absolute contraindication to BUP or BUP/NAL treatment is an allergy to the medication, and a relative contraindication is liver failure.
One potential complication of transmucosal BUP or BUP-NAL treatment is a dry mouth (xerostomia), which may contribute to dental disease.4 However, some experts question the quality of the data that contributed to the warning.5,6 Potential dental complications might be prevented by regular oral health examinations, daily flossing and teeth brushing, and stimulation of saliva by sugar-free gum or lozenges.
Primary care clinicians who initiate BUP or BUPNAL treatment for OUD often have a weekly visit with the patient during the initial phase of treatment and then every 3 to 4 weeks during maintenance therapy. Most patients need long-term treatment to achieve the goals of therapy, which include prevention of opioid overdose, reduction of cravings for nonprescription narcotics, and improvement in overall health. BUP and BUP-NAL treatment are effective without formal counseling, but counseling and social work support improve long-term adherence with treatment. Primary care clinicians who have experience with medication treatment of OUD report that their experience convinces them that medication treatment of OUD has similarities to the long-term treatment of diabetes, with antihyperglycemia medicines or the treatment of HIV infection with antiviral medications.
References
1. Mattick RP, Breen C, Kimber J, et al. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;CD002207.
2. Weiner SG, Qato DM, Faust JS, et al. Pharmacy availability of buprenorphine for opioid use disorder treatment in the U.S. JAMA Netw Open. 2023;6:E2316089.
3. Substance Abuse and Mental Health Services Administration (SAMHSA). Medications for opioid use disorder. SAMHSA website. Accessed August 21, 2023. https ://store.samhsa.gov/sites/default/files/SAMHSA_Digital_Download/PEP 21-02-01-002.pdf
4. FDA warns about dental problems with buprenorphine medicines dissolved in the mouth. FDA website. Accessed August 21, 2023. https ://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-dental-problems-buprenorphine-medicines-dissolved-mouth-treat-opioiduse-disorder#:~:text=What%20did%20FDA%20find%3F,medicines%20 dissolved%20in%20the%20mouth
5. Watson DP, Etmian S, Gastala N. Sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2023;329:1223-1224.
6. Brothers TD, Lewer D, Bonn M. Sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2023;329:1224.
Medication treatment of OUD in obstetrics
In the United States, the prevalence of OUD among pregnant patients hospitalized for delivery more than quadrupled from 1999 through 2014.18 BUP and methadone commonly are used to treat OUD during pregnancy.19 Among pregnant patients about 5% of buprenorphine prescriptions are written by obstetricians.20 An innovative approach to initiating BUP for pregnant patients with OUD is to use unobserved initiation, which involves outpatient discontinuation of nonprescription opioids to induce mild to moderate withdrawal symptoms followed by initiation of BUP treatment. In one cohort study, 55 pregnant patients used an unobserved outpatient protocol to initiate BUP treatment; 80% of the patients previously had used methadone or BUP. No patient experienced a precipitated withdrawal and 96% of patients returned for their office visit 1 week after initiation of treatment. Eighty-six percent of patients remained in treatment 3 months following initiation of BUP.21
Compared with methadone, BUP treatment during pregnancy may result in lower rates of neonatal abstinence syndrome. In one study of pregnant patients who were using methadone (n = 5,056) or BUP (n = 11,272) in late pregnancy, neonatal abstinence syndrome was diagnosed in 69.2% and 52.0% of newborns, respectively (adjusted relative risk, 0.73; 95% confidence interval, 0.71–0.75).22 In addition, compared with methadone, the use of BUP was associated with a reduced risk for low birth weight (14.9% vs 8.3%) and a lower risk for preterm birth (24.9% vs 14.4%). In this study, there were no differences in maternal obstetric outcomes when comparing BUP versus methadone treatment. Similar results have been reported in a meta-analysis analyzing the use of methadone and BUP during pregnancy.23 Studies performed to date have not shown an increased risk of congenital anomalies with the use of BUP-NAL during pregnancy.24,25
Although there may be differences in newborn outcomes with BUP and methadone, the American College of Obstetricians and Gynecologists does not recommend switching from methadone to BUP during pregnancy because precipitated withdrawal may occur.26 Based on recent studies, the American Society of Addiction Medicine has advised that it is safe to prescribe pregnant patients either BUP or BUP-NAL.27,28
Medication treatment of OUD with or without intensive counseling
The FDA recently reviewed literature related to the advantages and challenges of combining intensive counseling with medication treatment of OUD.29 The FDA noted that treatment saves lives and encouraged clinicians to initiate medication treatment of OUD or refer the patient to an appropriate clinician or treatment center. Combining medication treatment of OUD with intensive counseling is associated with greater treatment adherence and reduced health care costs. For example, in one study of 4,987 patients with OUD, initiation of counseling within 8 weeks of the start of medication treatment and a BUP dose of 16 mg or greater daily were associated with increased adherence to treatment.30 For patients receiving a BUP dose of less than 16 mg daily, treatment adherence with and without counseling was approximately 325 and 230 days, respectively. When the dose of BUP was 16 mg or greater, treatment adherence with and without counseling was approximately 405 and 320 days, respectively.30
Counseling should always be offered to patients initiating medication treatment of OUD. It should be noted that counseling alone is not a highly effective treatment for OUD.31 The FDA recently advised that the lack of availability of intensive counseling should not prevent clinicians from initiating BUP for the treatment of OUD.29 OUD is associated with a high mortalityrate and if counseling is not possible, medication treatment should be initiated. Substantial evidence demonstrates that medication treatment of OUD is associated with many benefits.16 The FDA advisory committee concluded that OUD treatment decisions should use shared decision making and be supportive and patient centered.29
The opportunities for medication treatment of OUD in primary care practice have expanded due to the recent FDA removal of restrictions on the use of BUP and heightened awareness of the positive public health impact of medication treatment. Challenges to the medication treatment of OUD remain, including stigmatization of OUD, barriers to insurance coverage for BUP, practice costs of treating OUD, and gaps in clinical education. For many pregnant patients, their main point of contact with health care is their obstetrician. By incorporating OUD treatment in pregnancy care, obstetricians will improve the health of the mother and newborn, contributing to the well-being of current and future generations. ●
Interventions to reduce opioid overdose death
Experts have recommended several interventions that may help reduce opioid overdose death.1 A consensus recommendation is that people who use drugs should be provided naloxone rescue medication and educated on the proper use of naloxone. Naloxone rescue medication is available in formulations for nasal or parenteral administration. The US Food and Drug Administration (FDA) recently has approved naloxone for over-the-counter status. The American Medical Association has provided a short web video on how to administer nasal naloxone.2 In a small pilot study, obstetricians offered every postpartum patient with naloxone administration education and a 2-dose nasal naloxone pack, with 76% of patients accepting the nasal naloxone pack.3
Many experts recommend that people who use drugs should be advised to never use them alone and to test a small amount of the drug to assess its potency. Many patients who use opioid drugs also take benzodiazepines, which can contribute to respiratory depression.4 Patients should avoid mixing drugs (eg, opioids and benzodiazepines). Some experts recommend that patients who use drugs should be provided take-home fentanyl test strips so they can evaluate their drugs for the presence of fentanyl, a medication that suppresses respiration and contributes to many overdose deaths. In addition, people who use drugs and are interested in reducing their use of drugs or managing overdose risk can be offered initiation of medication treatment of OUD.1
References
1. Wood E, Solomon ED, Hadland SE. Universal precautions for people at risk of opioid overdose in North America. JAMA Int Med. 2023;183:401-402.
2. How to administer Naloxone. AMA website. Accessed August 28, 2023. https://www.ama-assn.org /delivering-care/overdose-epidemic/how-administer-naloxone
3. Naliboff JA, Tharpe N. Universal postpartum naloxone provision: a harm reduction quality improvement project. J Addict Med. 2022;17:360-362.
4. Kelly JC, Raghuraman N, Stout MJ, et al. Home induction of buprenorphine for treatment of opioid use disorder in pregnancy. Obstet Gynecol. 2021;138:655-659.