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Figure.  Monthly Overdose Deaths With and Without Methadone, United States, January 2019 to August 2021
Monthly Overdose Deaths With and Without Methadone, United States, January 2019 to August 2021

Opioid treatment program methadone take-home policy was released by the Substance Abuse and Mental Health Services Administration on March 16, 2020. Source: National Vital Statistics System, Multiple-Cause-of-Death Final 2019-2020 Data and Provisional 2021 Data.

Table.  Interrupted Time Series Analysis Estimates for Monthly Overdose Deaths With and Without Methadone, United States, January 2019 to August 2021
Interrupted Time Series Analysis Estimates for Monthly Overdose Deaths With and Without Methadone, United States, January 2019 to August 2021
1.
Substance Abuse and Mental Health Services Administration. Methadone take-home flexibilities extension guidance. Updated March 3, 2021. Accessed March 15, 2022. https://www.samhsa.gov/medication-assisted-treatment/statutes-regulations-guidelines/methadone-guidance
2.
Jones  CM, Baldwin  GT, Manocchio  T, White  JO, Mack  KA.  Trends in methadone distribution for pain treatment, methadone diversion, and overdose deaths: United States, 2002-2014.   MMWR Morb Mortal Wkly Rep. 2016;65(26):667-671. doi:10.15585/mmwr.mm6526a2PubMedGoogle ScholarCrossref
3.
O’Donnell  J, Tanz  LJ, Gladden  RM, Davis  NL, Bitting  J.  Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls: United States, 2019-2020.   MMWR Morb Mortal Wkly Rep. 2021;70(50):1740-1746. doi:10.15585/mmwr.mm7050e3PubMedGoogle ScholarCrossref
4.
Brothers  S, Viera  A, Heimer  R.  Changes in methadone program practices and fatal methadone overdose rates in Connecticut during COVID-19.   J Subst Abuse Treat. 2021;131:108449. doi:10.1016/j.jsat.2021.108449PubMedGoogle ScholarCrossref
5.
Amram  O, Amiri  S, Panwala  V, Lutz  R, Joudrey  PJ, Socias  E.  The impact of relaxation of methadone take-home protocols on treatment outcomes in the COVID-19 era.   Am J Drug Alcohol Abuse. 2021;47(6):722-729. doi:10.1080/00952990.2021.1979991PubMedGoogle ScholarCrossref
6.
McIlveen  JW, Hoffman  K, Priest  KC, Choi  D, Korthuis  PT, McCarty  D.  Reduction in Oregon’s medication dosing visits after the SARS-CoV-2 relaxation of restrictions on take-home medication.   J Addict Med. 2021;15(6):516-518. doi:10.1097/ADM.0000000000000812PubMedGoogle ScholarCrossref
2 Comments for this article
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Strong evidence for expanding take-home methadone limits for OUD pts
Devin Hosea, AB | King's College London
I think it has been well documented that methadone is the "gold standard" for opioid substitution treatment (OST) or medication assisted treatment (MAT) or whichever term one wishes to use. These data clearly show that the expansion of take-home methadone, even to "less stable" patients, did not materially increase mortality. Furthermore, with the exception of one month (March 2020), this expansion seems to have actually decreased mortality when considered against the backdrop of a large rise in opioid-related deaths in 2020 and 2021.

Another consideration is that such an expansion would make methadone accessible to pts
for whom it is now not a practical option, because as the authors state, "...most patients historically receive methadone daily from OTPs". For many patients, a daily trip to the methadone clinic represents a severe burden and discourages them from induction and adherence to a methadone treatment protocol. Put simply, buprenorphine is now the only option available to a vast swath of patients, when the historical data show that methadone is a better medication (at least from a mortality-prevention standpoint). Permanently relaxing the take-home methadone requirements would at a minimum give addiction medicine physicians another option to offer their pts, and an important alternative for pts who do not respond to buprenorphine or tolerate it well.

This policy modification, of course, should be balanced against the benefits of seeing patients at the clinic on a frequent basis. Obviously, take-home methadone protocols need to be personalized to the pt. But that personalization should be done by the treating physician, not by a broad edict that historically has discouraged access and adherence to methadone by the de-facto requirement of daily visits. This is an important finding.

Devin Hosea
Visiting Research Fellow
Department of Addiction Science
Institute for Psychiatry, Psychology and Neuroscience
King's College London
devin.hosea@kcl.ac.uk
CONFLICT OF INTEREST: None Reported
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Letter to the Editor: PDMPs as it relates to OTPs and Expanded Take-Home Policies
Alexis Rojas, Ph.D. | Department of Surgery, University of Florida, Jacksonville, Florida
The intention of this letter is to respond to the article titled Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses from Opioid Treatment Programs 1 by recognizing the important work the article highlights regarding flexible opioid treatment programs (OTP) practices to meet patient needs. However, it also serves as encouragement for multidisciplinary professionals to promote the utilization of Prescription Drug Monitoring Programs (PDMP) as it relates to OTPs, specifically methadone. Such advocacy is intended to increase the safety of the patients and the providers. The ongoing public health tragedy surrounding the opioid crisis demands closer monitoring of prescribing practices. In 2018, nearly 47,000 opioid-related deaths were reported in the United States, which is nearly six times greater than in 1999.2 Specifically, one suspected high risk of death from opioids exists when full opioid agonists, such as methadone, are used in combination with illicit or unknown co-prescribed opioids.3

PDMPs are statewide electronic databases that collect data related to the dispensing of controlled substances. The intent of the PDMPs are to promote safe prescribing practices by informing prescribers of controlled substance usage. A well-known limitation of the PDMPs is the absence of methadone reporting by OTPs. The reporting of such information is considered a violation of protected addiction treatment records (per 42 CFR Part 2), yet is critical for safe prescribing and monitoring practices, especially when considering take-home blanket exemptions.

As recommended by the American Society of Addiction Medicine (ASAM), states should expand PDMP reportable medications to include both methadone and buprenorphine from OTPs.4 In clinical practice, patients may be at greater risk when receiving treatment from an OTP while also receiving treatment by pain management physician.5 Such instances can result in injury or death to the patient and high emotional and legal liability for the prescriber and dispenser. We encourage state and national representatives, with support from the medical community, to establish a middle ground between patient privacy and safety. We believe the current take-home blanket exemptions have elevated the need for improved prescribing transparency because of the limited direct supervision a patient might receive with take-home prescribing.

References
1. Jones CM, Compton WM, Han B, Baldwin G, Volkow ND. Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses From Opioid Treatment Programs. JAMA Psychiatry. 2022;79(9):932–934.
2. Hedegaard H, Miniño AM, Warner M. Drug Overdose Deaths in the United States, 1999-2018 Key Findings Data from the National Vital Statistics System, Mortality.; 1999.
3. Nosyk B, Fischer B, Sun H, et al. High levels of opioid analgesic co-prescription among methadone maintenance treatment clients in British Columbia, Canada: Results from a population-level retrospective cohort study. American Journal on Addictions. 2014;23(3):257-264.
4. Public Policy Statement on Morphine Equivalent Units/Morphine Milligram Equivalents Background. Published online 2016.
5. Jones CM, Baldwin GT, Manocchio T, White JO, Mack KA. Trends in Methadone Distribution for Pain Treatment, Methadone Diversion, and Overdose Deaths — United States, 2002–2014. MMWR Morb Mortal Wkly Rep 2016;65:667–671.

AM Rojas, PR Worts, and GS Chandler III
CONFLICT OF INTEREST: None Reported
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Research Letter
July 13, 2022

Methadone-Involved Overdose Deaths in the US Before and After Federal Policy Changes Expanding Take-Home Methadone Doses From Opioid Treatment Programs

Author Affiliations
  • 1National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
  • 2National Institute on Drug Abuse, National Institutes of Health, Bethesda, Maryland
JAMA Psychiatry. 2022;79(9):932-934. doi:10.1001/jamapsychiatry.2022.1776

On March 16, 2020, to facilitate access to methadone treatment from opioid treatment programs (OTPs) during the COVID-19 pandemic, the Substance Abuse and Mental Health Services Administration allowed states to request blanket exceptions to provide up to 28 and 14 days of take-home methadone for stable and less stable patients, respectively; this signaled a shift in practice because most patients historically receive methadone daily from OTPs.1

Prior research indicates most methadone-involved overdose deaths are due to methadone used for pain rather than opioid use disorder treatment.2 It is unknown whether methadone-involved overdose deaths increased owing to expanded OTP take-home policies.

Methods

US Centers for Disease Control and Prevention National Vital Statistics System multiple cause of death 2019-2020 final and 2021 provisional data were used. Drug overdose deaths were those assigned an underlying cause of death (ICD-10 codes X40-X44, X60-X64, X85, and Y10-Y14; methadone-involved deaths had ICD-10 code T40.3). Overdose deaths could involve multiple drugs.

Monthly drug overdose deaths without involving methadone and methadone-involved and percentages of overdose deaths involving methadone during January 2019 to August 2021 were calculated. Interrupted time series analyses (ITSA) assessed changes in outcomes before/after the March 2020 methadone take-home policy. This study was exempt from institution review board review by regulation. Stata version 16 (StataCorp) ITSA program was used for analyses. P values less than .05 (2-sided) were considered statistically significant.

Results

ITSA-estimated monthly overdose deaths without involving methadone increased by 78.12 (95% CI, 53.69-102.55; P < .001) deaths per month before March 2020, by 1078.27 (95% CI, 410.08-1746.46; P = .003) deaths in March 2020, and by 69.07 (95% CI, 15.45-122.70; P = .01) deaths per month after March 2020 (Figure and Table). Trend slopes were similar before and after March 2020 (−9.05 [95% CI, −67.98 to 49.88]; P = .76).

Before March 2020, ITSA-estimated methadone-involved overdose deaths were stable (−0.12 [95% CI, −2.54 to 2.29; P = .92) (Figure and Table). Consistent with the increase in overdose deaths without involving methadone, methadone-involved overdose deaths increased by 94.12 (95% CI, 45.38-142.86; P < .001) deaths in March 2020. Monthly methadone-involved overdose deaths remained stable after March 2020 (−1.91 [95% CI, −5.50 to 1.68]; P = .29). Trend slopes were similar before and after March 2020 (−1.79 [95% CI, −6.11 to 2.54]; P = .41).

ITSA-estimated percentages of overdose deaths involving methadone declined 0.06% (95% CI, −0.10% to 0.01%; P = .02) per month before March 2020, increased by 0.69% (95% CI, 0.22%-1.15%; P = .006) in March 2020, and declined 0.05% per month (95% CI, −0.08% to 0.02%; P = .001) after March 2020. Trend slopes were similar before and after March 2020 (0.01% [95% CI, −0.05% to 0.06%]; P = .82).

Discussion

Findings provide insights about methadone-involved overdose deaths during COVID-19. In March 2020, overdose deaths both with and without methadone increased. After March 2020, overdose deaths not involving methadone continued to increase approximately 69 deaths per month, whereas methadone-involved overdose deaths remained stable. The percentage of overdose deaths involving methadone declined at similar rates, approximately 0.05% to 0.06%, before and after the take-home policy change, with 4.5% of overdose deaths involving methadone in January 2019 and declining to 3.2% by August 2021. These findings suggest the modest increase in methadone-involved overdose deaths in March 2020 was associated with the spike in overall drug overdose deaths driven by illicitly made fentanyl in the early months of the COVID-19 pandemic3 rather than associated with OTP take-home policy changes.

This study has limitations. Approximately 5% of death certificates did not list specific drugs involved in the overdose. Provisional data for 2021 may minimally underestimate overdose deaths owing to delayed reporting. OTP take-home policy changes occurred in the context of other policy changes and secular trends that could influence treatment and harms for people with opioid use disorder.

Coupled with research demonstrating improved patient satisfaction, treatment access, and engagement from these policies,1,4-6 these findings can inform decisions about permanently expanding take-home methadone.

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Article Information

Corresponding Author: Christopher M. Jones, PharmD, DrPH, National Center for Injury Prevention and Control, 4770 Buford Highway NE, Atlanta, GA 30341 (fjr0@cdc.gov).

Accepted for Publication: May 16, 2022.

Published Online: July 13, 2022. doi:10.1001/jamapsychiatry.2022.1776

Author Contributions: Dr Jones had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Jones, Compton, Volkow.

Acquisition, analysis, or interpretation of data: Jones, Compton, Han, Baldwin.

Drafting of the manuscript: Jones, Baldwin.

Critical revision of the manuscript for important intellectual content: Compton, Han, Baldwin, Volkow.

Statistical analysis: Jones.

Administrative, technical, or material support: Jones, Volkow.

Supervision: Volkow.

Conflict of Interest Disclosures: Dr Compton reported long-term stock holdings from General Electric Co, 3M Companies, and Pfizer Inc outside the submitted work. No other disclosures were reported.

Funding/Support: This study was sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health.

Role of the Funder/Sponsor: The sponsors supported the authors who were responsible for preparation, review, and approval of the manuscript and the decision to submit the manuscript for publication. The sponsors had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The sponsors reviewed and approved the manuscript.

Disclaimers: The findings and conclusions of this study are those of the authors and do not necessarily reflect the views of the National Institute on Drug Abuse of the National Institutes of Health, the Centers for Disease Control and Prevention, and the US Department of Health and Human Services.

References
1.
Substance Abuse and Mental Health Services Administration. Methadone take-home flexibilities extension guidance. Updated March 3, 2021. Accessed March 15, 2022. https://www.samhsa.gov/medication-assisted-treatment/statutes-regulations-guidelines/methadone-guidance
2.
Jones  CM, Baldwin  GT, Manocchio  T, White  JO, Mack  KA.  Trends in methadone distribution for pain treatment, methadone diversion, and overdose deaths: United States, 2002-2014.   MMWR Morb Mortal Wkly Rep. 2016;65(26):667-671. doi:10.15585/mmwr.mm6526a2PubMedGoogle ScholarCrossref
3.
O’Donnell  J, Tanz  LJ, Gladden  RM, Davis  NL, Bitting  J.  Trends in and characteristics of drug overdose deaths involving illicitly manufactured fentanyls: United States, 2019-2020.   MMWR Morb Mortal Wkly Rep. 2021;70(50):1740-1746. doi:10.15585/mmwr.mm7050e3PubMedGoogle ScholarCrossref
4.
Brothers  S, Viera  A, Heimer  R.  Changes in methadone program practices and fatal methadone overdose rates in Connecticut during COVID-19.   J Subst Abuse Treat. 2021;131:108449. doi:10.1016/j.jsat.2021.108449PubMedGoogle ScholarCrossref
5.
Amram  O, Amiri  S, Panwala  V, Lutz  R, Joudrey  PJ, Socias  E.  The impact of relaxation of methadone take-home protocols on treatment outcomes in the COVID-19 era.   Am J Drug Alcohol Abuse. 2021;47(6):722-729. doi:10.1080/00952990.2021.1979991PubMedGoogle ScholarCrossref
6.
McIlveen  JW, Hoffman  K, Priest  KC, Choi  D, Korthuis  PT, McCarty  D.  Reduction in Oregon’s medication dosing visits after the SARS-CoV-2 relaxation of restrictions on take-home medication.   J Addict Med. 2021;15(6):516-518. doi:10.1097/ADM.0000000000000812PubMedGoogle ScholarCrossref
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