Methadone-Involved Overdose Deaths Before and After Expanding Take-Home Methadone Doses (2024)

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Research Letter

Christopher M.Jones,PharmD, DrPH1; Wilson M.Compton,MD, MPE2; BethHan,MD, PhD, MPH2; et al GrantBaldwin,PhD, MPH1; Nora D.Volkow,MD2

Author Affiliations Article Information

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.

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.

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).

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.

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.