The Impact of Naloxone Coprescribing Mandates on Opioid-Involved Overdose Deaths

Published:December 08, 2022DOI:


      Since 2017, a total of 10 states have mandated naloxone coprescribing intended to prevent fatal opioid overdoses. This study aims to assess the association between naloxone coprescribing/offering mandates and opioid-involved overdose deaths on the basis of the opioid type.


      Data on overdose deaths from 1999 to 2020 came from the National Center for Health Statistics CDC WONDER Online Database. This study examined deaths stratified by illicit/synthetic opioids and prescription/treatment opioids. Difference-in-difference negative binomial regression models estimated average marginal effects and 95% CIs. Covariates included opioid dispensing rate, Good Samaritan law, pharmacy-based naloxone access law, mandatory use of prescription drug monitoring program, and recreational cannabis dispensaries. Data collection and analysis were conducted in 2022.


      Ten states implemented naloxone coprescribing/offering mandates during the period. Coprescribing/offering mandates significantly reduced the number of prescription/treatment overdose deaths by 8.61 per state per quarter (95% CI= –15.13, –2.09), a 16% reduction from the counterfactual estimates. Coprescribing/offering mandates did not significantly impact illicit/synthetic overdose deaths (average marginal effect=0.32; 95% CI= –18.27, 18.91).


      Coprescribing/offering mandates prevent overdose deaths for its target population, individuals using prescription/treatment opioids. These mandates do not appear to impact populations using illicit/synthetic opioids; thus, expanded efforts are needed to reach these individuals.
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      1. U.S. Overdose deaths in 2021 increased half as much as in 2020 - but are still up 15%.
        Centers for Disease Control and Prevention. 2022; (Updated May 11,Accessed June 11, 2022)
      2. Understanding the opioid overdose epidemic.
        Centers for Disease Control and Prevention. 2022; (Updated June 1. Accessed June 11, 2022)
        • Davis CS
        • Carr D
        Legal changes to increase access to naloxone for opioid overdose reversal in the United States.
        Drug Alcohol Depend. 2015; 157: 112-120
      3. Naloxone overdose prevention laws. Prescription Drug Abuse Policy System. 2022. Updated January 1. Accessed April 25, 2022.

        • Haffajee RL
        • Cherney S
        • Smart R
        Legal requirements and recommendations to prescribe naloxone.
        Drug Alcohol Depend. 2020; 209107896
        • Sohn M
        • Talbert JC
        • Huang Z
        • Lofwall MR
        • Freeman PR
        Association of naloxone coprescription laws with naloxone prescription dispensing in the United States.
        JAMA Netw Open. 2019; 2e196215
        • Green TC
        • Davis C
        • Xuan Z
        • Walley AY
        • Bratberg J
        Laws mandating coprescription of naloxone and their impact on naloxone prescription in five U.S. states, 2014–2018.
        Am J Public Health. 2020; 110: 881-887
      4. National vital statistics system, mortality; 1999–2020 on CDC WONDER Online Database. Data are from the Multiple Cause of Death Files, 1999-2020, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Centers for Disease Control and Prevention, National Center for Health Statistics. 2022. Updated January 6. Accessed February 6, 2022.

        • Lee B
        • Zhao W
        • Yang KC
        • Ahn YY
        • Perry BL
        Systematic evaluation of state policy interventions targeting the U.S. opioid epidemic, 2007–2018.
        JAMA Netw Open. 2021; 4e2036687
      5. AG Grewal announces four regulatory actions addressing New Jersey’s opioid addiction epidemic. Newly adopted rule requires doctors to co-prescribe naloxone to patients at risk of overdose.
        New Jersey Division of Consumer Affairs. 2021; (Published February 19. Accessed April 25, 2022)
        • Abouk R
        • Pacula RL
        • Powell D.
        Association between state laws facilitating pharmacy distribution of naloxone and risk of fatal overdose.
        JAMA Intern Med. 2019; 179: 805-811
        • Lieberman A
        • Davis C.
        Legal interventions to reduce overdose mortality: overdose Good Samaritan laws.
        Edina, MN: The Network for Public Health Law. 2021; (Published August 18,Accessed April 25, 2022)
        • Rudolph KE
        • Gimbrone C
        • Matthay EC
        • et al.
        When effects cannot be estimated: redefining estimands to understand the effects of naloxone access laws.
        Epidemiology. 2022; 33: 689-698
        • Erfanian E
        • Grossman D
        • Collins AR.
        The impact of naloxone access laws on opioid overdose deaths in the U.S.
        Rev Reg Stud. 2019; 49: 45-72
        • McClellan C
        • Lambdin BH
        • Ali MM
        • et al.
        Opioid-overdose laws association with opioid use and overdose mortality.
        Addict Behav. 2018; 86: 90-95
        • Rees DI
        • Sabia JJ
        • Argys LM
        • Dave D
        • Latshaw J
        With a little help from my friends: the effects of Good Samaritan and naloxone access laws on opioid-related deaths.
        J Law Econ. 2019; 62: 1-27
        • Smart R
        • Pardo B
        • Davis CS
        Systematic review of the emerging literature on the effectiveness of naloxone access laws in the United States.
        Addiction. 2021; 116: 6-17
        • Livingston MD
        • Barnett TE
        • Delcher C
        • Wagenaar AC.
        Recreational cannabis legalization and opioid-related deaths in Colorado, 2000–2015.
        Am J Public Health. 2017; 107: 1827-1829
        • Kvamme SL
        • Pedersen MM
        • Rømer Thomsen K
        • Thylstrup B
        Exploring the use of cannabis as a substitute for prescription drugs in a convenience sample.
        Harm Reduct J. 2021; 18: 72
        • Lucas P
        • Baron EP
        • Jikomes N.
        Medical cannabis patterns of use and substitution for opioids & other pharmaceutical drugs, alcohol, tobacco, and illicit substances; results from a cross-sectional survey of authorized patients.
        Harm Reduct J. 2019; 16: 9
        • Noori A
        • Miroshnychenko A
        • Shergill Y
        • et al.
        Opioid-sparing effects of medical cannabis or cannabinoids for chronic pain: a systematic review and meta-analysis of randomised and observational studies.
        BMJ Open. 2021; 11e047717
        • Reiman A
        • Welty M
        • Solomon P.
        Cannabis as a substitute for opioid-based pain medication: patient self-report.
        Cannabis Cannabinoid Res. 2017; 2: 160-166
      6. U.S. Opioid dispensing rate maps.
        Centers for Disease Control and Prevention. 2021; (Updated November 10,Accessed April 25, 2022)
        • StataCorp
        Stata Statistical Software: Release 16.
        StataCorp LP, College Station, TX2016
        • Xu J
        • Davis CS
        • Cruz M
        • Lurie P.
        State naloxone access laws are associated with an increase in the number of naloxone prescriptions dispensed in retail pharmacies.
        Drug Alcohol Depend. 2018; 189: 37-41
        • Sohn M
        • Delcher C
        • Hankosky ER
        • Lofwall MR
        • Freeman PR
        Association between state Medicaid expansion status and naloxone prescription dispensing.
        Health Serv Res. 2020; 55: 239-248
        • Freeman PR
        • Hankosky ER
        • Lofwall MR
        • Talbert JC
        The changing landscape of naloxone availability in the United States, 2011–2017.
        Drug Alcohol Depend. 2018; 191: 361-364
        • Ong AR
        • Lee S
        • Bonar EE
        Understanding disparities in access to naloxone among people who inject drugs in Southeast Michigan using respondent driven sampling.
        Drug Alcohol Depend. 2020; 206107743
      7. Fomiatti R, Farrugia A, Fraser S, Dwyer R, Neale J, Strang J. Addiction stigma and the production of impediments to take-home naloxone uptake. Health (London). 2022;26(2):139–161.

        • Spivey CA
        • Wilder A
        • Chisholm-Burns MA
        • Stallworth S
        • Wheeler J
        Evaluation of naloxone access, pricing, and barriers to dispensing in Tennessee retail community pharmacies.
        J Am Pharm Assoc (2003). 2020; 60 (e1): 694-701
        • Thornton JD
        • Lyvers E
        • Scott VGG
        • Dwibedi N.
        Pharmacists’ readiness to provide naloxone in community pharmacies in West Virginia.
        J Am Pharm Assoc (2003). 2017; 57 (e4): S1-S18
        • Donovan E
        • Case P
        • Bratberg JP
        • et al.
        Beliefs associated with pharmacy-based naloxone: a qualitative study of pharmacy-based naloxone purchasers and people at risk for opioid overdose.
        J Urban Health. 2019; 96: 367-378
        • Cheetham A
        • Picco L
        • Barnett A
        • Lubman DI
        • Nielsen S.
        The impact of stigma on people with opioid use disorder, opioid treatment, and policy.
        Subst Abuse Rehabil. 2022; 13: 1-12
        • Meyerson BE
        • Agley JD
        • Davis A
        • et al.
        Predicting pharmacy naloxone stocking and dispensing following a statewide standing order, Indiana 2016.
        Drug Alcohol Depend. 2018; 188: 187-192
        • Freeman PR
        • Goodin A
        • Troske S
        • Strahl A
        • Fallin A
        • Green TC
        Pharmacists’ role in opioid overdose: Kentucky pharmacists’ willingness to participate in naloxone dispensing.
        J Am Pharm Assoc. 2017; 57: S28-S33
        • Zaller ND
        • Yokell MA
        • Green TC
        • Gaggin J
        • Case P
        The feasibility of pharmacy-based naloxone distribution interventions: a qualitative study with injection drug users and pharmacy staff in Rhode Island.
        Subst Use Misuse. 2013; 48: 590-599
        • Watson DP
        • Ray B
        • Robison L
        • et al.
        Lay responder naloxone access and Good Samaritan law compliance: postcard survey results from 20 Indiana counties.
        Harm Reduct J. 2018; 15: 18
        • Olson R
        Law that protects 911 callers in overdoses doesn’t preclude evidence gathering, court rules.
        StarTribune. February 10, 2020; (Accessed May 10, 2022)
        • Castillo-Carniglia A
        • Ponicki WR
        • Gaidus A
        • et al.
        Prescription drug monitoring programs and opioid overdoses: exploring sources of heterogeneity.
        Epidemiology. 2019; 30: 212-220
        • Islam MM
        • McRae IS
        An inevitable wave of prescription drug monitoring programs in the context of prescription opioids: pros, cons and tensions.
        BMC Pharmacol Toxicol. 2014; 15: 46
        • Allen B
        • Harocopos A
        • Chernick R
        Substance use stigma, primary care, and the New York State prescription drug monitoring program.
        Behav Med. 2020; 46: 52-62
        • Picco L
        • Lam T
        • Haines S
        • Nielsen S
        How prescription drug monitoring programs influence clinical decision-making: a mixed methods systematic review and meta-analysis.
        Drug Alcohol Depend. 2021; 228109090
        • Walley AY
        • Xuan Z
        • Hackman HH
        • et al.
        Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.
        BMJ. 2013; 346: f174
        • Bird SM
        • McAuley A
        • Perry S
        • Hunter C.
        Effectiveness of Scotland's National naloxone Programme for reducing opioid-related deaths: a before (2006–10) versus after (2011–13) comparison.
        Addiction. 2016; 111: 883-891
        • Keane C
        • Egan JE
        • Hawk M.
        Effects of naloxone distribution to likely bystanders: results of an agent-based model.
        Int J Drug Policy. 2018; 55: 61-69
        • Winhusen T
        • Walley A
        • Fanucchi LC
        • et al.
        The Opioid-overdose Reduction Continuum of Care Approach (ORCCA): evidence-based practices in the HEALing Communities Study.
        Drug Alcohol Depend. 2020; 217108325
        • Huff C
        Confronting an opioid crisis and promoting health from all angles.
        Health Aff (Millwood). 2020; 39: 1861-1866
        • Green TC
        • Bratberg J
        • Irwin AN
        • et al.
        Study protocol for the Respond to Prevent Study: a multi-state randomized controlled trial to improve provision of naloxone, buprenorphine and nonprescription syringes in community pharmacies.
        Subst Abus. 2022; 43: 901-905
        • McQuillan A
        Clinical pharmacist involvement in expanding naloxone distribution in a veteran population.
        Am J Health Syst Pharm. 2022; 79: 472-476
        • Cooper EN
        • Dodson C
        • Stopka TJ
        • Riley ED
        • Garfein RS
        • Bluthenthal RN
        Pharmacy participation in non-prescription syringe sales in los Angeles and San Francisco counties, 2007.
        J Urban Health. 2010; 87: 543-552
        • Rudolph AE
        • Crawford ND
        • Ompad DC
        • Benjamin EO
        • Stern RJ
        • Fuller CM
        Comparison of injection drug users accessing syringes from pharmacies, syringe exchange programs, and other syringe sources to inform targeted HIV prevention and intervention strategies.
        J Am Pharm Assoc (2003). 2010; 50: 140-147
        • Delcher C
        • Harris DR
        • Anthony N
        • Mir M.
        Opioid overdoses increase at home during the COVID-19 stay-at-home order period in Cook County, Illinois.
        AJPM Focus. 2022; 1100007
        • Hedegaard H
        • Miniño AM
        • Spencer MR
        • Warner M
        Drug overdose deaths in the United States, 1999–2020.
        NCHS Data Brief. 2021; 428: 1-8
        • Glick SN
        • Prohaska SM
        • LaKosky PA
        • Juarez AM
        • Corcorran MA
        • Des Jarlais DC
        The impact of COVID-19 on syringe services programs in the United States.
        AIDS Behav. 2020; 24: 2466-2468
        • Linas BP
        • Savinkina A
        • Barbosa C
        • et al.
        A clash of epidemics: impact of the COVID-19 pandemic response on opioid overdose.
        J Subst Abuse Treat. 2021; 120108158
        • Dunlop A
        • Lokuge B
        • Masters D
        • et al.
        Challenges in maintaining treatment services for people who use drugs during the COVID-19 pandemic.
        Harm Reduct J. 2020; 17: 26
        • Mason M
        • Welch SB
        • Arunkumar P
        • Post LA
        • Feinglass JM.
        Notes from the field: opioid overdose deaths before, during, and after an 11-week COVID-19 stay-at-home order – Cook County, Illinois, January 1, 2018-October 6, 2020.
        MMWR Morb Mortal Wkly Rep. 2021; 70: 362-363