Good month. 40 papers. I think the main takeaway here is the buprenorphine waiver required for U.S. providers to treat their patients with buprenorphine – it needs to go. It is an archaic and absurd construct essentially invented by the US Supreme Court a century ago when the court decided “addiction is not a disease”. It is well beyond time to treat substance use disorders as health problems.
Thanks again to Rebecca Martinez, Cathleen Beliveau, Nataliya Karashchuk, and Laila Esfandiari at the Center on Substance Use and Health (www.csuhsf.org) for collaborating to produce these summaries!
1) Pharmacist roles, training, and perceived barriers in naloxone dispensing: A systematic review.
Thakur T, Frey M, Chewning B.
J Am Pharm Assoc (2003). 2019 Jul 29. pii: S1544-3191(19)30320-6. doi: 10.1016/j.japh.2019.06.016. [Epub ahead of print] Review.
Comments: Legal, but underutilized. There’s an interesting difference between obtaining naloxone at syringe access programs versus pharmacies. Cost. The welcoming nature of syringe access programs (when they are run right). Stigma.
2) Opioid Overdose Hospitalization Trajectories in States With and Without Opioid-Dosing Guidelines.
Sears JM, Fulton-Kehoe D, Schulman BA, Hogg-Johnson S, Franklin GM.
Public Health Rep. 2019 Jul 31:33354919864362. doi: 10.1177/0033354919864362. [Epub ahead of print]
Comments: Tough analysis. And one that probably couldn’t be done today due to the geographic variability in fentanyl availability. They compared Colorada/Utah/Washington (as states with opioid prescribing guidelines) to Arizona/California/Michigan/New Jersey/South Carolina (as states without) from 2001-2014 to see what happened with opioid overdose hospitalizations. Of note, their state selection criteria did not include any assessment of similarity in opioid or drug use trends. Looking at the trendlines, it looks like the primary difference is that it took an extra 2 years for the curves to flatten in comparator states. Unknown if this corresponded to a decrease in overdose mortality.
Spada M, Kmiec J, Glance JB, Gopalan P.
Subst Abus. 2019 Jul 30:1-5. doi: 10.1080/08897077.2019.1635970. [Epub ahead of print]
Comments: Yes.
4) Who receives naloxone from emergency medical services? Characteristics of calls and recent trends.
Geiger C, Smart R, Stein BD.
Subst Abus. 2019 Jul 30:1-8. doi: 10.1080/08897077.2019.1640832. [Epub ahead of print]
Comments: Big increases in urban counties and among youth as fentanyl emerged. More multi-dose administrations. More refusal of transport. The West stands out in less of these trends, likely related to the delayed entrance of a significant street fentanyl market.
Strang J, McDonald R, Campbell G, Degenhardt L, Nielsen S, Ritter A, Dale O.
Drugs. 2019 Jul 27. doi: 10.1007/s40265-019-01154-5. [Epub ahead of print] Review.
Comments: Review.
Colledge S, Peacock A, Leung J, Larney S, Grebely J, Hickman M, Cunningham E, Trickey A, Stone J, Vickerman P, Degenhardt L.
Int J Drug Policy. 2019 Jul 24. pii: S0955-3959(19)30208-7. doi: 10.1016/j.drugpo.2019.07.030. [Epub ahead of print] Review.
Comments: Interesting approach – they determined that 20.5% and 41.5% of PWID have had a past year and lifetime overdose, respectively. The old back-of-the-napkin estimate was about 15% and 50%, respectively. I wonder how this applies though in fentanyl areas.
Queeneth U, Bhimanadham NN, Mainali P, Onyeaka HK, Pankaj A, Patel RS.
Behav Sci (Basel). 2019 Jul 13;9(7). pii: E77. doi: 10.3390/bs9070077.
Comments: The authors report that prescription opioids led to heroin use, although the data are from 2010-2014, and more recent data suggests that’s no longer the most common pathway.
Davis CS, Carr DH.
Int J Drug Policy. 2019 Jul 20;73:42-48. doi: 10.1016/j.drugpo.2019.07.006. [Epub ahead of print]
Comments: Yes – there’s an urgent need to get rid of many of the regulatory barriers – such as the only “waiver” ever required to treat a disease. This actually harkens back to the 1914 Harrison Narcotics Act and the subsequent determination by the US Supreme Court that “addiction is not a disease” … what a mess.
Reed M, Wagner KD, Tran NK, Brady KA, Shinefeld J, Roth A.
Int J Drug Policy. 2019 Jul 20;73:32-35. doi: 10.1016/j.drugpo.2019.07.010. [Epub ahead of print]
Comments: Syringe access programs.
10) Urban, individuals of color are impacted by fentanyl-contaminated heroin.
Rhodes B, Costenbader B, Wilson L, Hershow R, Carroll J, Zule W, Golin C, Brinkley-Rubinstein L.
Int J Drug Policy. 2019 Jul 19;73:1-6. doi: 10.1016/j.drugpo.2019.07.008. [Epub ahead of print]
Comments: Yep, this is the change that is less interesting to press…
McLean K, Kavanaugh PR.
Int J Drug Policy. 2019 Jul 19;71:118-124. doi: 10.1016/j.drugpo.2019.06.019. [Epub ahead of print]
Comments: Federal policies limit access, and funds poured into expanding access may not be reaching those it needs to reach.
12) Themes in published obituaries of people who have died of opioid overdose.
Rajesh K, Crijns TJ, Ring D.
J Addict Dis. 2019 Jul 22:1-6. doi: 10.1080/10550887.2019.1639485. [Epub ahead of print]
Comments: I can’t access the full article but would love to. The themes are love, joy, and sadness. No surprise here. People love people who use drugs.
13) Misperceptions about the ‘Opioid Epidemic:’ Exploring the Facts.
Oliver JE, Carlson C.
Pain Manag Nurs. 2019 Jul 18. pii: S1524-9042(19)30072-4. doi: 10.1016/j.pmn.2019.05.004. [Epub ahead of print] Review.
Comments: I can’t access the full article. They list misperceptions.
14) One single large intramuscular dose of naloxone is effective and safe in suspected heroin poisoning.
Harris K, Page CB, Samantray S, Parker L, Brier AJ, Isoardi KZ.
Emerg Med Australas. 2019 Jul 21. doi: 10.1111/1742-6723.13344. [Epub ahead of print]
Comments: Perhaps a large (1.6mg IM in this study) IM dose reduces the likelihood of more complex management in an emergency department. It’s important to see this in the context of the old days, when paramedics would routinely given large naloxone doses, often seen as a “punishment” of a person for experiencing an overdose. The transition to 0.4mg IM was considered humane – the shift back to high dose needs to be considered seriously before being implemented because EMS has access to the means to support respiration, making immediate and full reversal of overdose less important, or – in some circumstances – undesired.
15) Impact of a pharmacist-driven intervention on the outpatient dispensing of naloxone.
Griffin S, Wishart B, Bricker K, Luebchow A.
J Am Pharm Assoc (2003). 2019 Jul – Aug;59(4S):S161-S166. doi: 10.1016/j.japh.2019.06.011.
Comments: Pharmacists were able to convince more patients to accept naloxone prescriptions.
16) Deploying science to change hearts and minds: Responding to the opioid crisis.
Walsh SL, Long KQX.
Prev Med. 2019 Jul 15:105780. doi: 10.1016/j.ypmed.2019.105780. [Epub ahead of print]
Comments: The abstract calls for increased access to evidence-based care for people with opioid use disorder and identifies some barriers to treatment. Full text not available through Elsevier.
17) Heroin and healthcare: patient characteristics and healthcare prior to overdose.
Bohm MK, Bridwell L, Zibbell JE, Zhang K.
Am J Manag Care. 2019 Jul;25(7):341-347.
Comments: Interesting use of data from the IBM MarketScan Databases (insurance claims-based data set with millions of de-identified patient records) comparing annual heroin overdose rates between Medicaid and commercially-insured patients in the U.S. from 2010-2014. Heroin overdose was much more frequent among Medicaid compared to commercially-insured patients, with the exception of 15-24 year old persons. Over the four years, heroin overdose rates increased more rapidly for commercially-insured patients (270%) compared to Medicaid patients (94%), despite the fact that fewer commercially-insured patients had received prior opioid prescriptions in the month prior to overdose.
Bounthavong M, Devine EB, Christopher MLD, Harvey MA, Veenstra DL, Basu A.
Health Serv Res. 2019 Jul 17. doi: 10.1111/1475-6773.13194. [Epub ahead of print]
Comments: Efforts to implement academic detailing on opioid overdose and naloxone distribution have not been uniform across all VA stations. This study found that VA stations where 100% of providers were exposed to an academic detailing intervention had a naloxone prescribing rate that was 5.52 times that of stations where no providers were exposed.
Gicquelais RE, Mezuk B, Foxman B, Thomas L, Bohnert ASB.
Harm Reduct J. 2019 Jul 16;16(1):46. doi: 10.1186/s12954-019-0317-3.
Comments: Examines overdose education and naloxone distribution (OEND) engagement of individuals diverted from the criminal justice system to addiction treatment. Just over half correctly identified naloxone as an opioid overdose treatment, while 68% had experienced an overdose and 79% had witnessed another person overdose.
20) Supervised consumption sites: a nuanced assessment of the causal evidence.
Caulkins JP, Pardo B, Kilmer B.
Addiction. 2019 Jul 16. doi: 10.1111/add.14747. [Epub ahead of print]
Comments: Review article describing evidence around supervised consumption sites (SCS). Posits that the nature of such studies often precludes causal evidence, but that the literature generally shows associations between SCS and positive client outcomes.
Darracq MA, Lee J, Wilson T, Lasoff D, Armenian P.
Int J Drug Policy. 2019 Jul 10;71:113-117. doi: 10.1016/j.drugpo.2019.06.001. [Epub ahead of print]
Comments: Since AB1535 was signed into law in California, authorizing pharmacists to dispense naloxone without physician or mid level provider prescription, this study finds highly variable participation, availability of naloxone, charge for naloxone, and future interest at 622 pharmacies across various California counties. Unclear if there are trends or further analysis done on participating pharmacies due to lack of access to the full article.
Jensen AN, Beam CM, Douglass AR, Brabson JE, Colvard M, Bean J.
Ment Health Clin. 2019 Jul 1;9(4):294-297. doi: 10.9740/mhc.2019.07.294. eCollection 2019 Jul.
Comments: Describes a video telehealth clinic led by a pharmacist to provide education about overdose and naloxone, intended to reach patients in more rural and difficult to reach areas. Seems to have reached additional people, but it is unclear how effective the education and training were at reducing overdose risk and overdose events.
23) Public perceptions of naloxone use in the outpatient setting.
Smith JO, Malinowski SS, Ballou JM.
Ment Health Clin. 2019 Jul 1;9(4):275-279. doi: 10.9740/mhc.2019.07.275. eCollection 2019 Jul.
Comments: Among a sample of 405 participants who were reimbursed $0.10 for completing a survey through a crowdsourcing marketplace, the majority were aware that an overdose agent exists. However, although 88% of people believed naloxone is beneficial for accidental overdose, 51% still believe that naloxone enables people who misuse opioids. Public education campaigns about naloxone are still relevant to correct misconceptions and address stigma.
24) Keeping Up with Clinical Advances: Opioid Use Disorder.
Patel B, Kosten TR.
CNS Spectr. 2019 Jul 10:1-7. doi: 10.1017/S109285291900110X. [Epub ahead of print]
Comments: Overview of the various medications that treat opioid use disorder, including methadone, buprenorphine, and naltrexone. Clonidine and lofexidine, which are primarily used to manage symptoms of acute withdrawal, are also discussed.
25) Overdose Deaths and Acute Hepatitis Infections among American Indians in North Carolina.
Cox ME, Dzialowy N, Armstrong L, Proescholdbell S.
N C Med J. 2019 Jul-Aug;80(4):197-203. doi: 10.18043/ncm.80.4.197.
Comments: Based on death certificate data, American Indians (AIs) have 1.3 times greater unintentional medication and drug overdose death rates compared to combined population rates in North Carolina, matching the rates of the white population.
26) Factors associated with willingness to wear an electronic overdose detection device.
Ahamad K, Dong H, Johnson C, Hyashi K, DeBeck K, Milloy MJ, Wood E.
Addict Sci Clin Pract. 2019 Jul 3;14(1):23. doi: 10.1186/s13722-019-0153-5.
Comments: About half of a cohort of people who use drugs in Vancouver, Canada, said they would be willing to wear an overdose detection device, which would alert others in the case that they overdosed. Factors associated with willingness are described.
Bech AB, Clausen T, Waal H, Šaltytė Benth J, Skeie I.
BMC Health Serv Res. 2019 Jul 2;19(1):440. doi: 10.1186/s12913-019-4282-z.
Comments: Analysis of crude mortality rate (CMR) and causes of death in Norway’s OAT patient population from January 2014 to December 2015. 1.4% mortality rate among OAT patients in this 2-year period. Deaths were attributed to somatic disease (45%), followed by drug-induced death (42%), and violent death (12%). CMR was higher in men and in patients taking methadone compared with buprenorphine. Results may be somewhat limited by small sample size of deaths in OAT patients (n=200).
Moallef S, Nosova E, Milloy MJ, DeBeck K, Fairbairn N, Wood E, Kerr T, Hayashi K.
Public Health Rep. 2019 Jul/Aug;134(4):423-431. doi: 10.1177/0033354919857084. Epub 2019 Jun 18.
Comments: 93.9% of participants who report drug use in this Vancouver study reported some level of fentanyl risk knowledge. 72.5% of participants (and 60% of opioid users in the sample) perceived their risk of fentanyl overdose as nonexistent or low. Participants who perceived a lower risk were also less likely to report a recent nonfatal overdose, recent injection drug use, and awareness of recent exposure to fentanyl citing never or rarely using opioids as the most common reason. Additional findings show that people who were incarcerated were less likely than those who were not incarcerated to perceive their risk of fentanyl overdose as lower. Results are limited to self-reported data.
29) Monoclonal Antibodies for Combating Synthetic Opioid Intoxication.
Smith LC, Bremer PT, Hwang CS, Zhou B, Ellis B, Hixon MS, Janda KD.
J Am Chem Soc. 2019 Jul 3;141(26):10489-10503. doi: 10.1021/jacs.9b04872. Epub 2019 Jun 25.
Comments: Study about a monoclonal antibody therapy to treat exposure to fentanyl and its analogs. The authors propose this antibody therapy as a potential alternative to naloxone; its half life is much longer and would eliminate the risk of falling back into overdose (which is actually remarkably low…). Ethical issues certainly do come up and there are real logical challenges, with which opioids are targeted, administration, prolonged withdrawal, etc.
Parmar MKB, Strang J, Choo L, Meade AM, Bird SM.
Addiction. 2019 Jul;114(7):1325. doi: 10.1111/add.14284. No abstract available.
Comments: This is clarification of the study results reported in the N-ALIVE trial of NOR (Naloxone-on-Release), which provided naloxone to former heroin users after release from prison. The committee stopped the trial early because only 5/20 of the former inmates who received naloxone on release used it on themselves and 15/20 used it on other people. This was supposed to be the definitive study of naloxone as overdose prevention, but it got beaten by the reality of naloxone as a community medication.
31) Changing Trends in Opioid Overdose Deaths and Prescription Opioid Receipt Among Veterans.
Lin LA, Peltzman T, McCarthy JF, Oliva EM, Trafton JA, Bohnert ASB.
Am J Prev Med. 2019 Jul;57(1):106-110. doi: 10.1016/j.amepre.2019.01.016. Epub 2019 May 22.
Comments: Analysis of opioid categories and receipt of prescription opioids among veterans who died from opioid overdose in the Veteran’s Health Administration. Rates of overdose from synthetic opioids and heroin increased substantially from 2010 to 2016, while prescription opioid receipt within 3 months before death decreased from 54% in 2010 to 26% in 2016. Full text not available.
32) Suspected Heroin Overdoses in US Emergency Departments, 2017-2018.
Vivolo-Kantor AM, Hoots B, David F, Gladden RM.
Am J Public Health. 2019 Jul;109(7):1022-1024. doi: 10.2105/AJPH.2019.305053. Epub 2019 May 16.
Comments: Analysis of suspected heroin overdoses during 2017-2018 in 23 states and jurisdictions funded by the CDC and Prevention Enhanced State Opioid Overdose Surveillance program. Results show 21.5% overall decline in heroin overdose ED visits, but significant increase in Illinois, Indiana and Utah. Limitations of the study include lack of examining other opioids such as fentanyl and limited sensitivity of ED coding.
Morgan JR, Schackman BR, Weinstein ZM, Walley AY, Linas BP.
Drug Alcohol Depend. 2019 Jul 1;200:34-39. doi: 10.1016/j.drugalcdep.2019.02.031. Epub 2019 May 3.
Comments: The Massachusetts database allows for extraordinary analyses. This one demonstrated, in a cohort of 43,846 people, that individuals receiving buprenorphine therapy following an opioid use disorder diagnosis were at a lower risk of opioid overdose (hazard ratio 0.40 [0.35-0.46]), whereas a significant risk reduction or association was not observed for naltrexone (oral [hazard ratio 0.93 {0.71-1.22}] or extended-release injectable [hazard ratio 0.74 {0.42-1.31}]). The naltrexone category is underpowered here, but does not appear likely to achieve the benefits of buprenorphine.
34) Why aren’t Australian pharmacists supplying naloxone? Findings from a qualitative study.
Olsen A, Lawton B, Dwyer R, Taing MW, Chun KLJ, Hollingworth S, Nielsen S.
Int J Drug Policy. 2019 Jul;69:46-52. doi: 10.1016/j.drugpo.2019.03.020. Epub 2019 May 9.
Comments: In Australia, over-the-counter naloxone dispensing by pharmacists is happening, though still very under-utilized. Strategies to improve pharmacist uptake are at individual (training) and system (regulation, supply) levels.
35) Evaluation of a lateral flow immunoassay for the detection of the synthetic opioid fentanyl.
Angelini DJ, Biggs TD, Maughan MN, Feasel MG, Sisco E, Sekowski JW.
Forensic Sci Int. 2019 Jul;300:75-81. doi: 10.1016/j.forsciint.2019.04.019. Epub 2019 Apr 26.
Full text not available. There remains a huge fear of fentanyl among many first responders, irresponsibly promoted in this abstract. Fentanyl and its analogues don’t absorb well through skin. In general, to get sufficient exposure, one would have to essentially bathe in fentanyl. The cases of purported exposure commonly involve panic attacks or, in some subsequently documented circumstances, surreptitious ingestion of the drugs that were found at the scene. This fear leads to stigma against people who use drugs, dangerous legislation, and abandonment of patients in need.
36) Editorial: Prescription for Addiction.
Riggs P.
J Am Acad Child Adolesc Psychiatry. 2019 Jul;58(7):659-660. doi: 10.1016/j.jaac.2019.03.030. Epub 2019 Apr 17.
The editorial calls attention to the gap in knowledge of predictive risk factors for drug use in youth, which limits the ability to develop effective interventions. Full text not available.
Krieter P, Chiang CN, Gyaw S, Skolnick P, Snyder R.
Drug Metab Dispos. 2019 Jul;47(7):690-698. doi: 10.1124/dmd.118.085977. Epub 2019 Apr 16.
Comments: I’m really not clear on why we need longer acting opioid overdose reversal agents. There are rare circumstnaces where this is desirable, but that is really uncommon. Most of the time people don’t want to be in a prolonged withdrawal. Use of buprenorphine after naloxone has been done and can be effective. This is a weird research pathway.
Donaghy J.
Evid Based Nurs. 2019 Jul;22(3):77. doi: 10.1136/ebnurs-2019-103072. Epub 2019 Mar 21. No abstract available.
Reflections of opioid users who have used take home naloxone on others when overdosing. Full text or abstract not available.
39) No end to the crisis without an end to the waiver.
Frank JW, Wakeman SE, Gordon AJ.
Subst Abus. 2018;39(3):263-265. doi: 10.1080/08897077.2018.1543382. No abstract available.
Requiring a waiver to prescribe the most important medication to treat opioid use disorder is really messed up, especially since so many of these patients were provided the opioids that got them hooked by providers who didn’t need a waiver to prescribe those medications. Backwards and archaic.
40) Novel Formulations of Buprenorphine for Treatment of Opioid Use Disorder.
Rosenthal RN.
Focus (Am Psychiatr Publ). 2019 Apr;17(2):104-109. doi: 10.1176/appi.focus.20180043. Epub 2019 Apr 10.
Comments: The study aims to find novel delivery systems to improve outcomes of intermediate and long acting exposure to buprenorphine. Novel formulations are helpful to ensure buprenorphine access in circumstances that limit adherence, as well as where daily dose formulations may be perceived as problematic (such as correctional settings).