We start out 2019 with 42 new papers. The overarching theme is fentanyl – with some useful data really starting to emerge. Also several addressing surveillance-type issues, which is still badly needed and exciting work. We’ve also got the standard naloxone papers and a few weird drugs (e.g. tramadol and kratom).
1) Drugs Most Frequently Involved in Drug Overdose Deaths: United States, 2011-2016.
Hedegaard H, Bastian BA, Trinidad JP, Spencer M, Warner M.
Natl Vital Stat Rep. 2018 Dec;67(9):1-14.
Comment: Nice summary of the data demonstrating the shift from prescribed opioids to heroin to fentanyl, with rising methamphetamine and persistent cocaine presence.
Krieter P, Gyaw S, Chiang CN, Crystal R, Skolnick P.
J Clin Pharmacol. 2019 Jan 30. doi: 10.1002/jcph.1384. [Epub ahead of print]
Comment: Fascinating that the half-life of naltrexone is only 2.2 hours when administered intranasally … would be great to see that for managing alcohol use.
3) Emergency department physicians’ and pharmacists’ perspectives on take-home naloxone.
Holland TJ, Penm J, Dinh M, Aran S, Chaar B.
Drug Alcohol Rev. 2019 Jan 29. doi: 10.1111/dar.12894. [Epub ahead of print]
Comment: Qualitative assessment of opinions.
4) Take-home naloxone: a life saver in opioid overdose.
The Lancet.
Lancet. 2019 Jan 26;393(10169):296. doi: 10.1016/S0140-6736(19)30153-9. No abstract available.
Comment: Editorial supporting take-home naloxone.
Goodman D, Zagaria AB, Flanagan V, Deselle FS, Hitchings AR, Maloney R, Small TA, Vergo AV, Bruce ML.
J Midwifery Womens Health. 2019 Jan;64(1):104-111. doi: 10.1111/jmwh.12943.
Comment: Some good changes – more naloxone provided, more counseling regarding breastfeeding, and more nicotine-replacement therapy initiated.
Karamouzian M, Kuo M, Crabtree A, Buxton JA.
Int J Drug Policy. 2019 Jan 25. pii: S0955-3959(19)30014-3. doi: 10.1016/j.drugpo.2019.01.006. [Epub ahead of print]
Comment: Great analysis of naloxone programmatic data. 55.7% of lay naloxone administrations were followed by a call for emergency medical services, again demonstrating that we do not have data showing a reduction in calling 911 when naloxone is administered.
Murray BP, Carpenter JE, Dunkley CA, Moran TP, Alfaifi M, Alsukaiti WS, Kazzi Z.
Clin Toxicol (Phila). 2019 Jan 24:1-5. doi: 10.1080/15563650.2018.1547826. [Epub ahead of print]
Comment: Tramadol is a weird drug. This analysis found that when it caused an opioid-like overdose, seizures were less likely, and that naloxone use was not associate with tramadol seizures.
McLean K, Monnat SM, Rigg K, Sterner GE 3rd, Verdery A.
Subst Use Misuse. 2019 Jan 24:1-12. doi: 10.1080/10826084.2018.1552303. [Epub ahead of print]
Comment: Fentanyl use patterns are evolving – it seems to be here to stay this time.
9) Development of a Cascade of Care for responding to the opioid epidemic.
Williams AR, Nunes EV, Bisaga A, Levin FR, Olfson M.
Am J Drug Alcohol Abuse. 2019 Jan 24:1-10. doi: 10.1080/00952990.2018.1546862. [Epub ahead of print]
Comment: Nice to see this development.
10) Blockade of the human ether a-go-go related gene (hERG) potassium channel by fentanyl.
Tschirhart JN, Li W, Guo J, Zhang S.
Mol Pharmacol. 2019 Jan 21. pii: mol.118.114751. doi: 10.1124/mol.118.114751. [Epub ahead of print]
Comment: First, you gotta love the naming culture for these genes. Now the human ether a-go-go gene potassium channel effects could prolong the QT interval, which could result in ventricular arrhythmias and, ultimately, cardiac arrest. Is this playing a role in fentanyl-related deaths? Not sure.
Notta D, Black B, Chu T, Joe R, Lysyshyn M.
Drug Alcohol Depend. 2019 Jan 15;196:46-50. doi: 10.1016/j.drugalcdep.2018.12.016. [Epub ahead of print]
Comment: Great use of these data. As fentanyl entered the heroin supply in Vancouver, the rate of “heroin” overdoses rose 4.8 fold. This is interesting, as fentanyl knowingly used at the Sydney injection facility was 4 times more likely than heroin to result in overdose – honestly I would have expected an even more substantial increase in “heroin” overdose events in the context of heroin contaminated with fentanyl. Notably, there was a several fold increase in overdose events for all drugs being injected in Vancouver over the period studied. They also saw an increase in rigidity (a potential complication of fentanyl) from 10.4% of “heroin” overdoses in 2010/11 to 18.9% in 2017.
Prangnell A, Fairgrieve C, Nosova E, DeBeck K, Milloy MJ, Hayashi K.
Subst Use Misuse. 2019 Jan 20:1-6. doi: 10.1080/10826084.2018.1555257. [Epub ahead of print]
Comment: Two-thirds of people who overdosed believed their drugs had been adulterated. While the current drug supply is very dynamic, I suspect this finding would hold for overdoses in areas not heavily affected by fentanyl; that is, this is a common perception among people who have overdosed, explained by the actor-observer bias.
Alexandridis AA, Dasgupta N, McCort AD, Ringwalt CL, Rosamond WD, Chelminski PR, Marshall SW.
Inj Epidemiol. 2019 Jan 21;6(1):2. doi: 10.1186/s40621-018-0179-2.
Comment: Limited effects.
14) What should clinicians do as fentanyl replaces heroin?
Bisaga A.
Addiction. 2019 Jan 20. doi: 10.1111/add.14522. [Epub ahead of print] No abstract available.
Comment: Be creative, be innovative, don’t be shy.
Delargy I, Crowley D, Van Hout MC.
Harm Reduct J. 2019 Jan 17;16(1):5. doi: 10.1186/s12954-018-0272-4. Review.
Comment: 20 years and 10,000 patients later.
16) Overdose Deaths Involving Fentanyl and Fentanyl Analogs – New York City, 2000-2017.
Colon-Berezin C, Nolan ML, Blachman-Forshay J, Paone D.
MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):37-40. doi: 10.15585/mmwr.mm6802a3.
Comment: It’s always tricky to use toxicology results in overdose mortality surveillance because there are many substances found on toxicology which may not have contributed to the death (e.g. something the patient takes medically that was at a low or appropriately therapeutic level and doesn’t interact with likely causal drugs, or something that is a by-product of decomposition). In this circumstance, however, it made sense.
Saloner B, Levin J, Chang HY, Jones C, Alexander GC.
JAMA Netw Open. 2018 Aug 3;1(4):e181588. doi: 10.1001/jamanetworkopen.2018.1588.
Comment: Buprenorphine treatment increased and opioid pain reliever prescriptions did not. That makes solid sense.
Skulberg AK, Åsberg A, Khiabani HZ, Røstad H, Tylleskar I, Dale O.
Addiction. 2019 Jan 14. doi: 10.1111/add.14552. [Epub ahead of print]
Comment: Intranasal 1.4mg was ~50% bioavailable, which is half as good as intramuscular, and the pharmacokinetics were similar to 0.8mg intramuscular, although the time to peak effect was about 5 minutes slower.
Handanagic S, Bozicevic I, Sekerija M, Rutherford GW, Begovac J.
Int J Drug Policy. 2019 Jan 11;64:95-102. doi: 10.1016/j.drugpo.2018.11.017. [Epub ahead of print]
Comment: Polydrug injection.
20) Increased Presence of Fentanyl in Cocaine-Involved Fatal Overdoses: Implications for Prevention.
Nolan ML, Shamasunder S, Colon-Berezin C, Kunins HV, Paone D.
J Urban Health. 2019 Jan 11. doi: 10.1007/s11524-018-00343-z. [Epub ahead of print]
Comment: These data suggest that fentanyl is responsible for a good amount of the increase in cocaine deaths in NYC. Was that intentionally consumed or contaminating cocaine? Given that the demographics of cocaine related deaths have historically been fairly distinct from opioid deaths in NYC, I wonder if comparing demographics would help to elucidate which is the case.
21) Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health.
Lovrecic B, Lovrecic M, Gabrovec B, Carli M, Pacini M, Maremmani AGI, Maremmani I.
Int J Environ Res Public Health. 2019 Jan 9;16(2). pii: E177. doi: 10.3390/ijerph16020177. Review.
Comment: Yup, we’re in a mess.
22) Primary Care for Persons Who Inject Drugs.
Visconti AJ, Sell J, Greenblatt AD.
Am Fam Physician. 2019 Jan 15;99(2):109-116.
Comment: Love this topic, which drove me into medicine in the first place. Excellent to see physicians, scientists, and academic publications take on this need.
23) Reversal of Pediatric Opioid Toxicity with Take-Home Naloxone: a Case Report.
Lebin JA, Chen BC, Valento MJ.
J Med Toxicol. 2019 Jan 10. doi: 10.1007/s13181-018-0695-z. [Epub ahead of print]
Comment: This may be the first journal report of pediatric reversal with take-home naloxone, but it’s not the first story … it’s been happening in the community for decades.
24) Drug Overdose Deaths Among Women Aged 30-64 Years – United States, 1999-2017.
VanHouten JP, Rudd RA, Ballesteros MF, Mack KA.
MMWR Morb Mortal Wkly Rep. 2019 Jan 11;68(1):1-5. doi: 10.15585/mmwr.mm6801a1.
Comment: Increased overdose mortality across the board among women.
25) Increasing Naloxone Access and Use to Prevent Opioid Overdose Death and Disability.
White ND.
Am J Lifestyle Med. 2018 Oct 20;13(1):33-35. doi: 10.1177/1559827618803874. eCollection 2019 Jan-Feb. Review.
Comment: Legislation and pronouncements have only done so much.
26) Opioid overdose detection using smartphones.
Nandakumar R, Gollakota S, Sunshine JE.
Sci Transl Med. 2019 Jan 9;11(474). pii: eaau8914. doi: 10.1126/scitranslmed.aau8914.
Comment: This is a fascinating topic. We can saturate the world with naloxone, but it still won’t prevent overdose events from becoming fatal among people who are isolated from others (e.g. marginally housed, living in hotel rooms). In San Francisco, about one-third of deaths occurred in single-room occupancy hotel units – a number that is unlikely to be significantly affected by responder interventions. To have non-invasive tools that can detect concerning vital signs could be hugely beneficial if implemented well.
Lugoboni F, Zamboni L, Cibin M, Tamburin S; Gruppo InterSERT di Collaborazione Scientifica (GICS).
Eur Addict Res. 2019;25(1):10-19. doi: 10.1159/000496112. Epub 2019 Jan 9.
Comment: People who inject drugs frequently try to inject other drugs.
Atighi Y, Eizadi-Mood N, Mansourian M, Zamani A, Saffaei A, Sabzghabaee AM.
J Res Pharm Pract. 2018 Oct-Dec;7(4):200-204. doi: 10.4103/jrpp.JRPP_16_141.
Comment: Accidental opioid poisoning amoung children at home is always tragic. While our first effort has to be avoiding such events, an earlier manuscript today showed that having naloxone at home can help mitigate when they do occur.
Goldman JE, Waye KM, Periera KA, Krieger MS, Yedinak JL, Marshall BDL.
Harm Reduct J. 2019 Jan 8;16(1):3. doi: 10.1186/s12954-018-0276-0.
Comment: People use them and often implement some overdose prevention or management strategies when results are positive.
30) Legally Lethal Kratom: A Herbal Supplement with Overdose Potential.
Palasamudram Shekar S, Rojas EE, D’Angelo CC, Gillenwater SR, Martinez Galvis NP.
J Psychoactive Drugs. 2019 Jan 8:1-3. doi: 10.1080/02791072.2018.1562591. [Epub ahead of print]
Comment: Kratom’s another “weird” drug with some opioid properties. Took 10 days to recover – wow!
31) The importance of buprenorphine research in the opioid crisis.
Pendergrass SA, Crist RC, Jones LK, Hoch JR, Berrettini WH.
Mol Psychiatry. 2019 Jan 7. doi: 10.1038/s41380-018-0329-5. [Epub ahead of print]
Comment: Yep. Although I’d say implementation is more important.
32) Implementation of a collaborative model for opioid overdose prevention on campus.
Hill LG, Holleran Steiker LK, Mazin L, Kinzly ML.
J Am Coll Health. 2019 Jan 7:1-4. doi: 10.1080/07448481.2018.1549049. [Epub ahead of print]
Comment: Further expansion of naloxone.
33) Divergence In Recent Trends In Deaths From Intentional And Unintentional Poisoning.
Hempstead K, Phillips J.
Health Aff (Millwood). 2019 Jan;38(1):29-35. doi: 10.1377/hlthaff.2018.05186.
Comment: Notwithstanding a huge increase in unintentional opioid deaths and a shift in the causal opioids, poisoning suicide deaths have not changed during this period, again suggesting that suicide and unintentional overdose are distinct processes.
34) Medication Treatment For Opioid Use Disorders In Substance Use Treatment Facilities.
Mojtabai R, Mauro C, Wall MM, Barry CL, Olfson M.
Health Aff (Millwood). 2019 Jan;38(1):14-23. doi: 10.1377/hlthaff.2018.05162.
Comment: Uh … yeah. Please.
Eukel HN, Skoy E, Werremeyer A, Burck S, Strand M.
J Contin Educ Health Prof. 2019 Jan 3. doi: 10.1097/CEH.0000000000000233. [Epub ahead of print]
Comment: More training pharmacists.
36) Commentary on Stam et al. (2019): Drugs, death and statistics.
Darke S.
Addiction. 2019 Jan 6. doi: 10.1111/add.14520. [Epub ahead of print] No abstract available.
Comment: As usual, the author has insightful comments on overdose research and surveillance. Heroin deaths are often miscoded as morphine (or codeine?) deaths and stimulant deaths are often missed because the immediate medical cause of a cerebral hemorrhage or cardiac arrest is sufficient for the cause of death field.
Gerace E, Seganti F, Luciano C, Lombardo T, Di Corcia D, Teifel H, Vincenti M, Salomone A.
Drug Alcohol Rev. 2019 Jan;38(1):50-56. doi: 10.1111/dar.12887. Epub 2019 Jan 6.
Comment: Portable drug detection is very exciting.
Cheng T, Small W, Dong H, Nosova E, Hayashi K, DeBeck K.
Subst Abuse Treat Prev Policy. 2018 Nov 27;13(1):41. doi: 10.1186/s13011-018-0180-3.
Comment: No age differences.
39) Utilizing Buprenorphine in the Emergency Department after Overdose.
Johns SE, Bowman M, Moeller FG.
Trends Pharmacol Sci. 2018 Dec;39(12):998-1000. doi: 10.1016/j.tips.2018.10.002. Review.
Comment: Good idea, when patients want it.
40) Pharmacological Research as a Key Component in Mitigating the Opioid Overdose Crisis.
Baumann MH, Kopajtic TA, Madras BK.
Trends Pharmacol Sci. 2018 Dec;39(12):995-998. doi: 10.1016/j.tips.2018.09.006. Review.
Comment: Review with focus on what new medications could provide.
41) At-a-glance – What can paramedic data tell us about the opioid crisis in Canada?
Do MT, Furlong G, Rietschlin M, Leyenaar M, Nolan M, Poirier P, Field B, Thompson W.
Health Promot Chronic Dis Prev Can. 2018 Sep;38(9):339-342. doi: 10.24095/hpcdp.38.9.06. English, French.
Comment: It’s tricky to track opioid overdose with paramedic calls for several reasons (e.g. diagnosis codes are preliminary in this triage service, using naloxone administration as a marker misses a lot of events that aren’t “typical” heroin overdoses, the impact of naloxone programming is unclear, etc). Nonetheless, if you can access the data in a useful way, exploring this data source is irresistible.
Saucier R, Wolfe D, Dasgupta N.
Drug Saf. 2018 Oct;41(10):981-988. doi: 10.1007/s40264-018-0653-3. Erratum in: Drug Saf. 2018 May 24.
Comment: It is concerning that in overdose deaths the manufacturer placed the blame on opioid use disorder and did not consider elevated risk for overdose after treatment discontinuation. I would agree that a registry is in order.