Monday, September 10, 2012

PubMed Update: A Year in Overdose

Here is a summary of our first year of PubMed updates. This list is NOT comprehensive and focuses on opioids at the expense of stimulant issues. There are some excellent papers not listed in the PubMed database (e.g. a couple of great papers out of Scotland we’ve discussed here and many conference abstracts).

So … there were an impressive 81 papers! Basic epidemiology and opioid analgesics dominate, but the list is quite diverse. I’ve roughly categorized papers, but many would fit into multiple categories, and I have not updated the comments …


1) Drug overdose deaths --- Florida, 2003-2009
Centers for Disease Control and Prevention
MMWR Morb Mortal Wkly Rep. 2011 Jul 8; 60(26):869-72
Comments: Again, oxycodone has arisen as a major source of overdose mortality. The use characteristics that lead to mortality, however, remain unexplained.

Bohnert AS, Tracy M, Galea S. Drug Alcohol Depend. 2011 Aug 10.
Comment: Another analysis from a non-fatal overdose survey in Harlem and the South Bronx. There have been some concerning results in terms of witness management of overdose from this study. We know that those who have overdosed are at higher risk of overdose and from a 2005 analysis also know that they are less likely to contact emergency medical services when they witness an overdose. Now we know that these findings apply to those who witness multiple overdoses as well (they appear to be almost the same population). Authors propose that prior negative experiences with medical service might dissuade contact at future overdoses, although perhaps successful prior lay resuscitation efforts also discourage calling for help.

Leach D, Oliver P. Curr Drug Abuse Rev. 2011 Aug 12. [Epub ahead of print]
Comment: I don’t have access to the full article and hope that naloxone distribution is discussed as one of the options.

Hser Y, Kagihara J, Huang D, Evans E, Messina N. Addiction. 2011 Aug 10
Comment: Mortality among pregnant or parenting women seeking substance abuse treatment (including heroin, cocaine, alcohol, marijuana, and methamphetamine) over ten years was 8.4x higher than the general population, the largest portion of which was from overdose (29%). The authors do not breakdown overdose by primary drug problem (i.e. can’t tell if most of the overdoses were among heroin users or if they were more evenly distributed).

Webster LR, Cochella S, Dasgupta N, Fakata KL, Fine PG, Fishman SM, Grey T, Johnson EM, Lee LK, Passik SD, Peppin J, Porucznik CA, Ray A, Schnoll SH, Stieg RL, Wakeland W.
Pain Med. 2011 Jun;12 Suppl 2:S26-35.
Comment: A review of structural and individual factors related to opioid overdose increases in the U.S.

Marasovic Susnjara I, Definis Gojanovic M, Vodopija D, Capkun V, Smoljanovic A.
Croat Med J. 2011 Oct 15;52(5):629-36.
Comment: Authors developed an interesting association of war and post-war periods with increased overdose deaths, the majority of which were due to heroin and half of which involved multiple drugs. Authors hypothesize that the reason for this increase is due to social instability and increased drug supply.

Evans JL, Tsui JI, Hahn JA, Davidson PJ, Lum PJ, Page K.
Am J Epidemiol. 2012 Jan 6.
Comment: Thought I'd start with the best one this time, an excellent and desperately needed analysis that includes some estimates on mortality rates in one of the few prospective cohorts left.

Green TC, McGowan SK, Yokell MA, Pouget ER, Rich JD.
AIDS. 2011 Nov 22.
Comment: In many areas of the world, overdose is the most common cause of death among those at risk for (or infected with) HIV. This study found that HIV-seropositivity was associated with a 74% increased risk overdose death (I can't access the article to provide more detail about this).

Fellows-Smith J.
J Opioid Manag. 2011 Nov-Dec;7(6):443-9.
Comment: The importance of this article is not reflected in the title. This is a data linkage study in Australia looking at mortality rates among those receiving methadone (0.7%) versus naltrexone (2.6%) for opioid therapy. Again this raises the major concerns about opioid overdose after naltrexone therapy, concerns that were clearly inadequately addressed prior to FDA approval of naltrexone for opioid dependence.

Rosca P, Haklai Z, Goldberger N, Zohar P, Margolis A, Ponizovsky AM.
Drug Alcohol Depend. 2012 Apr 6. [Epub ahead of print]
Comment: Rate of overdose mortality was 0.22/100 person-years (i.e. 0.22%), one-quarter to one-fifth the expected rate in most studies of other cohorts

Gibson A, Randall D, Degenhardt L.Addiction. 2011 Dec;106(12):2186-92. doi: 10.1111/j.1360-0443.2011.03575.x. Epub 2011 Oct 17.
Comment: This paper discusses another major interest of mine - hepatitis C. Hep C-related deaths have doubled since I began medical practice and will double again over the next 10-15 years. Broadened screening and improved access to treatment are desperately needed and will more than double the impact of the improved treatments we are already seeing.

Lin C, Detels R.
Drug Alcohol Depend. 2011 Aug 1;117(1):45-9. Epub 2011 Feb 9.
Comment: Interesting discussion of problems with methadone dosing in China.

Susnjara IM, Smoljanović A, Gojanović MD.
Coll Antropol. 2011 Sep;35(3):823-8.
Comment: Basic epidemiology of overdose deaths in Croatia that again emphasizes the role of polydrug use.

Vento AE, Schifano F, Corkery JM, Pompili M, Innamorati M, Girardi P, Ghodse H.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Jul 1;35(5):1279-83.
Comment: Can't access full article and I'm unclear how the results tie to conclusions from the abstract.

Whelan PJ, Remski K.
J Neurosci Rural Pract. 2012 Jan;3(1):45-50.
Comment: Includes a brief review of the lower overdose risk with buprenorphine.

Andrews JY, Kinner SA.
BMC Public Health. 2012 Apr 4;12(1):270. [Epub ahead of print]
Comment: An interesting exploration of circumstances surrounding prisoner death post-release.

Kinner SA, Milloy MJ, Wood E, Qi J, Zhang R, Kerr T.
Addict Behav. 2012 Feb 7. [Epub ahead of print]
Comment: Prior overdose, daily or binge drug use, and public injecting are associated with nonfatal overdose among recently released drug users.

Wilcher G.
Am J Forensic Med Pathol. 2011 Dec;32(4):314-8.
Comment: Intriguing review of 5 cases of drug-induced death among "body packers" or "body stuffers", including a review of that language. Interestingly, most of the deaths were due to overdose on consumed drugs rather than toxicity from rupture of drug packets.

Shah NG, Lathrop SL, Flores JE, Landen MG.
Drug Alcohol Depend. 2012 Apr 16.
Comment: An analysis of New Mexico overdose deaths (many of us have been waiting with bated breath for a deeper analysis of deaths there). Authors found that living in a border region was associated with less overdose death, particularly from heroin or methadone; among their hypotheses is that this is a paradoxical benefit of reduced access to medical care and opioid prescriptions. 

Jovanović T, Lazarević D, Nikolić G.
Vojnosanit Pregl. 2012 Apr;69(4):326-32. Serbian.
Comment: Does anyone read Serbian? I'd love to see some additional comment on this intriguing paper. The issues around depot naltrexone versus agonist maintenance are becoming a real issue. The concerns around overdose death in the setting of naltrexone have not been adequately addressed. This paper appears to compare depression scales for patients on those two therapies, but I can't tell from the abstract exactly what the populations are or what the analysis showed.

Garfein RS, Rondinelli A,Barnes RF, Cuevas J, Metzner M, Velasquez M, Rodriguez D, Reilly M, Xing J,Teshale EH.
J Urban Health. 2012 Jul 6.[Epub ahead of print]
Comment: Focusing on the overdose component of the manuscript: Dr Garfein and colleagues found a relatively low rate of lifetime overdose in this cohort of 18-40 year olds of 28.1% (an analysis of these data with overdose as the outcome is clearly warranted). Most notably, they found an independent association of history of overdose with HCV infection. 
  This is consistent with other recent data suggesting an association between overdose and other drug-related risk behaviors such as syringe sharing. A poster this month at the International AIDS Conference shows that those who administer naloxone at their most recent witnessed overdose are less likely to share syringes than those who didn't administer naloxone. Moreover, the reductions in overdose we have seen in regions with well-funded naloxone distribution programs have been far more impressive than mathematical modeling would suggest. All together, these data force me to wonder if naloxone distribution has an effect well in excess of its ability to reverse an overdose.

McNeely J, Gourevitch MN, Paone D, Shah S, Wright S, Heller D.
BMC Public Health. 2012 Jun 18;12(1):443. [Epub ahead of print]
Comment: An excellent team of authors has attempted the perhaps impossible task of estimating the number of opioid users in New York City - a task that was hard enough with heroin alone. The results seem consistent enough to what would be predicted by large-scale epidemiologic studies to be of substantial use in future. I've asked for additional thoughts on this approach and will post comments when they come.

Harris JL, Lorvick J, Wenger L, Wilkins T, Iguchi MY, Bourgois P, Kral AH.
J Urban Health. 2012 Jun 12. [Epub ahead of print]
Comment: Among "low frequency" heroin users (who used 1-10 times in the past 30 days) 7.0% had overdosed in the past year. Among "high frequency" heroin users, 14.8% had overdosed in the past year. So infrequent heroin injectors overdose less in this sample. The low frequency injectors were marginally older, which may partially explain less overdose (that is, users who survive to older ages are less likely to overdose in a given year), yet I am still somewhat surprised by this result as I would presume low frequency injectors would have low or inconsistent opioid tolerance that might raise their risk of overdose. At this time, we clearly can't consider bouts of abstinence as a behavioral risk factor for overdose.

Maxwell JC, Coleman JJ, Feng SY, Goto CS, Tirado CF.
Drug Alcohol Depend. 2012 Jul 3. [Epub ahead of print]
Comment: A mixture of heroin, Benadryl, and APAP (basically tylenol) - this is an intriguing report of the use of "cheese" heroin in Dallas, Texas, with an appropriate attention to overdose. As authors experienced, overdose data are limited and disappointing given the severity of that consequence.

Dasgupta N, Davis J, Jonsson Funk M, Dart R.
PLoS One. 2012;7(7):e41181. Epub 2012 Jul 19.
Comment: Intriguing analysis of calls to poison control centers. The number of methadone calls was associated with overall methadone mortality, although the calls tended to be from younger, and more often female, individuals that may not have required medical attention. How about a state-by-state breakdown of Google Methadone Trends?

Kinner SA, Milloy MJ, Wood E, Qi J, Zhang R, Kerr T.
Addict Behav. 2012 Jun;37(6):691-6. Epub 2012 Feb 7.
Comment: More great data from Vancouver! Large cohort (N=2,515) of drug users; one-third had a non-fatal overdose in the past 6 months. Overdose was associated with more frequent use and more polydrug use. Older age was protective, which is interesting and supports the emerging concept that some drug users overdose … and some do not. Their findings around HIV and overdose risk are difficult to interpret and frankly require further evaluation. Those recently incarcerated were about twice as likely to report recent overdose.

28) Mortality risk in a cohort of subjects reported by authorities for cannabis possession for personal use. Results of a longitudinal study.
Pavarin RM, Berardi D.
Epidemiol Prev. 2011 Mar-Apr;35(2):89-93.
Comment: A database-linkage study of people arrested for marijuana possession in Bologna from 1990-2004. I'm unable to access the full article, but the abstract reports a standardized mortality ratio (sort of like an odds ratio) for those who ultimately sought public drug treatment of 15 and those who didn't seek public treatment of 2. Overdose was a leading cause of death for both groups.

Britton PC, Bohnert AS, Wines JD Jr, Conner KR.
Addict Behav. 2011 Sep 2.
Comment: The intentionality of overdose is a recurrent issue. I read this article and frankly do not understand what the authors did.


1) Sudden Bilateral Sensorineural Hearing Loss following Polysubstance Narcotic Overdose.
Schweitzer VG, Darrat I, Stach BA, Gray E.
J Am Acad Audiol. 2011 Apr;22(4):208-14.
Comment: A report of hearing loss after a poly-drug binge (heroin, benzos, alcohol, and crack). Again, I'm unable to access the full article. However, this has been reported before in relation to some opioids and the mechanism remains unclear.

Todorović MS, Mitrović S, Aleksandrić B, Mladjenović N, Matejić S.
Vojnosanit Pregl. 2011 Aug;68(8):639-42.
Comment: This is a really interesting paper out of Serbia. Pulmonary edema (water in the lungs) by far most common pathological finding in drug users who died suddenly, most of whom were opioid users. This makes sense and is not inconsistent with the known mechanism of death from opioids. Of note, pulmonary edema has been reported in people who were administered naloxone, but this is almost certainly due to the overdose itself rather than any toxicity from naloxone.

Upadhyay SP, Mallick PN, Elmatite WM, Jagia M, Taqi S.
Indian J Palliat Care. 2011 Sep;17(3):251-4.
Comment: An interesting use of a particular sedative to assist with opioid withdrawal in an intensive care unit.

Fernández P, Seoane S, Vázquez C, Tabernero MJ, Carro AM, Lorenzo RA.
J Appl Toxicol. 2012 Feb 15. doi: 10.1002/jat.2722. [Epub ahead of print]
Comment: An interesting method for identifying several drugs of abuse simoultaneously.

Dinis-Oliveira RJ, Santos A, Magalhães T.
Toxicol Mech Methods. 2012 Feb;22(2):159-60.
Comment: I'm not able to access. Anyone?

Soravisut N, Rattanasalee P, Junkuy A, Thampitak S, Sribanditmongkol P.
J Med Assoc Thai. 2011 Dec;94(12):1540-6.
Comment: There's an error in this title - it should be opiate versus non-opiate overdose deaths. Basic epidemiology.

Shaw KA, Babu KM, Hack JB.
J Emerg Med. 2011 Dec;41(6):635-9. Epub 2010 Dec 9.
Comment: An unusual toxicity to opioid overdose, but one that has been previously documented. Generally neurologic in origin and reversible with removal of the offending opioid agent.

Carroll I, Heritier Barras AC, Dirren E, Burkhard PR, Horvath J.
Clin Neurol Neurosurg. 2012 Feb 16. [Epub ahead of print] No abstract available.
Comment: The precipitating event in this case is a hypoxic event in a patient with an enzyme deficiency, not a direct opioid or benzodiazepine toxicity.
Liu SS, Kovell LC, Horne A Jr, Chang D, Petronis JD, Zakaria S.
J Intensive Care Med. 2012 Apr 29.
Comment: This patient overdosed on opioids and wasn't breathing. After no response to naloxone she was intubated and eventually recovered. It appears that the right ventricle of her heart stopped working for a while due to hypoxia. This should serve as a reminder that medical intervention is often needed in overdose, particularly if the overdose isn't addressed quickly.

Soravisut N, Rattanasalee P, Junkuy A, Thampitak S, Sribanditmongkol P.
J Med Assoc Thai. 2011 Dec;94(12):1540-6.
Comment: An interesting analysis of medical examiner cases in Chiang Mai. Interesting that tourists represented a growing proportion of cases over time.

Hassanian-Moghaddam H, Farajidana H, Sarjami S, Owliaey H.
Am J Emerg Med. 2012 Jul 16. [Epub ahead of print]
Comment: Tramadol is an opioid-like drug that has been involved in some overdose events. The risks for a tramadol overdose are poorly understood. I’m not sure how much this paper adds.

Angst MS, Lazzeroni LC, Phillips NG, Drover DR, Tingle M, Ray A, Swan GE, Clark JD.
Anesthesiology. 2012 Jul;117(1):22-37.
Comment: This is a twin study to look at the genetic contribution to opioid effects. I would recommend perusing the full article (which may be available here) if you work with opioid users, as the results are really intriguing. Directly relevant to overdose is the finding that 30% of the respiratory depression effect is genetic. Furthermore, respiratory depression increases with age (that is, older opioid users tolerate higher CO2 concentrations), more so among men.


Nielsen S, Bruno R, Lintzeris N, Fischer J, Carruthers S, Stoové M.
Drug Alcohol Rev. 2011 May;30(3):291-299.
Comment: This review of individuals seeking treatment in Australia found that, compared to heroin users, prescription opioid users were roughly 10% less likely to report a history of overdose and over twice as likely to report initial use for pain control. Demographics, overall health, and history of injection drug use (IDU) were similar for the two groups. The authors admit that the treatment system is oriented toward IDUs which might explain the similarity of these two groups and limits generalizability. Notably, this to determine the relative risk of overdose among prescription opioid users compared to heroin users.

Maxwell JC.
Drug Alcohol Rev. 2011 May;30(3):264-70.
Comment: This appears to be a thorough and thoughtful review for anyone interested in the issues around prescription opioid abuse in the United States (I can’t access the full article at this time). Data sources include patient surveys, emergency department visits, and mortality and toxicology. Clinical and policy responses are also discussed, including clinician training, risk assessments, treatment agreements, prescription drug monitoring programs, and options for disposal of leftover medication. The author notes the concern that responses could raise many barriers to appropriate pain treatment and yet fail to decrease abuse.

Roxburgh A, Bruno R, Larance B, Burns L.
Med J Aust. 2011 Sep 5;195(5):280-4.
Comment: Oxycodone is becoming an issue in Australia, although not nearly as substantial as in the U.S.

4) Vital signs: overdoses of prescription opioid pain relievers --- United States, 1999--2008
MMWR Morb Mortal Wkly Rep. 2011 Nov 4;60:1487-92.
Comment: This report summarizes the impressive outbreak of death from opioid analgesics (around 15,000 in 2008) in the United States - providing a helpful state-by-state breakdown.

Kahan M, Wilson L, Mailis-Gagnon A, Srivastava A.
Can Fam Physician. 2011 Nov;57(11):1269-76.
Comment: Title is really self-explanatory - recommendations for managing opioids in adolescents.

Barkin RL, Barkin SJ, Irving GA, Gordon A.
Postgrad Med. 2011 Sep;123(5):143-54. Review.
Comment: Another review for physicians of how to not rely so much on opioids for chronic pain.

Weimer MB, Korthuis PT, Behonick GS, Wunsch MJ.
J Addict Med. 2011 Sep;5(3):188-202.
Comment: Interesting data suggesting that two-thirds of methadone-related fatalities were from diverted drug (i.e. not prescribed to the person who died); 28% were prescribed methadone for analgesia. I can't access the full article, but regardless this suggests very few were agonist maintenance patients.

8) A History of Being Prescribed Controlled Substances and Risk of Drug Overdose Death.
Paulozzi LJ, Kilbourne EM, Shah NG, Nolte KB, Desai HA, Landen MG, Harvey W, Loring LD.
Pain Med. 2011 Oct 25. doi: 10.1111/j.1526-4637.2011.01260.x.
Comment: Our understanding of opioid analgesic deaths is so poor for many reasons - most notably it is hard to study this population because they are hidden. The authors here used a case-control design (I can't access the full article and their methods are not so well-described in the abstract) to identify risk factors for death. They found receipt of prescriptions for selected opioids and >40mg morphine equivalents daily to be substantial risk factors for overdose death. This is consistent with earlier studies.

Green TC, Black R, Grimes Serrano JM, Budman SH, Butler SF.
PLoS One. 2011;6(11):e27244. Epub 2011 Nov 2.
Comment: This one takes a while to read through, but is intensely interesting. I highly recommend taking a close look at the article, the figures and tables, and even (!) digging through the entire text. Keep in mind this is a sample seeking substance abuse treatment - this is not an analysis of the general population of people who use prescription opioid.

Centers for Disease Control and Prevention (CDC)
MMWR Morb Mortal Wkly Rep. 2012 Jan 13;61:10-3.
Comment: This is watered down; I'm not sure of the message.

Khosla N, Juon HS, Kirk GD, Astemborski J, Mehta SH.
Addict Behav. 2011 Dec;36(12):1282-7. Epub 2011 Aug 5.
Comment: Lots of prescription opioid use among injectors.

Centers for Disease Controland Prevention (CDC).
MMWR Morb Mortal Wkly Rep.2012 Jul 6;61:493-7.
Comment: Methadone has been the likely culprit for a large portion of prescription opioid deaths in the U.S. in the past 8-9 years. This likely occurred for a couple of reasons. First, extended release oxycodone was associated with a surge in opioid overdose deaths 10-12 years ago, so switching to methadone as the long-acting opioid seemed reasonable at the time. Unfortunately, dosing of methadone is complicated, with a non-linear dose-response curve that makes doses over 30mg dangerous for methadone-naive patients. 

Gudin J.
J Pain Palliat Care Pharmacother. 2012 Jun;26(2):136-43.
Comment: I don't have access to this one, but it's an interesting piece on prescription opioids requirements emerging from the FDA. The Project Lazarus site has more information. 

Lankenau SE, Teti M, Silva K, Bloom JJ, Harocopos A, Treese M.
J Urban Health. 2012 Jun 9. [Epub ahead of print]
Comment: Very interesting qualitative piece on use of prescription opioids by young heroin injectors. One harm reduction strategy noted by study participants was to substitute prescription opioids for heroin when there was an outbreak of heroin overdose deaths in the community. 

Wang KH, Becker WC, Fiellin DA.
Drug Alcohol Depend. 2012 Jul 20. [Epub ahead of print]
Comment: Based on the 2008-2009 National Survey on Drug Use and Health, authors looked at nonmedical use of prescription opioids by county. Overall use rates were similar in urban and rural counties, with high rates of psychological distress and non-medical use of other prescription drugs.

Manchikanti L, Abdi S, Atluri S, et al.
Pain Physician. 2012 Jul;15(3 Suppl):S67-S116.
Comment: There are some nice summaries of current understanding related to prescription opioid overdose in this long paper. Although there is brief mention of the idea of using buprenorphine/naloxone combinations for opioid dependent persons with chronic pain, no mention is made of dispensing naloxone. Of note there is a contradiction in the paper: on page S74 authors write that the evidence that prescription drug monitoring programs reduce overdose is “poor”, then in the recommendation for such programs state that the evidence is “good to fair.”

Deschamps JY, Gaulier JM, Podevin G, Cherel Y, Ferry N, Roux FA.
Vet Anaesth Analg. 2012 Jul 13. doi: 10.1111/j.1467-2995.2012.00749.x. [Epub ahead of print]
Comment: Two primates were given fentanyl patches for post-operative anesthesia, they of course ate the patches, and they died. I’ll leave further comments to you.

Boyer EW.
N Engl J Med. 2012 Jul 12;367(2):146-55. Review. No abstract available.
Comment: A review of management of opioid analgesic overdose in emergency departments or hospitals.

ACOG Committee on Health Care for Underserved Women; American Society of Addiction Medicine.
Obstet Gynecol. 2012 May;119(5):1070-6.
Comment: A nice summary supporting established recommendations for opioid agonist maintenance therapy in pregnancy, noting both that tapering pregnant women off of opioids is dangerous and unnecessary and that breastfeeding is okay for women on agonist therapy.


Comment: A substantial contribution to the growing literature evaluating naloxone programs, this paper is a must-read for anyone interested in opioid overdose prevention.

Yokell MA, Green TC, Bowman S, McKenzie M, Rich JD.
Med Health R I. 2011 Aug;94(8):240-2.
Comment: A review of programmatic data from the Rhode Island naloxone distribution program

Bennett AS, Bell A, Tomedi L, Hulsey EG, Kral AH.
J Urban Health. 2011 Jul 20.
Comment: A very useful review of the PA naloxone distribution program, including the rate of survival among those administered naloxone.

Hurley R.
BMJ. 2011 Aug 25;343:d5445. doi: 10.1136/bmj.d5445. No abstract available.
Comment: A brief summary of the pilot program at drug treatment programs in England. 495 "carers" (generally family members) were trained and a subgroup (number not in the text) were also given naloxone in 2009 and 2010. Twenty ODs were witnessed and naloxone was given in 18 of those; all survived. These are important results, particularly in two settings: 1) regions where drug users frequently live with family, and 2) settings such as abstinence-based treatment or youth programs where there might be reluctance to provide a drug user with naloxone.

Wallisch M, El Rody NM, Huang B, Koop DR, Baker JR Jr, Olsen GD.
Respir Physiol Neurobiol. 2011 Oct 19.
Comment: I don't usually include animal studies, but this was intriguing. Authors developed a depot pro-drug of naloxone that is released in the setting of hypoxemia - that is, when there's a low-level of oxygen in the blood naloxone is released, reversing the (presumed) opiate effect.

Centers for Disease Control and Prevention (CDC).
MMWR Morb Mortal Wkly Rep. 2012 Feb 17;61:101-5.
Comment: Hooray! Read this for a review of U.S. nationwide naloxone program data.
Liu Y, Bartlett N, Li L, Lv X, Zhang Y, Zhou W.
Subst Abuse Treat Prev Policy. 2012 Feb 8;7(1):6. [Epub ahead of print]
Comment: Incarcerated drug users would like to have naloxone.

Gould M.
Nurs Stand. 2011 Nov 16-22;26(11):24-5.
Comment: I was only able to access this through my university account, but it is a really interesting discussion of the British prison-release take-home naloxone trial. Scotland dropped out and began routine naloxone distribution for all released prisoners. The ethics around the trial are complex - many doubt the need for proof while others point to the frustrating history of treatments assumed to work and later proven to be harmful. While it is true that similar interventions for other populations would not require proof for wide dissemination, broad application of naloxone distribution will be limited by the lack of randomized trial data.

Freise KJ, Newbound GC,Tudan C, Clark TP.
J Vet Pharmacol Ther. 2012Aug;35 Suppl 2:45-51.
Comment: Naloxone reverses this long-acting fentanyl solution in beagles. I'm not clear from this what the dose requirements are for naloxone in this situation.

Lankenau SE, Wagner KD, Silva K, Kecojevic A, Iverson E, McNeely M, Kral AH.
J Community Health. 2012 Jul 31. [Epub ahead of print]
Comment: An exciting article from a mixed methods study of Los Angeles area naloxone recipients. The authors note the possible need for booster sessions after naloxone distribution – an interesting idea that plays into the possible behavioral effect of naloxone. Hopefully this is the first of many such analyses.


Hedrich D, Alves P, Farrell M, Stöver H, Møller L, Mayet S.
Addiction. 2011 Sep 29. doi: 10.1111/j.1360-0443.2011.03676.x.
Comment: Some data that agonist maintenance therapy in prison reduces post-release overdose mortality

D'Amore A, Romano F, Biancolillo V, Lauro G, Armenante C, Pizzirusso A, Del Tufo S, Ruoppolo C, Auriemma F, Cassese F, Oliva P, Amato P.
Clin Drug Investig. 2012 May 4.
Comment: A dosing scale that includes non-fatal overdose as a marker for adjusting buprenorphine dosage. Again, I can't access the article to get details! I'd love comments from anyone who can.


Nielsen K, Nielsen SL, Siersma V, Rasmussen LS.
Resuscitation. 2011 Jun 15.
Comment: These data from Denmark again demonstrate the increasing risk of mortality among those who have overdosed multiple times

Nielsen K, Nielsen SL, Siersma V, Rasmussen LS.
Resuscitation. 2011 Nov;82(11):1410-3. Epub 2011 Jun 15.
Comment: Very useful review of opioid overdoses attended by emergency medical services in Copenhagen. Of 3245 cases, 69% were released at the scene without transport to the hospital, 11% had cardiac arrest at the scene, 21% were admitted to the hospital, and 10% died. These data seem pretty consistent with my current understanding of EMS attended overdoses. Nonetheless, I find these data intensely interesting because, notwithstanding many theories, we still don't really know what happens to the overdoses that occur in the community.
Rudolph SS, Jehu G, Nielsen SL, Nielsen K, Siersma V, Rasmussen LS.
Resuscitation. 2011 Nov;82(11):1414-8. Epub 2011 Jul 2.
Comment: This is a sub-analysis of the prior study. They looked at the 69% of people that were released after naloxone was given and not transported to the hospital. They found that 3 of 2241 individuals died from a suspected "rebound overdose" after naloxone was given. Put in other words, 0.1% of overdose victims who were given naloxone at the scene and then released fell back into an opioid overdose and died. The authors looked pretty deeply into the circumstances post-release, so I think these data are reliable. While this figure is impressively low, it does reaffirm the need for bystanders to stay with overdose victims for several hours after reversing an overdose.

Weber JM, Tataris KL, Hoffman JD, Aks SE, Mycyk MB.
Prehosp Emerg Care. 2011 Dec 22.
Comment: Nebulized naloxone is an interesting option for emergency medical services, although not widely available as a means of lay administration.


Christian G, Pike G, Santamaria J, Reece S, DuPont R, Mangham C.
Lancet. 2012 Jan 14;379(9811):117; author reply 118-9. No abstract available.
Comment: An interesting critique of the seminal paper on the overdose fatality reduction associated with Vancouver's supervised injection facility. The authors' response appears to effectively belie the critique.

Semaan S, Fleming P, Worrell C, Stolp H, Baack B, Miller M.
Drug Alcohol Depend. 2011 Nov 1;118(2-3):100-10. Epub 2011 Apr 23.
Comment: A review of data on supervised injection facilities, which have impressive data on reducing local overdose mortality in Vancouver.

Yokell MA, Zaller ND, Green TC, McKenzie M, Rich JD.
J Opioid Manag. 2012 Jan-Feb;8(1):63-6.
Comment: Buprenorphine is a partial agonist with a ceiling effect that limits the capacity for overdose among those with a tolerance to opioids. Like naloxone, buprenorphine really likes binding to opioid receptors and kicks most other opioids out. Since buprenorphine out-competes other opioids for receptors and has a ceiling effect, administration in the setting of overdose may result in reversal of opioid overdose. That said, this wouldn't be the approach I would advocate for dissemination since (1) buprenorphine could cause overdose in an opioid user with minimal tolerance and (2) buprenorphine could cause prolonged withdrawal (for over a day) in those with a very high tolerance.

Goli V, Webster LR, Lamson MJ, Cleveland JM, Sommerville KW, Carter E.
Harm Reduct J. 2012 Mar 15;9(1):13. [Epub ahead of print]
Comment: An intriguing analysis of whether or not injecting the pre-formulated morphine + naltrexone actually blocks the effects of morphine. It appears to partially, but not completely, block the effect.

Small D.
Harm Reduct J. 2012 Jul 20;9(1):34. [Epub ahead of print]
Comment: A review of the 2011 Supreme Court of Canada decision supporting the Vancouver supervised injection facility.


  1. Excellent roundup, Phillip! Thanks for posting it.

  2. This review of individuals seeking treatment in Australia found that, compared to heroin users, prescription opioid users were roughly 10% less likely to report a history of overdose and over twice as likely to report initial use for pain control.
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  3. A very useful overview for anyone designing a Naloxone pilot. Thank you.