PubMed Update September 2013

12 articles this month.

1) Effectiveness of Naltrexone in the Prevention of Delayed Respiratory Arrest in Opioid-Naive Methadone-Intoxicated Patients.

Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, Shadnia S, Mashayekhian M, Rahimi M, Nasouhi S, Ghoochani A.

Biomed Res Int. 2013;2013:903172. Epub 2013 Sep 9.

Comments: Interesting use of the long-acting opioid antagonist naltrexone in this study from Iran. The likely downside of this approach of course is that, in those with opioid dependence (constituting the vast majority of overdose cases), it doesn’t allow for titration of antagonist effect to minimize withdrawal symptoms.

2) An investigation of the interactions between methadone and elvitegravir/cobicistat in subjects receiving chronic methadone maintenance.

Bruce RD, Winkle P, Custodio JM, Wei X, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

Antimicrob Agents Chemother.2013 Sep 30. [Epub ahead of print]

Comments: This is a promising finding for the new HIV regimen.

3) Interaction of Different Antidepressants with Acute and Chronic Methadone in Mice, and Possible Clinical Implications.

Schreiber S, Barak Y, Hostovsky A, Baratz-Goldstein R, Volis I, Rubovitch V, Pick CG.

J MolNeurosci.2013 Sep 22. [Epub ahead of print]

Comments: Really interesting study, since many opioid overdoses occur in the presence of anti-depressant medications. These results are too preliminary to draw strong conclusions, but it’s an important pursuit.

4) Law enforcement attitudes toward overdose prevention and response.

Green TC, Zaller N, Palacios WR, Bowman SE, Ray M, Heimer R, Case P.

Drug Alcohol Depend.2013 Sep 2.doi:pii: S0376-8716(13)00334-7. 10.1016/j.drugalcdep.2013.08.018. [Epub ahead of print]

Comments: Interesting qualitative analysis of police attitudes toward lay naloxone.

5) Days of heroin use predict poor self-reported health in hospitalized heroin users.

Meshesha LZ, Tsui JI, Liebschutz JM, Crooks D, Anderson BJ, Herman DS, Stein MD.

Addict Behav. 2013 Aug 14;38(12):2884-2887. doi:

Comments: More days of heroin use is associated with worse self-reported health and worse self-reported health is associated with non-fatal overdose events.

6) Assisted injection among people who inject drugs in Thailand.

Lee WK, Ti L, Hayashi K, Kaplan K, Suwannawong P, Wood E, Kerr T.

Subst Abuse Treat Prev Policy. 2013 Sep 10;8(1):32. [Epub ahead of print]

Comments: This is a useful contribution to overdose literature. There has long been a concern that people who require assistance to inject (often women) would overdose more. This hasn’t held up in studies and this study corroborates that lack of association. It may be well worth exploring further, but thus far we don’t have any evidence that assistance with injecting increases overdose risk.

7) BET 3: Is nebulised naloxone effective in opioid overdose?

[No authors listed]

Emerg Med J. 2013 Oct;30(10):860. doi: 10.1136/emermed-2013-203100.3.

Comments: Yes, in breathing patients.

8) The lethal burden of drug overdose.

[No authors listed]

Lancet. 2013 Sep 7;382(9895):833. doi: 10.1016/S0140-6736(13)61844-9. No abstract available.

Comments: Brief commentary on opioid overdose mortality in UK and US. Notable that there is no mention of naloxone.

9) [Maintaining opioid abstinence long after inpatient treatment with opioid substitution in an addictology hospital unit].

Bouab O, Lahmek P, Meunier N, Aubin HJ, Michel L.

Rev Med Brux. 2013 May-Jun;34(3):132-40. French.

Comments: Basically inpatient withdrawal from agonist maintenance treatment.

10) The pharmacokinetic and pharmacodynamic interactions between buprenorphine/naloxone and elvitegravir/cobicistat in subjects receiving chronic buprenorphine/naloxone treatment.

Bruce RD, Winkle P, Custodio JM, Wei LX, Rhee MS, Kearney BP, Ramanathan S, Friedland GH.

J Acquir Immune DeficSyndr. 2013 Aug 1;63(4):480-4. doi: 10.1097/QAI.0b013e3182961d31.

Comments: The new combined HIV med (Stribild) modestly increases buprenorphine levels.

11) Problem based review: The patient taking methadone.

Arora A, Williams K.

Acute Med. 2013;12(1):51-4. Review.

Comments: Methadone maintenance review.

12) Low-frequency heroin injection among out-of-treatment, street-recruited injection drug users.

Harris JL, Lorvick J, Wenger L, Wilkins T, Iguchi MY, Bourgois P, Kral AH.

J Urban Health. 2013 Apr;90(2):299-306. doi: 10.1007/s11524-012-9720-8.

Comments: Another useful contribution – infrequent heroin injectors had a lower risk of non-fatal overdose. As with most overdose epidemiology, the relationship between use frequency and overdose risk is likely complex.

PubMed Update: Another Year in Overdose

Another year in overdose, September 2012-August 2013, generally in reverse chronological order, and following the same loosely-formed categories as last year. 

Once again, this is opioid focused and misses anything not listed in the PubMed database – which means it misses many interesting papers to which you are warmly welcomed to post links!

This year there were 99 papers, up from 81 in the preceding 12 months. 

PubMed Update August 2013

16 papers today – this is getting to be a big job. Naloxone, fentanyl, methadone, stars, pain, Central Asia, primary care, injection facilities, personal stories …

1) Notes from the field: acetyl fentanyl overdose fatalities - rhode island, march-may 2013.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2013 Aug 30;62(34):703-4.

Comment: The evidence of synthetic fentanyl was difficult to detect and concerning to many as heralding a possible repeat of the 2006/2007 fentanyl-tainted heroin overdose outbreak.

2) Methadone induced sensorineural hearing loss.

Saifan C, Glass D, Barakat I, El-Sayegh S.

Case Rep Med. 2013;2013:242730. doi: 10.1155/2013/242730. Epub 2013 Jul 29.

Comment: In this case the patient was restarted on methadone and the sensorineural hearing loss was permanent.

3) Opioids compared to placebo or other treatments for chronic low-back pain.

Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC.

Cochrane Database Syst Rev. 2013 Aug 27;8:CD004959. doi:

Comment: There are no quality data to support long-term management of non-cancer pain with opioids.

4) Cory monteith dies of a heroin overdose at age 31.

Willens JS.

Pain Manag Nurs. 2013 Sep;14(3):125. doi: 10.1016/j.pmn.2013.07.004. No abstract available.

Comment: The Glee star.

PubMed Update July 2013

8 papers this month. Police, pharmacology, prisons, methadone, money, and plants. Enjoy!

1) Police Officers' and Paramedics' Experiences with Overdose and Their Knowledge and Opinions of Washington State's Drug Overdose-Naloxone-Good Samaritan Law.

Banta-Green CJ, Beletsky L, Schoeppe JA, Coffin PO, Kuszler PC.

J Urban Health. 2013 Jul 31. [Epub ahead of print]

Comment: Expands on the limited data we have regarding police and paramedics knowledge and opinions regarding opioid overdose prevention initiatives.

2) [Heroin].

Demaret I, Lemaître A, Ansseau M.

Rev Med Liege. 2013 May-Jun;68(5-6):287-93. French.

Comment: Only saw the abstract, but appears to be a nice summary of heroin, particularly overdose risk factors.

3) Potential P-glycoprotein Pharmacokinetic Interaction of Telaprevir With Morphine or Methadone.

Fudin J, Fontenelle DV, Fudin HR, Carlyn C, Hinden DA, Ashley CC.

J Pain Palliat Care Pharmacother. 2013 Jul 24. [Epub ahead of print]

Comment: Some potential interactions of the HCV protease inhibitor with selected opioids. Hopefully we won’t be using telaprevir too much longer as more advanced, effective, and easily tolerated regimens are expected as early as the end of 2013.

4) Non-fatal overdose among adult prisoners with a history of injecting drug use in two Australian states.

Moore E, Winter R, Indig D, Greenberg D, Kinner SA.

Drug Alcohol Depend. 2013 Jul 15. doi:pii: S0376-8716(13)00220-2.

Comments: Survey of prisoners lifetime history of overdose.

5) Factors associated with high-frequency illicit methadone use among rural Appalachian drug users.

Hall MT, Leukefeld CG, Havens JR.

Am J Drug Alcohol Abuse. 2013 Jul;39(4):241-6. doi:

Comment: I can’t access this article, but have some concerns about the utility of the analysis of covariates presented in the abstract.

6) Methadone-Related Overdose Deaths in Rural Virginia: 1997 to 2003.

Wunsch MJ, Nuzzo PA, Behonick G, Massello W, Walsh SL.

J Addict Med. 2013 Jul 8. [Epub ahead of print]

Comments: Analysis of methadone-related deaths.

7) The Economic Burden of Opioid-Related Poisoning in the United States.

Inocencio TJ, Carroll NV, Read EJ, Holdford DA.

Pain Med. 2013 Jul 10. doi: 10.1111/pme.12183. [Epub ahead of print]

Comments: Intriguing analysis of costs of opioid overdose, focusing on the costs to the healthcare system.

8) A drug fatality involving Kratom.

Neerman MF, Frost RE, Deking J.

J Forensic Sci. 2013 Jan;58 Suppl 1:S278-9. doi: 10.1111/1556-4029.12009. Epub 2012 Oct 19.

Comments: Kratom is a plant that grows in North America (this case is from Texas) and many other parts of the world. Its use is prohibited in Thailand. It acts as a mu-opioid receptor agonist.

Naloxone laws to reduce overdose - update

Back by popular demand is the map of U.S. states with legislation improving lay naloxone access. This post was delayed by a very active legislative season which I think has slowed down for the moment. As usual, this may have errors so please comment and I'll correct. 

This time I've only included states on the map (in black) with existing legislation improving lay naloxone access (e.g. not Oklahoma and Ohio as those bills target first responder access to naloxone, and not pending legislation that improves access in states - like California - that already have it). There are now lay naloxone access laws in CA, CO, CT, IL, KY, MA, MD, NJ, NC, NM, NY, OR, RI, VA, VT, WA, and the District of Columbia.

Unsuccessful bills this season included Maine and West Virginia.


Here's a summary from the Network for Public Health Law of naloxone (and Good Samaritan) laws that is kept regularly updated.

PubMed Update June 2013

13 new papers this month, from drug development to naloxone programming, epidemiology to practice management, toxicology to supply side drug control.

1) Illicit drug overdose - Prevalence and acute management.

Li W, Gunja N.

Aust Fam Physician. 2013 Jul;42(7):481-5.

Comment: Unable to access.  Appears to be a general review of managing illicit drug toxicities.

2) Development and implementation of an opioid overdose prevention and response program in Toronto, Ontario.

Leece PN, Hopkins S, Marshall C, Orkin A, Gassanov MA, Shahin RM.

Can J Public Health. 2013 Apr 18;104(3):e200-4.

Comment: Unable to access. There have been several papers describing the initial experience of naloxone programs and this is a welcome addition to that literature.

3) Vital signs: overdoses of prescription opioid pain relievers and other drugs among women - United States, 1999-2010.

Centers for Disease Control and Prevention (CDC).

MMWR Morb Mortal Wkly Rep. 2013 Jul 5;62(26):537-42.

Comment: A review of drug overdose mortality data among women, demonstrating that women have been particularly affected by the recent epidemic.

4) Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal in Russian cities.

Coffin PO, Sullivan SD.

J Med Econ. 2013 Jun 19. [Epub ahead of print]

Comments: An adaptation of the model developed for the United States, taking into account structural differences, epidemiologic data, and costs in Russia. Because of limitations in emergency medical services in Russia, the high rate at which overdoses are witnessed, and the very low costs of naloxone, this intervention is likely to be even more cost-effective in Russia than it appears to be in the United States.

New site NaloxoneInfo.org is chockablock with overdose prevention resources

Interested in learning more about opioid overdose and how to build prevention projects? The recently launched NaloxoneInfo.org site is worth a look. Made live during the International Harm Reduction Conference in June 2013, the site was developed by the Open Society Foundations in collaboration with Population Services International, Harm Reduction International, the Eurasian Harm Reduction Network, the Scottish Drugs Forum, Harm Reduction Coalition, and the Asian Network of People Who Use Drugs. 

The site is currently available in English and Russian and includes background information on overdose by region, a number of useful case studies, and tons of freely downloadable program, training, and advocacy materials that should help anyone starting a project. 

New Film: "Reach for Me: Fighting to End America's Drug Overdose Epidemic"

I posted on OPA recently with a preview cut, and I'm very happy to say that we've now launched the final version of our film Reach for Me: Fighting to End America's Drug Overdose Epidemic and our accompanying website. The film  looks at how naloxone pricing, production shortages, and the lack of government support are affecting overdose prevention efforts around the United States. 

We interviewed 30 people, including a number of regular OPA contributors, representing California, Colorado, Connecticut, DC, Louisiana, Michican, Minnesota, New York, North Carolina, Oregon, Wisconsin and more. In addition to the full length (but still just 15 min!) film, we're posting everyone's complete interviews, as well as, soon, a 3 minute version.  

The goal is to use the film as a platform for education and advocacy in order to push for universal access to opioid overdose prevention education and take-home naloxone for those who need it. To that end, over coming weeks on the website we'll be rolling out more advocacy tools and a petition aimed at U.S. federal funding. 

The film was produced by Sawbuck Productions, a Chicago-based nonprofit documentary film company that works on issues related to harm reduction, and which is headed up by Greg Scott & Erin Scott. Eliza Wheeler of HRC and the DOPE Project also contributed magnificently, and Nigel Brunsdon of the UK-based Injecting Advice and HIT did the website. The Open Society Foundations generously contributed to production and distribution costs.  

Help us spread the word further by liking our Facebook page (www.facebook.com/reach4me) and following us on Twitter (@reach4us). We especially want to build awareness outside the harm reduction community.  

For those of you in the U.S., if you'd like a copy on DVD, please follow this link. We'd also be happy to arrange local screenings and discussion -- please be in touch through the contact link on the reach4me.org site if you'd like to do so.

Preview Cut Now Available: "Reach for Me: Fighting to End the American Drug Overdose Epidemic"

Late last year we posted about seeking people to interview for a short documentary film about access to naloxone in the United States. The results are now available in a preview (aka not-quite-final-but-almost) cut of Reach for Me: Fighting to End the American Drug Overdose Epidemic.  Please have a look and tell us what you think! 

The film explores the interconnected issues of naloxone pricing and production shortages, public funding support (or more often lack thereof), and other factors affecting access to overdose prevention tools. It features interviews with leading experts and advocates from around the country, including California, Minnesota, New York, North Carolina, Oregon, Washington, DC, and Wisconsin. 


The point, for us, is to use Reach for Me as a platform for building awareness, understanding, and support for overdose prevention programs. To that end, over the next couple weeks we'll be rolling out the final version of the film, a short (c. 3 minute) version, along with a website and Facebook and Twitter pages. The film will be freely available on DVD (follow this link to request up to 20 copies) and online for streaming or download. We'll also be making available the full interviews with the nearly 30 people who participated. Stay tuned!

Elizabeth Owens of VOCAL New York
in a scene from Reach for Me

The film was directed by Greg Scott, and produced by Matt Curtis and Erin Scott, with an assist from Eliza Wheeler, and was produced under the aegis of Sawbuck Productions. We'd like to thank everyone involved, and especially the Open Society Foundations for their financial support and the Harm Reduction Coalition for allowing us to film during their excellent biennial conference. 

Chicago Recovery Alliance and Gateway Foundation 

Begin Opioid OD Prevention in Cook County Jail

On Tuesday June 11, 2013, Ashley Tsang (a UChicago Medical Student and Schweitzer Fellow) and Dan Bigg, CRA's Director met with Mike Colombatto, PsyD Program Administrator at Gateway Foundation's Treatment System at Cook County Jail regarding integrating opioid overdose at the Jail.  Ashley concluded from research that non-dependent opioid users leaving corrections had over 100 times the risk of death through overdose as ordinary citizens.

A quick meeting of the minds was had and Ashley and Dan began trainings at Cook County Jail's Gateway Treatment System's two programs (Day Treatment and Pre-Release residential settings).

The OD trainings on June 13 and 14, 2013 were very well received showing the majority of individuals there had been around opioid overdose and nearly a third had been around a fatal such OD.

Plans are to continue these trainings and improve the process of making OD preventative options readily available to all tolerance-lessened individuals and those around opioid users under IL's OD Program law (20 ILCS 301/5-23) which allows lay persons to become OD Responders and carry and use naloxone via injection.

We are delighted with this life affirming progress in Chicago and thank our colleagues in Pittsburgh, Rhode Island, and San Francisco among others for their guidance and other assistance with this effort.

PubMed Update May 2013

Here is the May 2013 roundup with 7 papers and some extra kudos to the authors for important steps forward in data or practice.

1) Ethanol Reversal of Cellular Tolerance to Morphine in Rat Locus Coeruleus Neurons.

Llorente J, Withey S, Rivero G, Cunningham M, Cooke A, Saxena K, McPherson J, Oldfield S, Dewey W, Bailey C, Kelly E, Henderson G.

Mol Pharmacol. 2013 May 28. [Epub ahead of print]

Comments: Intriguing analysis of ethanol and morphine, suggesting that alcohol may enhance the effects of morphine. Could this account for some of the risk of combining opioids with alcohol?

2) Hypoglycemia during rapid methadone dose escalation.

Moryl N, Pope J, Obbens E.

J Opioid Manag. 2013 Jan-Feb;9(1):29-34. doi: 10.5055/jom.2013.0144.

Comments: One of a handful of issues with methadone dosing that may have factored into the challenges encountered by providers and patients with this drug when used for pain.

3) Benzodiazepine use during buprenorphine treatment for opioid dependence: Clinical and safety outcomes.

Schuman-Olivier Z, Hoeppner BB, Weiss RD, Borodovsky J, Shaffer HJ, Albanese MJ.

Drug Alcohol Depend. 2013 May 17. doi:pii: S0376-8716(13)00133-6. 10.1016/j.drugalcdep.2013.04.006. [Epub ahead of print]

Comments: For patients on any opioid medications, benzodiazepines are associated with an increased risk of overdose. This study of 328 buprenorphine maintenance patients didn’t find an association with benzodiazepine prescriptions and overdose, but did find an association with more frequent emergency department visits and injury-related ED visits. We may never learn if benzodiazepines are causal in this pathway or merely a marker, but these data do contribute to the overall concern.

4) The relationship between age and risky injecting behaviours among a sample of Australian people who inject drugs.

Horyniak D, Dietze P, Degenhardt L, Higgs P, McIlwraith F, Alati R, Bruno R, Lenton S, Burns L.

Drug Alcohol Depend. 2013 May 9. doi:pii: S0376-8716(13)00116-6. 10.1016/j.drugalcdep.2013.03.021. [Epub ahead of print]

Comments: More excellent work from this team. I particularly appreciate the estimate of the reduction in overdose risk with age. In a mathematical model of overdose, we estimated a 50% reduction in the risk of overdose over 10 years of use, whereas this paper suggests the figure is closer to 20% - data that will be very helpful in future iterations.

5) Reducing the Health Consequences of Opioid Addiction in Primary Care.

Bowman S, Eiserman J, Beletsky L, Stancliff S, Bruce RD.

Am J Med. 2013 May 8. doi:pii: S0002-9343(13)00138-1. 10.1016/j.amjmed.2012.11.031. [Epub ahead of print]

Comments: Congratulations to this team on producing what I think are the first primary care guidelines in the scientific literature recommending overdose prevention and naloxone for at-risk patients.

6) Acute Pain Control Challenges with Buprenorphine/Naloxone Therapy in a Patient with Compartment Syndrome Secondary to McArdle's Disease: A Case Report and Review.

McCormick Z, Chu SK, Chang-Chien GC, Joseph P.

Pain Med. 2013 May 3. doi: 10.1111/pme.12135. [Epub ahead of print]

Comments: Less an overdose article per se, but a paper that pays attention to the overdose issue when titrating opioids.

7) Barriers to medical provider support for prescription naloxone as overdose antidote for lay responders.

Green TC, Bowman SE, Zaller ND, Ray M, Case P, Heimer R.

Subst Use Misuse. 2013 May;48(7):558-67. doi: 10.3109/10826084.2013.787099.

Comments: A qualitative look at providers feelings about providing naloxone to “drug users” and, separately, to “pain patients.” This is a great and useful analysis – and honestly surprisingly positive across the board. The major concern raised seemed to be that naloxone not be the only thing done to try to reduce overdose. This is a pretty dramatic shift in attitudes since earlier evaluations of provider opinion on lay naloxone (Beletsky et al 2007, Coffin et al 2003).

PubMed Update April 2013

10 papers this time. Good stuff.

1. Take-Home Emergency Naloxone to Prevent Heroin Overdose Deaths after Prison Release: Rationale and Practicalities for the N-ALIVE Randomized Trial.

Strang J, Bird SM, Parmar MK.

J Urban Health. 2013 May 1. [Epub ahead of print]

Comment: Really interesting article on the design of the N-ALIVE trial of naloxone provision to prisoners pre-release.

2. Determination of dextromethorphan and levomethorphan in seized heroin samples by enantioselective HPLC and electronic CD.

Tedesco D, Di Pietra AM, Rossi F, Garagnani M, Del Borrello E, Bertucci C, Andrisano V.

J Pharm Biomed Anal. 2013 Apr 6;81-82C:76-79. doi: 10.1016/j.jpba.2013.03.024. [Epub ahead of print]

Comment: Methods paper demonstrating methorphan in some heroin samples involved in overdose death.

3. All-cause mortality in criminal justice clients with substance use problems-A prospective follow-up study.

Hakansson A, Berglund M.

Drug Alcohol Depend. 2013 Apr 24. doi:pii: S0376-8716(13)00109-9. 10.1016/j.drugalcdep.2013.03.014. [Epub ahead of print]

Comments: Another analysis of post-release mortality among prisoners, in which the largest group (39%) of deaths were due to accidental or undetermined intent poisoning.

4. Changing law from barrier to facilitator of opioid overdose prevention.

Davis C, Webb D, Burris S.

J Law Med Ethics. 2013 Mar;41 Suppl 1:33-6. doi: 10.1111/jlme.12035.

Comments: Excellent analysis of naloxone and Good Samaritan legislation.

Naloxone: Keep it with your lipstick

Excellent "Here and Now" radio story on naloxone in Massachusetts and administration by parents!

 

Mother Saves Her Son From Overdose Thanks To Pilot Program