PubMed Update August 2015

Sixteen in August. Back on schedule (thanks to jetlag).

1) Reducing Fatal Opioid Overdose: Prevention, Treatment and Harm Reduction Strategies.

Hawk KF, Vaca FE, D'Onofrio G.

Yale J Biol Med. 2015 Sep 3;88(3):235-245. eCollection 2015 Sep. Review.

Comment: Can’t access full article. Appears to be a review of harm reduction strategies for opioid overdose prevention.

2) Prescription Opioid Misuse, Abuse, and Treatment in the United States: An Update.

Brady KT, McCauley JL, Back SE.

Am J Psychiatry. 2015 Sep 4:appiajp201515020262. [Epub ahead of print]

Comment: Appropriately draws attention to the problem now faced in the United States: we are cutting back on opioid prescribing to try to limit further opioid dependence, but effectively abandoning many of the people who are already dependent.

3) Sleep-disordered breathing in patients with opioid use disorders in long-term maintenance on buprenorphine-naloxone: A case series.

DeVido J, Connery H, Hill KP.

J Opioid Manag. 2015 Jul-Aug;11(4):363-6. doi: 10.5055/jom.2015.0285.

Comment: Two case reports of sleep-disordered breathing among buprenorphine patients suggesting that buprenorphine may contribute to sleep apnea.

4) Buprenorphine infrequently found in fatal overdose in New York City.

Paone D, Tuazon E, Stajic M, Sampson B, Allen B, Mantha S, Kunins H.

Drug Alcohol Depend. 2015 Aug 15. pii: S0376-8716(15)01598-7. doi: 10.1016/j.drugalcdep.2015.08.007. [Epub ahead of print]

Comment: Actually, none of the decedents tested positive for buprenorphine - very few (2) were found to have positive toxicology for norbuprenorphine, a metabolite demonstrating recent – but not recent enough to be causal – consumption of buprenorphine. This is not surprising since it’s tough to overdose on buprenorphine. Nice work.

5) Risk Factors for Mortality and Endotracheal Intubation after Methadone Intoxication.

Hassanian-Moghaddam H, Soltaninejad K, Shadnia S, Kabir A, Movahed M, Mirafzal A.

Basic Clin Pharmacol Toxicol. 2015 Aug 24. doi: 10.1111/bcpt.12476. [Epub ahead of print]

Comment: Lower consciousness/respirations once in the emergency room were associated with increased likelihood of being intubated and/or dying from methadone overdose. This is interesting in the context of previous papers included on this blog that demonstrate lower likelihood of such outcomes when naloxone is administered in the field. Is it time to think of naloxone as an automated electronic defibrillator?

6) The characteristics of a cohort who tamper with prescribed and diverted opioid medications.

Larance B, Lintzeris N, Bruno R, Peacock A, Cama E, Ali R, Kihas I, Hordern A, White N, Degenhardt L.

J Subst Abuse Treat. 2015 Jun 24. pii: S0740-5472(15)00137-3. doi: 10.1016/j.jsat.2015.06.001. [Epub ahead of print]

Comment: This is a complex population. Although risk outcomes appear closer to those of someone who uses heroin than those of someone prescribed opioids, the clinical characteristics overlap substantially with the latter group.

PubMed Update August-October 2014

Three months. 32 articles. Enough said.

1. Patterns and correlates of non-fatal heroin overdose at 11-year follow-up: Findings from the Australian Treatment Outcome Study.

Darke S, Marel C, Mills KL, Ross J, Slade T, Burns L, Teesson M.

Drug Alcohol Depend. 2014 Sep 16. [Epub ahead of print]

Comment: This study (the ATOS) and the team of investigators have produced some of the most powerful and useful data in substance use research. Once again they have delved into heroin overdose by following treatment patients 11 years out. At least 10.2% of the cohort had died by that time and an additional 9.4% were unaccounted for. Among the 70.1% interviewed, 67.5% had overdosed, 24.4% had experienced five or more overdoses (again suggesting that there are “overdosers” out there who are at very elevated risk of the event). In the past year before the follow-up visit, 4.9% had overdosed (11.8% of those who had used heroin in that period), 95.2% of whom had overdosed previously. Those who overdosed were more likely to report higher levels of non-heroin opiate use, as well as benzodiazepine, cocaine, and methamphetamine use.

2. A new naloxone auto-injection device to treat opioid overdose.

Simonson W.

Geriatr Nurs. 2014 Sep-Oct;35(5):381-2.

Comment: A review of the role of take-home naloxone in the form of the new autoinjector.

3. Increases in heroin overdose deaths - 28 States, 2010 to 2012.

Rudd RA, Paulozzi LJ, Bauer MJ, Burleson RW, Carlson RE, Dao D, Davis JW, Dudek J, Eichler BA, Fernandes JC, Fondario A, Gabella B, Hume B, Huntamer T, Kariisa M, Largo TW, Miles J, Newmyer A, Nitcheva D, Perez BE, Proescholdbell SK, Sabel JC, Skiba J, Slavova S, Stone K, Tharp JM, Wendling T, Wright D, Zehner AM.

MMWR Morb Mortal Wkly Rep. 2014 Oct 3;63(39):849-54.

Comment: This report demonstrates declining prescription opioid deaths (-6.6%), but heroin deaths increased so much (+101.7%) that the data actually demonstrate an overall increase in opioid overdose mortality from 2010 to 2012 (+4.3%). There is disagreement as to what is driving the increase in heroin use and overdose. Is it an inevitable consequence of increased availability of opioids? Or is it the result of growing restrictions on access to those opioids? Clearly there are elements of both, leaving us with conflicting duties when it comes to managing those already reliant upon prescription opioids. Western medical ethics is clear on this point: our patient is the person we treat, who may have been harmed by the very same prescribing behavior we are now trying to change and who may be further harmed by those changes. If we truly believe that this epidemic is “iatrogenic” (i.e. caused by medical care, akin to a surgeon leaving scissors in an abdomen), then we have to be extremely cautious and thoughtful in fixing the problem and we can never abandon the patient.

4. Working together: Expanding the availability of naloxone for peer administration to prevent opioid overdose deaths in the Australian Capital Territory and beyond.

Lenton S, Dietze P, Olsen A, Wiggins N, McDonald D, Fowlie C.

Drug Alcohol Rev. 2014 Oct 1. doi: 10.1111/dar.12198. [Epub ahead of print]

Comment: It's taken an incredibly long time for take-home naloxone to reach Australia, especially given how innovative that country has been with respect to managing drug policy and overdose.

5. Responding to opioid overdose in Rhode Island: where the medical community has gone and where we need to go.

Green TC, Bratberg J, Dauria EF, Rich JD.

R I Med J (2013). 2014 Oct 1;97(10):29-33.

Comment: The first of three articles in this post from Rhode Island, US, which has been facing a surge in opioid overdose deaths and has been responding with expanded naloxone treatment availability. This and the next two articles are free at: http://rimed.org/rimedicaljournal-2014-10.asp.

PubMed Update November/December 2013

We close out 2013 with an impressive 25 papers in the final two months for a total count of 89 papers. Some interesting new approaches and perspectives, including a paper on the underappreciated role of adulterants, a couple of naltrexone papers, and lots of lay naloxone.

1) The Whole Is Just the Sum of Its Parts: Limited Polydrug Use Among the "Big Three" Expensive Drugs in the United States.

Caulkins JP, Everingham S, Kilmer B, Midgette G.

Curr Drug Abuse Rev. 2013 Dec 5. [Epub ahead of print]

Comments: Somewhat surprising data suggesting relatively separate markets for heroin, cocaine and methamphetamine.

2) A systematic review and meta-analysis of naltrexone implants for the treatment of opioid dependence.

Larney S, Gowing L, Mattick RP, Farrell M, Hall W, Degenhardt L.

Drug Alcohol Rev. 2013 Dec 3. doi: 10.1111/dar.12095. [Epub ahead of print]

Comments: A systematic review concluding that the data for naltrexone implants for opioid dependence are insufficient for use outside of clinical trials.

3) Trends and Regional Variation in Opioid Overdose Mortality Among Veterans Health Administration Patients, Fiscal Year 2001 to 2009.

Bohnert AS, Ilgen MA, Trafton JA, Kerns RD, Eisenberg A, Ganoczy D, Blow FC.

Clin J Pain. 2013 Nov 25. [Epub ahead of print]

Comments: What happened with opioid analgesic overdose deaths in the United States also happened in among veterans receiving care in the Veterans’ Administration.

4) The Dueling Obligations of Opioid Stewardship.

Coffin P, Banta-Green C.

Ann Intern Med. 2013 Dec 10. doi: 10.7326/M13-2781. [Epub ahead of print] No abstract available.

Comments: Commentary on the reliance on opioids and minimizing the potential harms of stewardship efforts.

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.

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.

New Resource! HRC Guide to Developing and Managing Overdose Prevention Projects

Just in time for the holiday season, the Harm Reduction Coalition has an excellent new Guide to Developing and Managing Overdose Prevention and Take-Home Naloxone Projects. This is the best thing I've seen so far on the subject, and while it focuses on the experience of programs in the Unites States, most of the information in the manual should be relevant worldwide. 

Follow the link to download the manual as well as other resources, worksheets and appendices. Print copies should be ready soon and can be had by contacting HRC through their website.

Capitalism Casts Its Gaze Upon Overdose Prevention

If you hang around long enough, the market will find you. And in an unanticipated but probably inevitable turn, we have what may be the first ever pharmaceutical advertisement aimed at community-based overdose prevention programs. Seen below, it's from LMA North America, which produces the nasal atomizer device used by most or all programs in the USA that distribute intranasal naloxone. This is a great thing, a clear sign that U.S. programs have reached a mass big enough that business needs to pay attention to them. Hopefully part of this development will be increasing leverage to negotiate better naloxone prices and delivery products.

Thanks to Eliza Wheeler of the amazing DOPE Project for passing on the advertisement. 

National Association of Drug Diversion Investigators Supports Naloxone Access

We've had a lot of success in bringing public health and medical agencies onboard with overdose prevention, and it's all the more exciting to see other pieces of the picture fall into place. On the law enforcement front, the U.S. National Association of Drug Diversion Investigators (NADDI) has issued a position statement encouraging police and other law enforcement officers to carry and be trained in the use of naloxone. As they write:

It is the opinion of the NADDI Executive Board that the ready availability of this product will ultimately save many lives, as police officers are oftentimes the first responders where delays of only a few seconds can mean the difference between life and death. 

That's the heart of the matter and why we need more cops to understand and be involved in overdose prevention. Overdose projects involving police have been working for years in New Mexico and have more recently saved lives on Long Island, New York and in Massachusetts.

NADDI is a national nonprofit organization that provides training and "facilitates cooperation between law enforcement, healthcare professionals, state regulatory agencies, pharmaceutical manufacturers in the investigation and prevention of prescription drug abuse and diversion." 

Overdose Prevention Legislation Introduced in U.S. House of Representatives

On August 2, Maryland Democratic Congresswoman Donna Edwards introduced the "Stop Overdose Stat (SOS) Act" to the U.S. House with bipartisan cosponsorship. The bill is an expanded version of legislation that Edwards introduced but failed to pass in 2009. With any luck the increased attention to overdose at the federal level and greater bipartisan involvement in the drafting of the current bill (particularly with leadership from California Republican Mary Bono Mack) will get it the consideration it deserves.


The full text of the bill is available on GovTrack here. In its current form the bill would establish four important things at the federal level:

• A grant program, to be administered by the Centers for Disease Control and Prevention (CDC), supporting overdose prevention work including naloxone distribution. Government public health agencies and community-based organizations would be eligible. 

• An overdose surveillance system whereby CDC would aggregate and analyze overdose data from local, state and federal government agencies and private sources. Such data could potentially fill gaps in information and provide a consistent way of spotting national trends that can help direct resources and programming. Crucially, the bill would also direct CDC to provide surveillance technical assistance to local and state agencies, which could spur more detailed and accurate reporting.

• Development of a national plan to reduce overdose mortality, to be submitted to Congress by the Secretary for Health and Human Services no later than 180 days after the law is enacted. 

• New or expanded research grants on overdose through the National Institute on Drug Abuse (NIDA), which would include a review of current research funding and grants to evaluate existing or trial interventions.

The Drug Policy Alliance has a few more details in their press release. All in all, the bill is an exciting development and just the fact of its existence helps keep momentum going in the right direction with the Feds. OPA encourages American readers to thank their congressional representative if they co-sponsored the bill (there's a list here), and others to call their rep and encourage them to support it.

American Medical Association Endorses Naloxone-Based Overdose Prevention as its Official Policy

By Leo Beletsky, Elena Moroz
Follow Beletsky on Twitter

A Press Release from the American Medical Association on June 19th, 2012 stated the following on AMA’s new policy on community-based programs offering naloxone to prevent opioid overdoses:


PROMOTING PREVENTION OF FATAL OPIOID OVERDOSE: Opioid addiction and prescription drug abuse places a great burden on patients and society, and the number of fatal poisonings involving opioid analgesics more than tripled between 1999 and 2006. Naloxone is a drug that can be used to reverse the effects of opioid overdose. The AMA today adopted policy to support further implementation of community-based programs that offer naloxone and other opioid overdose prevention services. The policy also encourages education of health care workers and opioid users about the use of naloxone in preventing opioid overdose fatalities.

Transcript from FDA Hearing on Naloxone Access Now Available

As previously discussed on OPA, the U.S. Food and Drug Administration (FDA) organized a workshop this past April to examine access to naloxone as a means to reduce opioid overdose fatalities in the Unites States. FDA has now published the complete transcript of the event, available here (PDF). 


We will post choice excerpts in coming weeks, but the entire transcript is worth reviewing and referencing, and includes testimony from leading advocates, researchers, and officials from CDC, FDA and SAMHSA among others. 


One immediate way that advocates may follow up on the workshop is to submit comments on the subject, which FDA is accepting until June 12. Doing so will support efforts to convince FDA to take action on expanding naloxone access, which has included discussion of rescheduling the medication to remove prescription requirements. For information on how to submit comments and suggestions for doing so, follow this link. 

Important! FDA Accepting Public Comments on Naloxone Availability

Last month OPA reported on a U.S. Food and Drug Administration hearing on strategies for improving access to naloxone. FDA is now accepting public comments until noon EST June 12, 2012. The more comments that FDA receives, the more likely our allies in the U.S. federal government will be able to push the issue.


You may submit comments individually or on behalf of an organization through this link, or by going to www.regulations.gov, searching for "naloxone" and clicking the link for "Role of Naloxone in Opioid Overdose Fatality Prevention."


Here are some suggestions sent out today by Harm Reduction Coalition's Whitney Englander:

(1) We need to generate VOLUME to FDA for the docket on the public workshop - numbers matter (2) The messages in the comments should be - as much as possible - to include references to the science, evidence, data, etc. - especially anything in the MMWR, or other data produced or published by government (e.g., NIDA, SAMHSA, FDA, CDC, etc.) (3) Any additional references to information or statements by other groups about the problem of overdose (e.g., data from American Hospital Association) and how naloxone will be a good remedy (4) We should extrapolate the data to illustrate what the "market" could be for naloxone -number of households with prescription opioids, number of American households with children/teenagers, etc.  anything to show that the potential market is bigger than what the industry rep suggested it is (5) Anything regarding economic impact - the cost of overdose - cost of emergency services/emergency department cost of someone who doesn't get emergency services right away and experiences brain damage from lack of oxygen, etc. - show the impact on society and economy (6) Be sure to make clear there is no adverse impact on people who do not have opioids in their system - science to illustrate this and anything regarding lack of side effects or nominal adverse effects - that the benefits FAR outweigh any possible problems with naloxone's use/expanded access.

And a few more guidelines from Maya Doe-Simkins:

On the comment page, fill in the fields and paste your comment of 2000 characters or less. 

All submitted comments are public record, which means that they are publically available, but comments from individuals will not be displayed on the website, unless you specifically request it.

Unless you are representing an organization, select "Individual Consumer" under the "Category" choice. 

You can use 2000 characters for an overview and submit a much lengthier statement as a PDF attachment, including letter on letterhead if available, graphs, figures, published papers, pictures, photos, etc. So, no need to feel constrained to 2000 characters if you have more to say!

Tips for crafting comments that may be helpful in expanding naloxone access:Comments should focus less on IF naloxone works, and more about the pros and cons of giving it to lay overdose bystanders and how simple (or not) that process is/should be. 

These are issues that have the potential to impede expanded naloxone access.  Consider addressing one or more in your comments if you are able:

• Is the training simple?/ Do people feel well prepared to use it?/ If you did use it, could you/the person who used it easily remember instructions?
• Does having naloxone increase drug use or decrease treatment?
• Does having naloxone during an overdose mean that people won’t call 911?
• Any bad outcomes after using naloxone?  Naloxone has a shorter half-life than opioid drugs- has anyone ever re-overdosed after the Narcan wore off?  If yes, what happened?
• Anyone who used naloxone or had it used on them by a lay person may want to mention if it was nasally administered or injected.
• If you are a provider/prevention/public health organization, Has it changed your service delivery?  How much training is necessary? 
• If the price or availability of naloxone has been a concern, please mention this!

Personal experience is powerful if you are comfortable sharing

If you submit comments, please advise Eliza Wheeler (wheeler [at] harmreduction.org) and Alice Bell (abell [at] pppgh.org) of your submission.

Who cares about overdose prosecutions?

by Matt Curtis

We’ve had a lot of good news around overdose lately. The U.S. Centers for Disease Control and Prevention recently released a report on community-based overdose prevention programs, and the Food and Drug Administration just held a hearing on making naloxone more available. The Commission on Narcotic Drugs – the annual social mixer for lifer international drug war bureaucrats – endorsed giving more attention and resources to overdose prevention. It seems like every week there’s more great work being done on the front lines.

One other thing you’ll notice if you keep track of overdose-related news in the United States is the number of criminal prosecutions following overdose deaths.

These prosecutions have their origins in the Narcotics Penalties and Enforcement Act of 1986, also known as the “Len Bias Law” after the star University of Maryland forward who died of cocaine poisoning two days after being drafted by the Boston Celtics. This was the first major federal legislation of the ‘war on drugs’ era, which amended the Controlled Substances Act to introduce mandatory minimum sentences and a number of other enhanced criminal drug penalties.  One novel feature of the law was that it significantly increased prison time for anyone convicted of supplying drugs “if death or serious bodily injury results from the use of such substance.” Though federal prosecutions are still common, many states subsequently adopted similar legislation.

So, fine you say, isn’t this just drug dealers and corrupt pill mill doctors getting what they deserve for poisoning people?  A scan of news articles from the past couple years does show the occasional major dealer going down with a second-degree murder charge tacked on for an overdose. More common is a case like that of April Lynn Baker and Ryan Hartley in Maryland.

In 2008, Ms. Baker acquired methadone and morphine from a nursing home staff, which she traded to Mr. Hartley for marijuana. Hartley then sold a single 40 mg methadone wafer and 20 ml of liquid morphine to Brandon Sgaggero, who was found dead from an apparent overdose five days later. In describing Baker and Hartley as drug dealers, prosecutors note that both used drugs themselves, which is what led Sgaggero to seek out Hartley, and that Hartley sold to Sgaggero on only one occasion. In the event, Baker was sentenced to three years in prison and Hartley six.

Other examples abound, in Tennessee, Wisconsin, Washington and elsewhere. We’ve even seen prosecution of people for not adequately responding to a witnessed overdose, as in this case in Virginia.

The way in which criminal liability for overdose deaths is currently handled is very difficult to square with our rhetoric about harm reduction and drug policy. Yet I have rarely have heard colleagues in harm reduction or the broader public health and medical fields even mention the issue. This may be because the issue presents itself infrequently in the context of harm reduction services, and it’s even less often brought to the attention of people working in policy or academia. For those cognizant of overdose prosecutions, I suspect there’s a degree of ambivalence related to the getting-what-they-deserve issue. Among the many people working in harm reduction now who come from a professional rather than activist background, many may feel that the issue lies outside the scope of public health or social work.

So I think it’s time to take a deeper look at this issue, and it’s time for harm reduction and drug policy reform advocates to take it on. What is the best way to do so is a little more complicated, and something I will address in future posts around some of these questions:

• What is the scope of the problem? Where and how are overdose-related prosecutions happening?
• Should sellers be responsible for outcomes, and if so then under what circumstances? Should the expectation of potential harm from illegal drug use be a legitimate defense?
• How or why should we approach this differently than sellers of other (potentially) adulterated products, like produce contaminated with E. coli or counterfeit medication?
• People who use drugs tend not to keep a log of who they buy from, and medical examiners can’t determine the provenance of a morphine or cocaine metabolite. So is it appropriate to prosecute someone for an act that cannot be forensically linked to the outcome?
• People in drug policy reform often say something akin to ‘No one should be incarcerated for a petty, nonviolent drug crime.’ Where is the line drawn? Who is a drug dealer? Are there any circumstances under which supplying drugs that lead to “death or serious bodily injury" should result in criminal liability, and if so, in the current system is there any way to fairly determine guilt?

I admit some of these questions are a bit loaded. I don’t have the answers figured out though, and welcome comments, counterarguments, data, and anything else you would like to contribute.

FDA Hears Testimony on Naloxone Access and Potential for Over-the-Counter Status

This past Thursday, April 12, the U.S. Food and Drug Administration (FDA) held its first ever workshop on naloxone availability and use in emergency first aid in the United States. The event marks an important first step in the federal government taking greater responsibility for overdose prevention efforts, and by all accounts FDA was looking for ways to be a constructive partner with local peer distribution efforts.  More information on the goals of the meeting, the agenda, and a speakers list may be found on the FDA website. 

While the goal of rescheduling naloxone to remove prescription requirements faces significant bureaucratic hurdles, FDA may be able to take other measures in the near term, such as approving emergency importation of naloxone from manufacturers in Europe or elsewhere in order to address the stock-outs and price hikes plaguing overdose projects in recent years.

We'll soon have more analysis about the meeting and next steps from several participants. In the meantime, Time magazine's Maia Szalavits continues her quest to make completely OPA redundant with an excellent first-take on the meeting.