Press release: Naloxone cost-effective

City and County of San Francisco Edwin M. Lee Mayor

San Francisco Department of Public Health Barbara A. Garcia, MPA Director of Health

Embargoed until 5p.m. Eastern Time	Eileen Shields, Public Information Officer
December 31, 2012	415/554-2507 (o) 415/370-3377 (cell) Eileen.Shields@sfdph.org

Study Shows Naloxone Cost-Effective in Preventing Overdose Deaths

San Francisco, CA, January 1, 2013 - The Annals of Internal Medicine released a study this week demonstrating that giving heroin users the overdose antidote naloxone is a cost-effective way to prevent overdose death and save lives. Phillip Coffin, MD, Director of Substance Use Research at the San Francisco Department of Public Health and Assistant Clinical Professor at the University of California San Francisco, and Sean Sullivan, PhD, Professor and Director of the Pharmaceutical Outcomes Research and Policy Program at the University of Washington, co-authored the study.

Drug overdose is now the leading cause of injury death in the United States with opioids, such as heroin, accounting for about 80% of those deaths. Naloxone is a safe and effective antidote that works by temporarily blocking opioid receptors. As of 2010, 183 public health programs around the country, including those supported by the San Francisco Department of Public Health, had trained over 53,000 individuals in how to use naloxone. These programs had documented more than 10,000 cases of successful overdose reversals.

The authors of this study developed a mathematical model to estimate the impact of distributing naloxone in this way. Their model was based on conservative estimates of the number of overdoses that occur each year. It accounted for people who overdose repeatedly, and it acknowledged that most people who overdose will survive whether or not they get naloxone.

In their basic model, Coffin and Sullivan estimated that reaching 20% of a million heroin users with naloxone would prevent about 9,000 overdose deaths over their lifetime. One life would be saved for every 164 naloxone kits given out. Based on optimistic assumptions, naloxone could prevent as many as 43,000 deaths – one life for every 36 kits given out.

Naloxone distribution would cost about $400 for every quality-adjusted year of life gained. This value is well below the customary $50,000 cutoff for medical interventions. It is also cheaper than most well-accepted prevention programs in medicine – most similar to the cost-effectiveness of smoking cessation or checking blood pressure. All reasonable assumptions produced costs that were well within traditional guidelines for cost-effectiveness.

“Naloxone is a highly cost-effective way to prevent overdose deaths,” said Dr Coffin. “And, as a researcher at the Department of Public Health, my priority is maximizing our resources to help improve the health of the community.”

Naloxone distribution has existed in San Francisco since the late 1990s, with SFDPH support since 2004. During that time, heroin overdose fatalities slowly decreased from a peak of 155 in 1995 to 10 in 2010. Opioid analgesic deaths (e.g., oxycodone, methadone, or hydrocodone) remain elevated, with 121 deaths in 2010. Efforts are currently underway to expand access to this lifesaving medication for patients receiving prescription opioids as well.

Contact Information and Follow-up

To obtain a copy of this study, see Annals of Internal Medicine

To discuss the paper, contact Dr. Coffin, pcoffin@gmail.com

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More OD videos - Cops, reentry, and Spanish OD training!

It seems like there are a bunch of good overdose advocacy and training videos coming out these days. 

Here's a new video from the San Francisco Police Department and Department of Public Health instructing police not to interfere with syringe access sites or naloxone distribution. (Nice narration Emalie Huriaux!)




And here's a new Spanish-language video from Boston about how to recognize overdose and respond properly. The video highlights the fact that those just released from prison or other lock-up facilities are at higher risk of OD, especially in those first two weeks.

And while we're at it, we realized that OPA didn't mention the great video, "Staying Alive on the Outside" from our friends in Rhode Island that came out a few months back. It's and English-language video that focuses on OD risk and response after prison release. 



We hope you find these useful in your work!

Quote of the Day

"The naloxone shortage is going to hurt us. It is hurting us. People are dying now because of the shortage. More people are going to die because of it. Whatever your story is, you shouldn't have to die for how you choose to navigate your life and what's happened to you. We need naloxone everywhere. Opioid users didn't just appear out of nowhere -- everybody has someone that loves them, a father, a mother, a grandparent, a friend, niece, nephew, brother sister ... and you're important to that person. Naloxone can keep them from dying. It's harm reduction on a really intimate, yet grand scale because every OD death that is prevented means hundreds if not thousands of people prevented from losing and grieving."

                ---------- Lee Hertel, Minneapolis USA

A North Carolina family talks about overdose

Shelly's Story from North Carolina Harm Reduction on Vimeo.

PubMed Update October/November 2012

My apologies for tardiness. I'll try to be on time next month. 13 papers described below.

1. Prevention of fatal opioid overdose.

Beletsky L, Rich JD, Walley AY.

JAMA. 2012 Nov 14;308(18):1863-4. doi: 10.1001/jama.2012.14205.

Comment: An excellent summary of key issues in overdose prevention and increasing naloxone availability for lay overdose reversal. Read it.

2. Management of opioid analgesic overdose.

Picetti E, Rossi I, Caspani ML.

N Engl J Med. 2012 Oct 4;367(14):1371-3

Comment: Multiple letters in response to the recent review article.

3. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence.

Krupitsky E, Zvartau E, Blokhina E, Verbitskaya E, Wahlgren V, Tsoy-Podosenin M, Bushara N, Burakov A, Masalov D, Romanova T, Tyurina A, Palatkin V, Slavina T, Pecoraro A, Woody GE.

Arch Gen Psychiatry. 2012 Sep;69(9):973-81.

Comment: This was a randomized, placebo-controlled trial comparing naltrexone implant to oral naltrexone to nothing for preventing relapse to opioid dependence among detoxified patients in Russia. Participants were followed for six months and then followed up a year later to see if there was more death from overdose. The implant was more effective in retaining participants through the six months although by 3 months off therapy there was no difference between the groups. Authors only report “no evidence of increased risk of death due to overdose after  naltrexone treatment” and cite the initial paper showing injectable naltrexone as effective for opioid dependence in Russia (I’m unclear as to why this citation was present). I find this radically insufficient. Naltrexone has lab evidence (animal evidence shows that exposing opioid receptors to naltrexone makes them more sensitive to opioids than mere abstinence) and clinical evidence (high death rates after oral naltrexone treatment) suggesting that it increases risk of overdose and overdose death. The authors of this paper provide no details as to how they showed no evidence of increased overdose. How many people were they able to follow-up with at 18 months (their numbers were really small to begin with)? Did they inquire as to non-fatal overdose? How did they collect information about overdose death (coroners in Russia rarely identify overdose as a cause of death due to stigma and payment issues)? While extended-release naltrexone formulations *might* have less of an association with overdose, the concerns about oral naltrexone are well-established - how did the investigators get approval for oral naltrexone for opioid users from a U.S. government funded study? This is a vulnerable population for whom greater attention to toxicities should be demanded. A high level of attention to overdose outcomes might put to rest these concerns, but I have not seen that as of yet.

NCHRC OD films

The North Carolina Harm Reduction Coalition has been busy making short films about overdose. Check out these two new ones:

Harm reductionists talk about overdose:


Current and former drug users talk about overdose:

Coming to the Harm Reduction Conference? Help us Make a Movie About Naloxone Access

The biennial U.S. National Harm Reduction Conference takes place in Portland, Oregon this week, and a group of us have formed up to produce a short documentary film about how recent increases in the cost of naloxone and production shortages have impacted community-based overdose prevention projects. The film will be used in advocacy with the manufacturers and with local, state and federal agencies to improve access to naloxone. 

If you'll be in Portland and work on overdose prevention, we need your help.  Here's how DOPE Project's Eliza Wheeler describes it:

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.

PubMed Update September 2012

Another busy month in overdose-related research (11 papers), including several toxicology and epidemiology papers, some of which represent novel analytic approaches that serve to advance the field.

1. Oxycodone overdose causes naloxone responsive coma and QT prolongation.

Berling I, Whyte IM, Isbister GK.

QJM. 2012 Sep 28. [Epub ahead of print]

PMID: 23023890 [PubMed - as supplied by publisher]

Comment: High-dose opioids can cause QT prolongation, a hypothetical bugaboo for methadone maintenance. What is QT prolongation? It is a warning sign that somebody might be at risk for a potentially fatal heart rhythm. More detail, you ask? Well, the EKG is a record of electrical activity in the heart – see below. Some medications make the time from Q to T longer. If it gets long enough (usually requiring very high doses of opioids in combination with either other medications or a genetic tendency to have a long QT) it can result in a dangerous heart rhythm. 

2. Factors associated with mortality among heroin users after seeking treatment with methadone: A population-based cohort study in Taiwan.

Huang CL, Chung-Wei L.

J Subst Abuse Treat. 2012 Sep 25. pii: S0740-5472(12)00138-9. doi: 10.1016/j.jsat.2012.08.003. [Epub ahead of print] 

Comment: Methadone is protective from death, but there still is quite a bit of mortality, including overdose.

3. Delayed posthypoxic leukoencephalopathy: Case reports.

Okuda S, Ueno M, Hayakawa M, Araki M, Kanda F, Takano S.

Rinsho Shinkeigaku. 2012;52(9):672-6. 

Comment: Two case reports of a debilitating white matter brain disease from benzodiazepine overdose.

4. The relationship between alcohol use and injecting drug use: Impacts on health, crime and wellbeing.

Dietze P, Jenkinson R, Aitken C, Stoové M, Jolley D, Hickman M, Kerr T.

Drug Alcohol Depend. 2012 Sep 15. pii: S0376-8716(12)00330-4. doi: 10.1016/j.drugalcdep.2012.08.013. [Epub ahead of print]

Comment: Drug injectors who drink heavily have more violent crime and poorer life satisfaction. Somewhat surprisingly, other health outcomes (like heroin overdose) did not survive controlling for potential confounders.

India Takes Up Overdose Prevention

by Nandini Pillai

Manipur, in Northeast India, has long battled an injection driven HIV epidemic, but took early steps to address it.  The state was among the first places in the country to adopt harm reduction measures, first "bleach and teach” programs before needle and syringe programs (NSPs) were considered acceptable, and then NSPs starting in 1994.  Manipuris were among the first to accept OST and run community based OST programs (1999-2002 and then again in 2006 continuing today).  Manipur was the first state in India to develop an HIV policy based in harm reduction principles in 1996, a policy that was later used as the basis of the national AIDS policy.  

Despite this forward thinking, naloxone isn’t currently available in state funded drop-in centers (DICs).  It is available for purchase in pharmacies in the cities, but it is often inaccessible because pharmacists know that people only buy naloxone in emergency situations and inflate the prices, sometimes to as much as 3000 rupees (about USD 50). In a place where harm reduction has been embraced for decades, it is sad to see that overdose prevention hasn’t been more of a priority.  

The good news is overdose awareness and advocacy for naloxone availability is on the agenda.  NGOs operating under Project ORCHID, the Bill & Melinda Gates funded HIV prevention program in Manipur and Nagaland, have stocked naloxone in DICs and trained staff to promote overdose awareness since 2009.  The Northeast India Knowledge Network Project has documented this program in a new publication, In Time: Drug overdose management in Manipur and Nagaland.    

The success of this program, as well as advocacy efforts from user groups and other service providers have helped to highlight overdose awareness at state and national levels.  The two main hospitals in Imphal now stock naloxone in their emergency departments, so patients' friends or relatives no longer have to negotiate with pharmacists outside the hospital.  Recently, the National AIDS Control Program included overdose management in their plans, meaning that even state funded DICs will stock naloxone.  Once integrated into government funded DICs, overdose will also be tracked as part of the central information management system which I hope will help us better understand overdose trends, and respond to them more effectively.

For more information about HIV prevention programs in Northeast India, please visit the Northeast India Knowledge Network webpage.

Nandini Pillai is a Project Officer with the Australian International Health Institute in New Delhi, India.

Policy: Overdose Legislation

The Network for Public Health Law has developed an excellent summary of naloxone access and Good Samaritan legislation in the United States. The authors have generated a helpful table to explain the confusing range of protections offered by the distinct language in each law

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 …

EPIDEMIOLOGY

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.

2) Characteristics of drug users who witness many overdoses: Implications for overdose prevention.

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.

3) Drug-Related Death Following Release from Prison: A Brief Review of the Literature with Recommendations for Practice.

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.

4) Mortality among Substance-using Mothers in California: A 10-year Prospective Study.

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).

5) An analysis of the root causes for opioid-related overdose deaths in the United States.

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.

Pubmed Update August 2012

Just one paper to talk about, but I think it warrants discussion.

Aversive and reinforcing opioid effects: a pharmacogenomic twin study.

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.

I take two messages from this paper:

1) We've known for years that people who overdose are highly likely to overdose again, but we don't understand all of the reasons why. Is it behavioral (e.g. polydrug use, short stints of abstinence) or physiologic (e.g. lung disease, liver disease, etc)? Now we know that part of the reason is genetic.

2) While I still suspect there are ways to reduce the risk of overdose by changing patterns of drug use, some of that risk is genetic and unlikely to be affected by education.