PubMed Update November 2014 - February 2015

Catching up on 51 papers in 4 months. Did you miss me?

1) New Drugs of Abuse.

Rech MA, Donahey E, Cappiello Dziedzic JM, Oh L, Greenhalgh E.

Pharmacotherapy. 2014 Dec 4. doi: 10.1002/phar.1522. [Epub ahead of print]

Comment: Review of management of drug toxicities among novel, synthetic compounds.

2) Police officer attitudes towards intranasal naloxone training.

Ray B, O'Donnell D, Kahre K.

Drug Alcohol Depend. 2015 Jan 1;146:107-10. doi: 10.1016/j.drugalcdep.2014.10.026. Epub 2014 Nov 8.

Comment: Police officers like being trained to carry naloxone.

3) Intranasal naloxone administration for treatment of opioid overdose.

Robinson A, Wermeling DP.

Am J Health Syst Pharm. 2014 Dec 15;71(24):2129-35. doi: 10.2146/ajhp130798.

Comment: Review of intranasal naloxone for overdose reversal.

4) Observed transition from opioid analgesic deaths toward heroin.

Dasgupta N, Creppage K, Austin A, Ringwalt C, Sanford C, Proescholdbell SK.

Drug Alcohol Depend. 2014 Dec 1;145:238-41. doi: 10.1016/j.drugalcdep.2014.10.005. Epub 2014 Oct 18.

Comment: Heroin overdoses are increasing.

5) Brief overdose education can significantly increase accurate recognition of opioid overdose amongheroin users.

Jones JD, Roux P, Stancliff S, Matthews W, Comer SD.

Int J Drug Policy. 2014 Jan;25(1):166-70. doi: 10.1016/j.drugpo.2013.05.006. Epub 2013 Jun 15.

Comment: Brief overdose training works for naloxone distribution. This is important because many places are requiring prolonged trainings that end up limiting access to those who are unable or unwilling to invest that degree of time.

6) Brief overdose education is sufficient for naloxone distribution to opioid users.

Behar E, Santos GM, Wheeler E, Rowe C, Coffin PO.

Drug Alcohol Depend. 2015 Mar 1;148:209-12. doi: 10.1016/j.drugalcdep.2014.12.009. Epub 2014 Dec 19.

Comment: Again, brief overdose training works for naloxone distribution.

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.

At your service: Overdose Q&A from the Thai national overdose training

The Thai AIDS Treatment Action Group (TTAG) recently organized a national overdose training for harm reduction groups in Thailand. Participants raised a number of questions about overdose, some of which were passed on to me by TTAG’s Karyn Kaplan. We thought it made for a nice Q&A, and so we share the results below.  ---Matt Curtis

Karyn Kaplan: There was definitely confusion about the role of CPR in a heroin OD, or a poly-drug OD. They got the breathing-is-essential thing, but does one STOP the breathing to administer CPR and when? Or, never with heroin OD, just do rescue breathing?

Matt and Karyn on the Chao Phraya River in Bangkok

Matt Curtis: The point is that you don't want to do chest compressions on someone who's heart is still doing its job, which will be the case in most heroin/opioid or benzo overdoses. Opioids don't cause the heart to stop; in this case an extended period of oxygen deprivation causes the heart to stop, at which point chest compressions are indicated, but probably not going to help much.

In treating an opioid OD, it's best to focus on airway management, breathing, and naloxone, and even better to do all that plus get the person professional medical attention. I’d say it’s also especially important to focus in on this point in our OD prevention work, like when delivering a short (e.g. 5-10 min) training in a harm reduction setting. If there's time, it's always appropriate to teach people to check the ulnar (wrist) and jugular (neck) pulse, but again I'd stress oxygen always + naloxone if available.

Also, a small nomenclature issue: CPR = rescue breathing + chest compressions, which isn't really the normal recommended standard of care for any situation anymore – see for example the American Heart Association guidelines on rapid chest compression for heart failure, which the Harm Reduction Coalition has nicely summarized specifically in relation to overdose.  

KK: Once naloxone wears off, can you OD again from any residual heroin? There was this question about heroin still being in your body.

MC: Yes. Heroin continues to be metabolized while naloxone is active, but naloxone does not remove heroin from the body. This is why people will generally stop feeling dopesick and potentially high again as naloxone starts wearing off after 30 minutes or so. Although there is risk of OD’ing again after naloxone is administered – and certainly a much greater risk of OD if people use again soon after being revived – in practice this seems to be very rare.

A typical example is from a 2006 paper published out of the Chicago Recovery Alliance overdose project. Among 319 documented overdose reversals with naloxone there were NO cases of re-treatment being needed after the initial dose of naloxone wore off.  And for that matter, there were only five cases where more than one dose of naloxone was needed, two cases of non-withdrawal complications (1 vomiting, 1 seizure), and only one death. Other studies, including ones that have looked for deaths after people were discharged from hospital emergency departments after treatment for heroin overdose, have confirmed the Chicago findings.

All that said, it’s important to promote aftercare, because the risk of going back into OD is real, because there can be other complications of nonfatal overdose, and because it’s just good to take care of people.

Getting naloxone into the hands of people who use drugs in Thailand

by Karyn Kaplan, Thai AIDS Treatment Action Group (TTAG)

“Is it legal?” “What if you inject it in a vein?” “Does it work on a benzo OD?” ”Can you buy it in a pharmacy?” “Does it lead to more drug use?”

These were some of the many questions about naloxone posed by 40 harm reduction project staff and people who inject drugs (PWID) from 14 drop-in centers and NGOs across Thailand, at our first National Overdose Prevention and Management TOT in Bangkok (July 13-14, 2011). We had just distributed over 800 doses to the participants, along w/3mL syringes and 24G/1” needles. Most of them had never seen, let alone heard of, this miraculous drug.

Thailand, despite having roughly 50% IDU HIV prevalence for the past 20 years (HCV prevalence is even higher), does not embrace harm reduction, has no official policy to support it, and has just started “piloting” evidence-based HIV prevention interventions for PWID with Round 8 Global Fund money. Given that Thailand has known only violent government-endorsed drug crackdowns and stigmatizing anti-drug campaigns, it is no wonder our trainees were concerned about being seen as “promoting drug use” or being arrested for implementing a pioneering intervention that promotes the health and rights of people who use drugs.