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.

4. Transdermal fentanyl in deliberate overdose in pediatrics.

Lyttle MD, Verma S, Isaac R.

Pediatr Emerg Care. 2012 May;28(5):463-4.

Comment: A suicide attempt by multiple fentanyl patches, successfully treated with naloxone infusion and inpatient psychiatric care.

5. Understanding drug-related mortality in released prisoners: a review of national coronial records.

Andrews JY, Kinner SA.

BMC Public Health. 2012 Apr 4;12:270. doi: 10.1186/1471-2458-12-270. Review.

Comment: Almost half of the deaths among ex-prisoners in Australia from 2000-2007 were due to drug overdose, 82% of which demonstrated heroin and/or morphine on toxicology. Those who died of drug-related death were less likely that those who died of other causes to have mental health conditions or a history of self-harm. The were more likely to have a history of heroin use, drug withdrawal, injecting drugs, and drug overdose.

6. Staff concerns in heroin-assisted treatment centres.

Demaret I, Lemaître A, Ansseau M.

J Psychiatr Ment Health Nurs. 2012 Aug;19(6):563-7.

Comment: Avoiding overdose is a significant concern for staff at heroin treatment programs. As those who had used benzodiazepines or cocaine have been more likely to overdose in the program, nurses have managed this concern in part by assessing the level of intoxication prior to providing heroin.

8. [Opiates, harm reduction and polysubstance abuse.]

Touzeau D, Courty P.

Presse Med. 2012 Oct 31. doi:pii: S0755-4982(12)00524-6. 10.1016/j.lpm.2012.07.038. [Epub ahead of print] French.

Comment: A review of opioids and harm reduction in French, which I cannot read.

9. Unintentional Prescription Opioid-Related Overdose Deaths: Description of Decedents by Next of Kin or Best Contact, Utah, 2008-2009.

Johnson EM, Lanier WA, Merrill RM, Crook J, Porucznik CA, Rolfs RT, Sauer B.

J Gen Intern Med. 2012 Oct 16. [Epub ahead of print]

Comment: The authors interviewed next of kin or best contacts, a very compelling approach to studying the characteristics of opioid analgesic use resulting in overdose death. About a quarter had a history of heroin use and the vast majority had been to the emergency department previously for problems related to substance use. Over 90% had gotten prescription pain medication from a healthcare provider within the year leading up to their death (prescription database studies have suggested one to two-thirds of deaths are due to drugs prescribed to the decedent, but getting some prescriptions from a healthcare provider does not necessarily mean they received the agent that led to the overdose from a provider).

10. Adverse effects associated with non-opioid and opioid treatment in patients with chronic pain.

Labianca R, Sarzi-Puttini P, Zuccaro SM, Cherubino P, Vellucci R, Fornasari D.

Clin Drug Investig. 2012 Feb 22;32 Suppl 1:53-63.
Comment: A review of side effects of multiple different pharmacotherapies for pain.

11. A Review of Potential Adverse Effects of Long-Term Opioid Therapy: A Practitioner's Guide.

Baldini A, Von Korff M, Lin EH.

Prim Care Companion CNS Disord. 2012;14(3).

Comment: I particularly appreciate the authors’ effort to put some numbers behind opioid analgesic overdose. Based on two prior papers, they state that the rate of overdose among high-dose opioid analgesic users is 1.8% and that 12% of overdoses are fatal, suggesting a death rate of 2 per 1,000 person years of high-dose opioid prescription. I would love to see other analyses with consistent results, but this is certainly a place to start. To put this in context, among heroin users, around 20% overdose in a given year and around 5% of overdoses are fatal.

12. Cognitive skills underlying driving in patients discharged following self-poisoning with central nervous system depressant drugs.

Dassanayake TL, Michie PT, Jones AL, Mallard T, Whyte IM, Carter GL.

Traffic Inj Prev. 2012 Sep;13(5):450-7.

Comment: Interesting paper exploring the persistent impairment in cognitive functioning after drug poisoning. The authors focused on possible residual drug effect, although I do wonder if there is a cognitive impact of non-fatal overdose beyond residual drug effect.

13. Death Due to Apparent Intravenous Injection of Tapentadol.

Kemp W, Schlueter S, Smalley E.

J Forensic Sci. 2012 Oct 19. doi: 10.1111/j.1556-4029.2012.02299.x. [Epub ahead of print]

Comment: Tapentadol is opioid available by the brand names Nucynta and Palexia.