Fentanyl and opioid deaths

There is a current report in MMWR highlighting the increasing numbers of opioid deaths and the role of fentanyl and its analogs (see https://www.cdc.gov/mmwr/volumes/66/wr/mm6643e1.htm ).

Details:

--US drug overdose deaths exceeded 60,000 in 2016, partially from synthetic opioid deaths (excluding methadone), which have increased five-fold over the past 3 years: from 3,105 in 2013 to approximately 20,000 in 2016.

--this report describes opioid overdose deaths during July–December 2016 in 10 states participating in CDC's Enhanced State Opioid Overdose Surveillance (ESOOS) program: Oklahoma, New Mexico, Wisconsin, West Virginia, Ohio, Maine, Missouri, Rhode Island, Massachusetts, New Hampshire

Results:

--Fentanyl was detected in 56.3% of 5152 opioid overdose deaths in the 10 ESOOS states and was judged to be the cause of death in 97.1% of the cases

--Approximately 90% of opioid deaths in New Hampshire were associated with fentanyl, 75% in Massachusetts, 70% in Rhode Island, 55% in Ohio, Maine, Missouri, and 50% in West Virginia

--States detecting any fentanyl analogs in >10% of opioid overdose deaths were spread across the Northeast (Maine, 28.6%, New Hampshire, 12.2%), Midwest (Ohio, 26.0%), and South (West Virginia, 20.1%), with carfentanil, furanylfentanyl, and acetylfentanyl identified most frequently.

--Fentanyl analogs were present in 720 (14.0%) opioid overdose deaths, with the most common being carfentanil (389 deaths, 7.6%), furanylfentanyl (182, 3.5%), and acetylfentanyl (147, 2.9%)

--Demographics of fentanyl and fentanyl analog deaths: mostly 25-44yo (median age 38), 72% male, 83% "non-Hispanic White"

--Most fentanyl deaths included more than one fentanyl: 0.9%, 51.1%, and 97.3% of deaths involving carfentanil, furanylfentanyl, and acetylfentanyl, respectively, tested positive for fentanyl or additional fentanyl analogs.

--Other illicit drugs co-occurred in 57.0% of deaths involving fentanyl, mostly heroin (39%) and cocaine (34.8%); and 51.3% involving fentanyl analogs, also mostly heroin (34.7%) and cocaine (28.1%)

--use of transdermal fentanyl (the legal outpatient one) was rare: 1.2% of fentanyl deaths.

Commentary:

--Fentanyl, a synthetic opioid largely illicitly manufactured and typically mixed with many other illicit drugs (see blogs below), is 50–100 times more potent than morphine, and is primarily responsible for the rapid increase in opioid deaths

--fentanyl analogs such as acetylfentanyl, furanylfentanyl, and carfentanil are being detected increasingly in overdose deaths (these are similar in chemical structure to fentanyl but not routinely detected because specialized toxicology testing is required: ie these numbers of deaths above attributed to the analogs may actually be low, given some areas do not test for all of these analogs):

    --Carfentanil, used to sedate large animals, is estimated to be 10,000 times more potent than morphine. This analog led to 354 overdose deaths in Ohio and 35 in West Virginia. and there are new reports of about 10 deaths in Kentucky and another 10 in New Hampshire

    --acetylfentanyl and furanylfentanyl potencies vary but are probably less potent than fentanyl (illicit fentanyl analog potency has not been evaluated in humans).

-- illicitly manufactured fentanyl (largely from China) is a key factor driving opioid overdose deaths, and this continues to be primarily in states east of the Mississippi River

-- Over half the patients with overdose deaths involving fentanyl and fentanyl analogs tested positive for confirmed or suspected heroin (the most commonly detected illicit substance), cocaine, or methamphetamine. This report confirms prior findings that fentanyl and fentanyl analogs are commonly used with or mixed with heroin or cocaine (in this study, deaths from fentanyl or analogs mixed with cocaine was almost as common as being mixed with heroin)

-- But, about half of overdose deaths involving fentanyl and fentanyl analogs did not test positive for other illicit opioids, suggesting that fentanyl and fentanyl analogs might be emerging as unique illicit products.

--because of the above opioid deaths, the CDC in 2017 increased ESOOS from 10 to 32 states and the District of Columbia, and added funding to improve toxicology testing for fentanyl analogs

so, this report brings up several very concerning issues:

--there is a pretty rapid increase in deaths from fentanyl and its analogs, spreading to different states, and especially with the extremely potent carfentanil.  It is striking both that more fentanyl and analogs seem to be used more often by themselves, without being cut with heroin, cocaine, metamphetamines, etc, and that these fentanyl products are being coformulated with other fentanyl derivatives

--these fentanyl and analog drugs can require multiple doses of naloxone to reverse: ie, it is important that family members trained in delivering naloxone understand that there may need to be more than 1 dose of naloxone to reverse the potentially mortal effects of fentanyl/analogs

--it is important to make sure that the lab you use for tox screens covers both the natural (eg heroin) and synthetic opioids (eg fentanyl), and that they are testing for the fentanyl analogs (especially as the use of these analogs increase in your areas)​

--one tragic irony in the current situation is that we are seeing more patients who developed opioid use disorder after taking pharmaceutical opioids after surgery/ER visits/etc, then buying pills in the streets, then switching to heroin because the pills cost too much, then the heroin is cut with highly potent and very cheap illicit fentanyl (and now its analogs), feeding into the surging opioid death rate...

http://gmodestmedblogs.blogspot.com/2017/08/the-real-opioid-emergency.html which highlights a NY Times editorial noting the very strong racist bias in framing and punishing those with opioid use disorders

http://gmodestmedblogs.blogspot.com/2016/03/new-cdc-guidelines-for-opiate.html​ a review and critique of the new CDC guidelines on opiate prescribing, as well as referring to other prior blogs on the highly addictive potential of prescribed opiates in teens, the unclear benefit of opiates for low back pain, and some of the genetic variants in opioid effects (eg of the mu receptor) and its reflection in individuals' drug use

http://gmodestmedblogs.blogspot.com/2017/07/decreasing-opiate-prescriptions.html noting decreases in current opiate prescriptions

http://gmodestmedblogs.blogspot.com/2017/02/opiate-prescribing-in-elderly-and.html noting that elderly patients seeing clinicians who are high-opiate prescribers tend to continue being on opiates, vs those with similar conditions seeing low-opiate prescribers

http://gmodestmedblogs.blogspot.com/2016/05/2-cdc-reports-on-spread-and-toxicity-of.html for 2 prior CDC reports on the spread and toxicity of fentanyl​