Understanding Contributors to US Drug-Related Mortality

Much has been written in public press about claimed relationships between clinical prescribing of opioid pain relievers and a so-called “prescription opioid crisis” in the US.  There is conclusive proof, based on data collected by US Centers for Disease Control and Prevention (CDC), that for over 10 years there has been no relationship between rates of opioid prescribing and either hospitalizations for opioid toxicity or deaths in which a prescription opioid is a contributing factor. ^[1] The CDC has also asserted that every patient treated for severe pain with prescription opioids is at immediate risk of addiction — another assertion that has been definitively disproven ^{[2], [3]} . These realities have not kept the CDC from continuing to claim that doctors are responsible for the opioid crisis in their past and persistent opioid “over-prescribing.”

A landmark paper published in 2018 ^[2] casts a very bright light on these assertions and demonstrates beyond any reasonable contradiction that CDC claims are fundamentally in error.  To understand the real contributors to US drug-related mortality, it is important to examine mortality data in detail.

Figure 1:  US Accidental Mortality from Individual Drugs and from All Drugs, 1999 to 2016 (deaths per hundred thousand population)

Jalal, et al analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System, in which accidental drug poisoning was identified as the primary cause of death.  By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, they provided “evidence that the [then-] current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process.”

Mortality data in Figure 1 are from the original paper. The Figure informs us that prescription opioid analgesics are only one of eight contributing factors in the exponentially rising accidental mortality associated with all drugs from 1980 to 2016 and beyond.  

Specifically:

1.    Accidental drug-related mortality rates overall rose exponentially from 1980 to 2016.  The sum of eight contributors to mortality is closely aligned to the aggregate curve after 1999.

2.    Unspecified narcotics and drugs of unknown type were estimated to contribute 3.6 out of 17 deaths per hundred thousand in 2016 – 21% of all accidental deaths involving drugs of any kind.  This fraction varies only in a narrow range from 1999 to 2016 and is an outgrowth of reporting uncertainty among County Medical Examiners and Coroners.  Uncertainty in cause of death also reflects the presence of multiple toxic substances in many deaths, including alcohol which is not tracked in the Figure.

3.    “Prescription drugs” comprise an aggregate of two components:

a.    Drugs legitimately prescribed by clinicians to their patients, and

b.    Prior to 2012, prescriptions dispensed from pill mills to street resellers for non-medical use.

The proportion of prescription drug deaths that should be attributed to legitimate versus diversionary prescribing is not definitively known.  However from 2010 to 2016, sales of prescription drugs dropped by 25% even as all drug-related mortality increased by 70%, suggesting that neither valid nor diverted prescriptions never dominated overall mortality.  Other sources have noted that prescription drug sales continued to drop significantly from 2016 to 2020, as non-prescription drug-related mortality continued to soar.^[4]  Thus it seems clear that opioids prescribed to patients by conscientious practitioners did not “cause” the widely discussed US opioid “epidemic” in this period.

4.    Concurrent with closures of illegal pill mills in 2010 to 2012, a 2-year dip occurred in mortality rates attributed to prescription drugs.  Thereafter, mortality associated with prescription drugs continued to move upward for complex reasons, but still remained at less than a quarter of total accidental drug mortality.

5.    Following the US-mandated reformulation of Oxycodone to abuse-resistant form in 2010, deaths attributed to heroin exploded by 400% from 2010 to 2016.  Deaths attributed to synthetic opioids other than methadone (primarily illegal fentanyl) increased by over 600%.

A plausible explanation for combined drug-related mortality after 2010 is that both medical and non-medical users of pharmaceutical grade drugs were driven into unsafe street markets by restrictions on availability of much safer pharmaceutical opioids.  Forced dose tapering of clinical patients may also have contributed to deaths by medical collapse and suicide,^[4] mischaracterized as “accidental” death.

Fundamental Causes of Illicit Drug Deaths and Mortality

There are now extensive data that solidly link illicit drug use to loss of community institutions, loss of jobs and persistent unemployment, physical disability, often with pain, breakup of families, poor mental health, hopelessness, and ultimately lives of desperation and despair. These factors have particularly affected people with less than a college education, and even more so, people with less than a high school education.

A Legal Issue for the DEA

The data portrayed in Figure 1 are important in the present context for a larger reason than the contradiction they offer to the now-ubiquitous false memes generated by the CDC and the misdirection this organization has caused in public health policy. The US Drug Enforcement Administration has also known of these data for the past four years.

Figure 1 was published in a DEA Diversion Control Division conference in February 2020 ^[7]  However, this knowledge hasn’t kept the DEA from aggressively pursuing and prosecuting clinicians who prescribe opioids to their patients, under the disproven CDC assumption that prescribing is responsible for the US opioid crisis.  The anti-opioid testimony of so-called “expert witnesses” employed by DEA to convict pain doctors is directly contradicted by data of which the DEA was fully aware.  The unscientific DEA position has provided the basis for prosecuting clinicians, only some of whom have successfully appealed their convictions on grounds of malicious prosecution.

References

1. Aubry L and Carr BT, “Overdose, opioid treatment admissions and prescription opioid pain reliever relationships: United States, 2010–2019” , Frontiers in Pain Medicine, Augusts 4, 2022, https://www.frontiersin.org/articles/10.3389/fpain.2022.884674/full
2. Brat GA, Agniel D, Beam A, Yorkgitis B, Bicket M, Homer M, et al. Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study. (2018) 360:j5790. doi: 10.1136/bmj.j5790
3. Sun EC, Darnall BD, Baker E, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. (2016) 176:1286– 93. doi: 10.1001/jamainternmed.2016.3298
4. Jalal J, Buchanach JM, Roberts MS, Balmert :C, Zhang K, and Burke DS, “Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016” Science, Vol 361,  Issue 6408, 21 September 2018, https://www.science.org/doi/10.1126/science.aau1184
5. Op Cit, Aubry and Carr
6. Hemphill, N, “ Forced tapering may harm patients with chronic pain on opioids”. Healio News, Psychiatry, September 9, 2022, https://www.healio.com/news/psychiatry/20220909/forced-tapering-may-harm-patients-with-chronic-pain-on-opioids
7. Guzman, AR, “Drugs of Abuse and Trends”, Practitioner Diversion Awareness Conference, US DEA and Federation of State Medical Boards, February 22-23, 2020, https://www.deadiversion.usdoj.gov/mtgs/pract_awareness/conf_2020/feb_2020/guzman.pdf