Why Do Opioid Overdose Deaths Continue to Rise?

The most recent data on fatalities from the opioid overdose crisis are for the year 2017, published in MMWR on January 4, 2019. They show that while overdose deaths from both prescription opioids and heroin remained stable during 2016-2017, there was a significant increase in overdose deaths due to synthetic opioids. In this post, I share a few thoughts on the evolving pattern of opioid overdose deaths.

DSM-5 defines opioid use disorder (OUD) as a problematic pattern of opioid use characterized by loss of control of opioid use, risky opioid use, impaired social functioning, tolerance, and withdrawal. Opioid addiction is the most extreme form of OUD, generally associated with severe OUD. More than 2.1 million Americans have an OUD, including 626,000 with heroin related OUD. According to a recent MMWR, 47,600 Americans died of opioid overdoses in 2017, which amounts to an average of 130 individuals each day. This is a 12% increase over 2016 when approximately 116 individuals died on average each day. Synthetic opioids, primarily illicitly manufactured fentanyl and fentanyl analogs were involved in about 60% of opioid overdose deaths, an increase of about 45% from the previous year. Overdose deaths from prescription opioids and heroin remained stable during 2016-2017.

Stabilization of prescription opioid overdose deaths may be due to improved diversion control and the introduction of abuse deterrent (or tamper resistant) dosage forms. There is now compelling evidence that oral prescription opioid abuse by non-oral routes more than doubles the risk of death or life-threatening events. Furthermore, a changeover to abuse deterrent formulations can reduce the extent of tampering and diversion into illicit distribution channels. For example, following the introduction of abuse deterrent OxyContin®, the desirability of OxyContin among persons with OUD decreased dramatically. The rate of intentional abuse, diversion, entry into opioid treatment programs, oral abuse and non-oral abuse declined by 62%, 86%, 73%, 71% and 87%, respectively, and the geometric mean street price decreased by 41%. Presently, abuse-deterrent formulations are the only tool that create a direct barrier to opioid abuse specifically through non-oral routes.

Similarly, the levelling of heroin overdose deaths may reflect its displacement in illicit distribution channels by synthetic opioids, including fentanyl and fentanyl analogs clandestinely manufactured at labs in far-flung places including China, Mexico, Bulgaria, Greece, Slovakia, Belarus, the Ukraine and Russia, and trafficked through both traditional illicit drug distribution channels, and increasingly, over the internet. Starting in 2016, the number of overdose deaths involving synthetic opioids surpassed heroin and prescription opioids. In some cases, manufacturers of illicit opioids and/or drug dealers are responding to periodic declines in the purity of heroin by using synthetic opioids as heroin adulterants to maintain stable retail pricing. In other cases, synthetic opioids entirely substitute for heroin. Fentanyl precursors are also being shipped from China to individuals and drug cartels for processing and distribution across the U.S. They are used to manufacture of fentanyl-laced pills sold as counterfeit oxycodone or hydrocodone, thus underscoring the need for a robust harm reduction strategy. Some of the synthetic opioids are characterized by new features, including ease of availability on the web, low price and high purity. Many of the new synthetic opioids are derived or resurrected from patent filings or published scientific literature of pharmaceutical companies.

The increase in opioid overdose and deaths is not for lack of significant efforts on the part of various operating divisions of the HHS, including the NIDA, SAMHSA and FDA. These efforts have included (i) the NIH HEAL Initiative, a public-private partnership in conjunction with the FDA to address the opioid crisis via more safe and effective ways to prevent and treat OUD and overdose; (ii) increased access to and dispending of the opioid overdose reversal agent, naloxone; (iii) expanded access to medication-assisted treatments, particularly the recently introduced monthly buprenorphine injectable, Sublocade™; (iv) NIDA’s growing emphasis on funding high impact OUD and opioid overdose research directed at FDA approval of putative therapeutics; and (v) more effective linking of individuals with OUD to treatment and harm-reduction services. Without significant Congressional appropriations for the opioid overdose crisis, and intervention by various stakeholders, the devastation from the opioid overdose crisis would be far greater.

Unfortunately, things could get worse before they get better. Synthetic opioids are an increasingly major public health hazard which present unique interdiction challenges. The worldwide recreational drug market is being flooded at a rapid pace with a diversity of synthetic compounds. Fentanyl has a potency adjusted molecular mass 30 to 50-fold lower than heroin, making it much easier to conceal in first class mail and at ports of entry. Recent interdiction data show that while illicitly manufactured fentanyl is the predominant synthetic opioid, increasingly, many fentanyl analogs and structurally-diverse non-fentanyl synthetic opioids are being encountered as adulterants in illicit heroin or as constituents of counterfeit prescription opioids.