The FDA recently announced new requirements for opioid medications to be labeled to emphasize “the safety risks of long-term use.” The labeling updates are based on two required postmarketing observational studies on all new opioid analgesics for chronic noncancer pain.
While the labeling changes are intended for patients, FDA also cautioned prescribers and stated that patients should undergo periodic checks for signs of addiction, abuse, or misuse of opioid prescriptions. FDA also requires an additional prospective, randomized, controlled clinical trial to directly examine the benefits and risks of long-term opioid use.
In the press release for this new requirement, FDA Commissioner Marty Makary, MD, MPH, invoked references to “failures of public health” in regard to opioid prescribing, which has been a primary focus for policymakers in addressing overdoses. Yet, this pointed blame misses the actual drivers of the overdose crisis. Based on empirical data and past experience, we can expect the labeling changes to have little to no effect on meaningfully reducing overdose rates. The administration would be wise to concentrate its efforts elsewhere.
What Does the New Guidance Add?
While both studies (based on data from 2006-2016 and 2017-2021, respectively) were limited by their observational nature, they provided a robust data set highlighting the ongoing issue of opioid addiction, misuse, and overdose. The findings were consistent with prior estimates of risks with long-term prescription opioid use. Similarly, these new regulations do not differ significantly from previous CDC guidelines for opioid prescribing dating back to 2016, many parts of which are also regulatory requirements.
It is worth noting that the CDC not only issued updated guidance on these, very similar, prescribing guidelines but actually completely revised them due to both errors in the starting premise as well as adverse outcomes from excessive restrictions on therapeutic use. CDC discovered that prescription opioids were not driving the opioid overdose deaths, well after this had become accepted as mainstream information. Furthermore, the CDC guidelines and other excessive warnings about relatively small — albeit real — risks led to worse outcomes for patients, including inequitable pain treatment, medication shortages, medication errors and untreated pain, and increased rates of suicide in patients with chronic pain, without affecting overdose rates.
Prescription Drugs Are Not Driving the Overdose Crisis
Although prescription opioids like oxycodone (OxyContin) did contribute significantly to increasing rates of opioid use disorder and overdoses early on — and there were examples of pharmaceutical corruption, regulatory failure, and inappropriate prescribing — the public perception of this narrative misses critical points.
The problematic prescription opioids early in our overdose crisis were mainly being prescribed and used inappropriately in the case of “pill mills,” where people would pay for large amounts of prescription drugs like oxycodone with the explicit intent of selling them for nonmedical use. While there were certainly instances of overprescribing, the overwhelming majority of patients taking their own prescription for some medical indication did not end up misusing or becoming addicted to opioids.
This is consistent with FDA’s recent postmarketing studies on those taking opioid analgesics for chronic noncancer pain, showing a less than 10% rate of “abuse” or recreational use, and a 1%-to-6% rate of addiction. This is not to say the risks are insignificant, but these concerns are addressed in CDC and state prescribing guidelines as well as guidance from multiple medical professional organizations.
Furthermore, opioid prescribing rates have been falling since a peak in 2012. As of 2023, the opioid prescription rate was about half that in 2006. Despite consistent and significant decreases in opioid prescribing from 2012 to 2023, opioid overdose deaths increased from 16,007 in 2012 to 79,358 in 2023 — a 496% increase in deaths compared to a 48% decrease in prescriptions. Overdose deaths only finally began to decline in late 2023.
The reason for this complete uncoupling of prescriptions and overdoses in the past decade is because almost all opioid deaths in recent years (and today) have been driven by illicit fentanyl. While fentanyl is also available as a pharmaceutical drug, the regulated version does not cause significant amounts of overdoses or deaths. Moreover, FDA’s new requirements do nothing to address other non-opioid drugs in the illicit supply that cause overdoses.
So, while there is nothing incorrect or inappropriate about FDA’s labeling changes, any claims that this will meaningfully address our ongoing overdose crisis is denial of over a decade of facts.
Actions Speak Louder Than Labels
While the administration takes empty action on labeling requirements, it’s failing to support initiatives far more likely to make a real difference in the overdose crisis.
Overdose deaths continued to increase year after year despite reduced opioid prescribing and stricter prescribing regulations, but overdoses and deaths did finally start to decline after decades during the Biden administration. This has been attributed mostly to broad local initiatives, particularly “harm reduction,” which has not enjoyed the same support from regulators and policymakers.
“Harm reduction” is practiced in almost every condition or disease in modern adult medicine. But when it is applied to substance use, it becomes controversial. Despite the fact that harm reduction saves lives, one of President Trump’s executive orders specifically names “harm reduction” for substance use as something the administration opposes. The impact of this has already been felt at the state and local levels.
Naloxone (Narcan), the lifesaving antidote to all opioid overdoses, is a key component of opioid harm reduction. (Every opioid overdose can be treated with naloxone if given in time.) Despite the fact that this literal lifesaving antidote remains underutilized, this administration has only acted to potentially limit access further.
Recent Medicaid cuts, which will result in an estimated 11 million Americans losing coverage, also threaten to worsen access to overdose and substance use disorder treatment. Medicaid funds an estimated 60% of substance use disorder treatment in the U.S., and even pays for close to 40% of overdose treatment. With all aspects of overdose treatment and prevention critically underfunded, that loss will have significant impacts.
Data show that Medicaid has made a difference in addressing our overdose crisis, and data have also shown that expanding Medicaid would foster even greater results in combatting overdose deaths. The cuts may already be causing negative effects, and they will likely be amplified in red states where substance use issues remain the worst.
Lastly, the administration has placed a significant focus on restricting immigration, as well as international trade, allegedly under the auspices of trying to reduce fentanyl trafficking. Federal law enforcement data show that almost all fentanyl entering this country from abroad comes from American citizens, who bring it through legal checkpoints.
Illicit fentanyl, however, is also made domestically; given the history of supply and demand, any impact on foreign supply — which would likely be miniscule — will only lead to increased domestic production rather than reducing illicit fentanyl. We also continue to gain more evidence that supply-side-only interventions like interdiction and drug seizures actually lead to increases in overdose and a less safe drug supply.
The FDA commissioner and the Health and Human Services secretary have failed to acknowledge any of these points.
Changing the Focus
Prescription opioids come with risks, just like most medications, and these should be carefully weighed by both the prescriber and the patient against their potential therapeutic benefits. Simply reducing opioid prescriptions not only fails to reduce overdoses, it actually leads to increased illicit opioid use.
So, if you care about drug overdoses, don’t be fooled by performative press releases. Actions speak louder than words, and this labeling change will accomplish little if anything.
