Giving Naloxone, Trainings in Overdose Reversal, and Harm Reduction Doesn’t Seem to Reduce Deaths by Opioid Overdoses

The HEALing Communities Study (HCS), the largest addiction prevention and treatment study ever conducted, launched in 2019 across 67 communities in Kentucky, Massachusetts, New York, and Ohio—states deeply impacted by the opioid crisis. The National Institutes of Health (NIH) awarded $344 million to fund the HEALing Communities study. The focus was on overdose education, naloxone distribution, and medications treating opioid use disorder (OUD). This historic effort, launched in April 2018, was touted to reduce opioid deaths by 40 percent, boost addiction medicine, and create an infrastructure to coordinate responses to OUD.

The Healing Communities study reported recently in the New England Journal of Medicine (https://www.nejm.org/doi/full/10.1056/NEJMoa2401177) identified 19 evidence-based recovery strategies to implement in the U.S. Evidence-based practices for reducing opioid-related overdose deaths include overdose education and naloxone distribution, the use of medications for the treatment of opioid use disorder, and prescription opioid safety

Communities were randomly assigned to either receive the intervention (between January 2020 and June 2022) or to the control group (which received the intervention between July 2022 and December 2023). To test the effectiveness of the intervention on reducing opioid-related overdose deaths, researchers compared the rate of overdose deaths between the communities that received the intervention immediately with those that did not during the period of July 2021 and June 2022.

Factors like exclusively focusing on overdose reversal, rather than intervention and treatment, the COVID-19 pandemic and the surge of fentanyl in the drug market likely affected the study’s outcomes. If, for example, we just supported the treatment of alcohol poisoning or detoxification from alcohol, we should expect similarly poor outcomes. Addiction researchers have always emphasized that while harm reduction is crucial, it’s not a cure for addiction. Many patients overdose multiple times, drop out of treatment and overdose again. OUD is a chronic, relapsing condition. Successfully treating their overdoses was important, but they might ultimately still die of an opioid overdose or consequence of their OUD. Often overdose and OUD emerges as a result of self-medication from pain, depression, anxiety, trauma, PTSD, and suicidal thinking. The study highlights the need for long-term strategies, including methadone treatment and better-funded prevention initiatives. Although the results were discouraging, the study successfully implemented evidence-based practices and engaged communities, offering insights for future interventions.

Despite implementing solid, evidence-based public health and overdose reversal strategies, the NEJM original article clearly showed that the study did not help outcomes or prevent overdose deaths. The HEAL communities did not see a statistically significant reduction in opioid overdose deaths due to several factors:

The Opioid Crisis as a Moving Target: The rapidly evolving nature of the opioid crisis, particularly with the rise of counterfeit fentanyl-containing pills and the mixing of fentanyl with other drugs like heroin, cocaine, and methamphetamine, made traditional public health approaches less effective. Strategies designed for heroin overdoses, such as using low doses of naloxone, became outdated as fentanyl became more prevalent and posed new challenges for harm reduction.

Harm Reduction vs. Prevention: While harm reduction is vital, it is not a cure for addiction, a chronic and relapsing condition often leading to premature death. Over 20 percent of opioid overdose victims had received naloxone but died regardless, highlighting the limitations of harm reduction. The need for long-term solutions, such as methadone treatment and broader prevention initiatives, is critical.

Lessons from Tobacco Control: The success of anti-tobacco campaigns in the mid-20th century shows the importance of stigmatizing dangerous substances and changing social norms. Unlike addiction treatment, the reduction in smoking rates was driven by public campaigns, legislation, and taxation rather than new treatments. A similar approach could be effective in combating the opioid crisis by focusing on prevention and raising awareness about the dangers of drug use.

The Need for New Prevention Strategies: The current focus on medication-assisted treatments (MATs) and harm reduction has overshadowed the need for innovative prevention strategies. There has been little investment in preventing drug use, despite its cost-effectiveness in reducing new cases of addiction. Anne Milgram’s “One Pill Can Kill” could be an effective preventive message. Programs like the Office of National Drug Control Policy’s Drug-Free Communities, which have proven success reducing youth substance use, should be part of community evidence-based solutions.

There has been almost no new investment in stopping or delaying drug use in the first place—the most cost-effective way to reduce the number of new people entering pathways leading to overdose and death. Successful programs like the Drug-Free Communities initiative should be expanded to include prevention efforts targeting youth. Prevention is an underfunded and complementary addiction strategy.

Overdose is a serious and life-threatening event which Brian Fuerhlein, MD, PhD and his colleagues at Yale have reversed and initiated treatment in the Emergency Room. Yale University Department of Psychiatry a free-standing psychiatric emergency room at the VA (Veterans Administration) in Connecticut. They observe patients longer than the typical six hours in a medical emergency room, monitor patients for symptoms of opioid withdrawal, typically using the clinical opiate withdrawal scale (COWS), observe patients for 48 hours or more to stabilize them on buprenorphine prior to discharge. Using COWS as a guide buprenorphine protocol (4mg followed by 4mg soon thereafter, with 8mg on day one and 16mg on day two) is generally initiated and long-term engagement encouraged with an outpatient team for continued maintenance. Until cures are found, long-term buprenorphine or methadone treatment with 5-year outcomes need support and reporting.

Supporting Long-Term Recovery: Decades of experience in treating physicians and other healthcare providers with OUDs and SUDs have shown that long-term treatment can lead to high recovery rates. However, such comprehensive treatment is not widely available to the general population. Expanding access to long-term care and addressing the treatment-resistant aspects of OUD could improve outcomes for more individuals.

Discouragingly, an ambitious study recently reported in the New England Journal of Medicine did not prove evidence-based interventions like distributing naloxone (Narcan) and providing access to medication-assisted treatments (MATs) significantly curbed opioid deaths. Likely reasons for these findings start with the opioid epidemic as a moving target. False dichotomy either/or thinking is another issue, as both prevention and harm reduction are crucial to saving lives. Trying to end or delay use is also an unacknowledged but viable strategy. Bottom line is primary prevention of drug use is underutilized and very poorly funded. It is clear substance use disorders starting in 10-year-olds or teens need very different interventions and treatments than SUDs in physician addicts in their 30s.

The HEALing Communities Study, while not reducing deaths as expected, made significant strides in community engagement, best practices, and treatment system development. “This study brought researchers, providers, and communities together to break down barriers and promote the use of evidence-based strategies that we know are effective, including medications for opioid use disorder and naloxone,” said NIDA director, Nora D. Volkow, M.D. “Yet, particularly in the era of fentanyl and its increased mixture with psychostimulant drugs, it’s clear we need to continue developing new tools and approaches for addressing the overdose crisis. Ongoing analyses of the rich data from this study will be critical to guiding our efforts in the future.”

Addiction is a chronic, relapsing, long-term disease, often ending with premature death. Harm reduction is important but not a cure, as more than 20 percent of all opioid overdose decedents received naloxone but died anyway. NIDA has funded new treatment development and research on overdose, psychedelics, brain neuromodulation, neurosurgery, immunological treatment, and vaccines. Focusing on at least five years of methadone treatment makes harm reduction and treatment sense.

Harm reduction doesn’t equal prevention or cure. Naloxone distribution and encouraging medication-assisted treatments are lifesaving. They are often the last resort compared to prevention or interventions. Future success may come from combining harm reduction with prevention strategies, particularly among youth and young adults, to address the ongoing and evolving opioid crisis in the U.S. While the headline now is failure of harm reduction, the data will continue to be evaluated. Said National Institute on Drug Abuse (NIDA) director Nora Volkow, M.D., “This study brought researchers, providers, and communities together to break down barriers and promote the use of evidence-based strategies that we know are effective.” She added, “It’s clear we need to continue developing new tools and approaches for addressing the overdose crisis…”