New FDA Guidance Seeks to Expand Nonopioid Options to Manage Chronic Pain and Curb Misuse

1 in 5 People With Chronic Pain Continue to Receive Opioid Analgesics

The FDA has released comprehensive draft guidance aimed at accelerating the development of safe, effective nonopioid treatments for chronic pain while reducing prescription-related opioid misuse. The "Development of Non-Opioid Analgesics for Chronic Pain" guidance provides pharmaceutical developers with clearer regulatory pathways to bring alternative pain management therapies to market faster, according to an agency statement.

Addressing an Ongoing Crisis

FDA Commissioner Marty Makary, MD, MPH, emphasized the continued urgency of the opioid crisis, stating that "physicians need more alternatives to opioid medications for people suffering from chronic pain." Despite recent declines in opioid prescribing, approximately 1 in 5 US adults living with chronic pain still receive opioid prescriptions due to limited effective alternatives, the agency stated. While the development of opioid misuse is not universal among those treated long-term with the analgesics, the CDC estimates the rate of opioid misuse to be between 8% and 12%.2

"America's opioid crisis is not over. We must stay vigilant to address this longstanding problem in new ways," Makary noted. "FDA can help by providing clear guidance like this, which makes regulatory pathways more predictable for innovators and drug developers, enabling effective, lower-risk therapies to quickly reach the millions of Americans living with chronic pain."

Key Regulatory Considerations

The draft guidance addresses 4 critical areas that drug developers must navigate when developing nonopioid analgesics:

Indication Strategies: The guidance clarifies how developers can establish indications across different scopes, from broader categories covering multiple chronic pain conditions to individual condition-specific indications. The flexibility may allow pharmaceutical companies to better tailor development strategies based on a new compound's mechanism of action and to target patient populations.

Clinical Trial Design: The FDA emphasizes robust evaluation of safety and efficacy through innovative trial designs. The guidance specifically highlights the importance of mechanistic understanding of both the investigational drug and the chronic pain conditions being treated.

Opioid Reduction Outcomes: A key focus involves evaluating nonopioid drugs' ability to avoid, reduce, or eliminate opioid use. The guidance provides developers with frameworks for demonstrating meaningful opioid-sparing effects, which could become a significant differentiator in the chronic pain treatment landscape.

Advanced Development Tools: The guidance calls for incorporating statistical principles, patient-reported outcomes, and expedited programs to support accelerated drug development.

The agency explained that the new guidance fulfills a requirement of Section 3001(b) of the SUPPORT (Substance use-disorder prevention that promotes opioid recovery and treatment for patients and communities) Act, which directs the FDA to provide guidance on the challenges of developing nonopioid pain treatments. The law underscores the urgent need for regulatory clarity in this area.

Broader FDA Strategy

The new guidance represents one component of the FDA's comprehensive strategy to combat the opioid crisis. Other initiatives include requiring safety labeling changes for opioid pain medications like OxyContin to better reflect current evidence, enhancing enforcement around illegal opioid product importation and sales, and supporting nonopioid alternative development.

The FDA encourages public input on the draft guidance through a 60-day comment period following publication in the Federal Register. Stakeholders can submit feedback electronically at www.regulations.gov or in writing to the Dockets Management Staff, referencing FDA-2025-D-0610.

Clinical Implications

The FDA's proposed streamlined development pathways could accelerate the availability of new nonopioid analgesics, potentially providing clinicians with more tools to manage chronic pain effectively while reducing dependence on opioid medications.

The emphasis on patient-reported outcomes and opioid-sparing effects aligns with current clinical priorities, focusing on treatments that not only manage pain but also reduce the risk of opioid-related adverse events and dependency issues that continue to impact patient care and public health.

References

1. FDA issues new guidance to expand non-opioid options for chronic pain, curb misuse. News release. US Food and Drug Administration. September 10, 2025. Accessed September 11, 2025.

2. Dahlhamer JM, Connor EM, Bose J, Lucas JW, Zelaya CE. Prescription opioid use among adults with chronic pain: United States, 2019. National Health Statistics Reports. No 162. August 5, 2021. Accessed September 12, 2025. https://www.cdc.gov/nchs/data/nhsr/nhsr162-508.pdf