Why Gabapentinoid Prescribing Is Rising Despite Declines in Opioid Use

Chronic Pain Treatment and Evolving Prescribing Patterns

Emerging data published in JAMA showcase the shift in how doctors help their patients through chronic pain.¹ Although there is a decline in long-term opioid therapy (LTOT), there has been a significant increase in the coprescribing of gabapentinoids alongside opioids.¹ Efforts to subdue overall opioid use have improved, but the combination of opioids with central nervous system depressants (gabapentin, pregabalin, and benzodiazepines) is growing more common and raises safety concerns, including excessive sedation, dizziness, respiratory depression, and the risk of overdose. 

For patients who have not responded effectively to nonopioid pain management therapies and medications, LTOT remains a viable option. However, opioid usage has a common association with addiction, misuse, and overdose.² Due to these complications, the CDC highlights prioritizing nonopioid therapies such as nonsteroidal anti-inflammatory drugs and physical therapy for patients before considering opioid therapy. Likewise, the CDC recommends a deep evaluation as to whether opioid therapy is truly essential and safe for the patient.²

With fewer opioids being prescribed, other drugs such as gabapentin and pregabalin have become more widely used to treat pain. These agents are commonly prescribed off-label for neuropathic and chronic pain conditions.³ Although this is interpreted as a safer alternative, emerging data suggest the concurrent use of these agents with opioids creates a higher risk of sedation and respiratory depression.³

In 2019, the FDA released an official warning on life-threatening breathing complications in association with gabapentinoids when used in combination with opioids or other central nervous system (CNS) depressants.⁴ Older patients and patients with multiple comorbidities are especially susceptible to these complications.

Study Overview

Nguyen et al conducted a retrospective analysis using the IQVIA Longitudinal Prescription Database, which captures approximately 92% of US retail pharmacy prescriptions.¹ The study evaluated trends in LTOT and coprescribing patterns between 2015 and 2023. LTOT was defined as opioid use lasting at least 90 days, with additional criteria including 120 days’ supply or more, or 10 or more prescription fills within a 180-day period.¹ The investigators also assessed concurrent prescribing of gabapentinoids, benzodiazepines, and stimulants, along with demographic and payer trends.¹

Key Findings

The number of patients receiving LTOT declined from 5.6 million in 2015 to 4.2 million in 2023, representing a 24.3% reduction.¹ Despite this decrease, LTOT remains prevalent, affecting millions of individuals nationwide.¹ Coprescribing trends shifted notably during the study period. Gabapentinoid coprescribing increased from 47.0% to 58.7%, whereas benzodiazepine coprescribing decreased from 43.8% to 33.5%.¹ Stimulant coprescribing increased slightly from 5.9% to 6.7%.¹ The study population also aged significantly, with mean age increasing from 52.5 to 60.5 years.¹

By 2023, Medicare became the primary payer for LTOT, reflecting a growing burden of chronic pain management among older adults.¹ Additionally, average opioid dosing declined from 47.9 to 38.6 morphine mg equivalents, suggesting more conservative prescribing practices.¹ However, increased reliance on combination therapy may offset some of the intended safety benefits.¹ A secondary report summarizing these findings similarly emphasized that millions of Americans remain on LTOT and that coprescribing with gabapentinoids continues to rise.⁵

Clinical Implications for Pharmacists

Treatment for chronic pain is constantly shifting. Although the reduced prescribing of opioids is optimistic news, the increased prescribing of gabapentinoids that follows introduces new risks related to additive CNS depression. Pharmacists play an essential role in assisting patients with reducing risks through comprehensive medication review, educating patients on how to safely take their medication, monitoring for adverse effects (AEs), and collaborating with the patient’s health care providers to assist with adjusting or improving therapy. Pharmacists have the ability to analyze a patient’s current medication to identify any high-risk drug combinations, such as opioids and gabapentin. It is essential to monitor any visible AEs, such as extreme drowsiness or slowed/delayed breathing. Pharmacists are also able to ensure certain doses of medication aren’t too high or too low, or that a medication is no longer needed.

Although long-term opioid therapy has declined in the US, it remains a common treatment for chronic pain.¹ The concurrent rise in gabapentinoid coprescribing represents an emerging safety concern due to the risk of additive CNS depression and respiratory compromise.

REFERENCES

1. Nguyen TD, Chua KP, Jiao A, Bicket MC, Bohnert A, Lagisetty P. US trends in long-term opioid therapy. JAMA. Published online April 8, 2026. doi:10.1001/jama.2026.3241

2. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC clinical practice guideline for prescribing opioids for pain—United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1

3. Goodman CW, Brett AS. Gabapentin and pregabalin for pain—is increased prescribing a cause for concern? N Engl J Med. 2017;377(5):411-414. doi:10.1056/NEJMp1704633

4. Neurontin, Gralise, Horizant (gabapentin) and Lyrica, Lyrica CR (pregabalin): drug safety communication - serious breathing problems. FDA. December 19, 2019. Accessed April 10, 2026. https://www.fda.gov/safety/medical-product-safety-information/neurontin-gralise-horizant-gabapentin-and-lyrica-lyrica-cr-pregabalin-drug-safety-communication

5. George J. Gabapentin, pregabalin increasingly prescribed with opioids. MedPage Today. April 8, 2026. Accessed April 10, 2026. https://www.medpagetoday.com/neurology/opioids/120704