PHARMACIST STEVE

 New research questioned old assumptions

https://www.medpagetoday.com/neurology/painmanagement/119247

In January 2025, we reported that some adverse events associated with gabapentin (Neurontin) may have been overestimated. Since then, new risks related to gabapentin emerged and prescribing continued to rise. Here’s what we learned about gabapentin in 2025.

Often championed as a safer alternative to opioids and prescribed off-label for chronic pain, gabapentin is approved officially for postherpetic neuralgia and partial-onset seizures. The drug’s label carries serious warnings about dizziness, suicidal thoughts, respiratory depression, and other adverse effects. Another gabapentinoid, pregabalin (Lyrica), is approved for the same indications, plus neuropathic pain and fibromyalgia.

New Risks, Rising Prescriptions

Perhaps the most startling finding about gabapentin in 2025 came from a study that suggested gabapentin prescriptions for chronic low back pain were linked with increased risks of dementia and mild cognitive impairment, especially in younger people.

Among more than 52,000 adults tracked for 10 years in U.S. healthcare claims records, chronic pain patients with six or more gabapentin prescriptions had a higher incidence of dementia and mild cognitive impairment compared with those not prescribed gabapentin. Dementia risk was more than double — and mild cognitive impairment risk was more than triple — among those ages 35 to 49, the researchers reported in Regional Anesthesia & Pain Medicine. A similar pattern emerged among those ages 50 to 64 years.

A dose-response pattern emerged: pain patients who filled 12 or more prescriptions faced greater risks than those with fewer refills. This raised critical questions, especially as gabapentin’s off-label use continued to climb, the study authors noted.

A new report also documented gabapentin’s meteoric rise since 2010. Gabapentin was the fifth most dispensed drug in U.S. retail pharmacies in 2024, CDC researchers said in Annals of Internal Medicine.

Prescriptions per 1,000 people more than doubled from 2010 to 2024, while the number of Americans taking gabapentin soared from 5.8 million to 15.5 million. Statewide policy changes after 2016 — including drug monitoring programs and reclassification of gabapentin as a controlled substance — may have slowed the pace of growth in some places, the CDC team suggested.

In 2025, a claims analysis showed that stroke patients who started gabapentin for pain within 30 days of hospital discharge often received a yearlong gabapentin prescription. The study, posted on medRxiv and not yet peer-reviewed, was the first to provide insights into real-world gabapentin treatment patterns among older Medicare stroke survivors, the researchers said.

More recently, an analysis in JAMA Network Open questioned whether prescribing cascades — a pattern in which the adverse effects of one medication are treated with another — were tied to gabapentinoid-induced edema. A study of medical records of gabapentin-treated military veterans showed that clinicians almost never explicitly considered gabapentinoid effects when treating edema with loop diuretics, commonly attributing fluid build-up to congestive heart failure or venous stasis. Nearly one in four patients had potential harms from a resulting prescribing cascade.

Global research echoed U.S. prescribing concerns. Uncertainty was a recurring theme in a 2025 review of qualitative studies in the European Journal of Pain, with clinicians worldwide saying there was lack of guidance for starting, monitoring, or tapering gabapentinoid use.

Old Warnings Reconsidered

Contrary to previous findings, a commercial claims analysis in 2025 suggested that gabapentin was not associated with greater risk of falls in older adults with neuropathy or fibromyalgia when compared with duloxetine (Cymbalta).

The largest studies that previously estimated gabapentin’s fall risks compared its use against patients who didn’t use medications, the researchers noted in Annals of Internal Medicine. This might mean gabapentin’s risks were overestimated, which could lead to pain being undertreated, they observed. Including an active comparator like duloxetine helped lower the chance that outcomes were driven by confounding by indication.

Long-standing fears about gabapentinoids and self-harm also were re-examined in a U.K. self-controlled case series. That study, published in The BMJ, showed that self-harm risk rose in the 90 days before gabapentinoid treatment, persisted during the early treatment period before dropping to a reference level, then rose again within 14 days after treatment stopped.

“These findings do not support a direct effect of gabapentinoid treatment on self-harm but underscore the necessity for close patient monitoring of self-harm throughout the gabapentinoid treatment journey,” the study authors stated.

Additional research in 2025 illustrated that pregabalin carried a higher risk of heart failure compared with gabapentin among Medicare beneficiaries with chronic noncancer pain. The finding prompted calls from researchers and editorialists in JAMA Network Open for thorough cardiovascular risk assessments before prescribing pregabalin to older patients.

Filed under: General Problems