By Judy George

Gabapentin prescriptions for chronic back pain were linked to higher dementia and cognitive impairment risk.

Risks were especially high for chronic back pain patients ages 35 to 64.

The study highlights potential concerns in light of increasing off-label use of gabapentin.

Gabapentin (Neurontin) prescriptions for chronic low back pain were linked with an increased risk of dementia and cognitive impairment, especially in younger people, an analysis of U.S. healthcare claims suggested.

Among more than 52,000 adults with chronic back pain who were followed for 10 years, those who had six or more gabapentin prescriptions had a higher incidence of dementia (risk ratio [RR] 1.29, 95% CI 1.18-1.40) and mild cognitive impairment (RR 1.85, 95% CI 1.63-2.10) than those not prescribed gabapentin, according to Chong Kim, MD, of MetroHealth Medical Center in Cleveland, Ohio, and co-authors.

Prescription frequency correlated with risk, Kim and colleagues reported in Regional Anesthesia & Pain Medicine. People with 12 or more gabapentin prescriptions had a higher incidence of dementia (RR 1.40, 95% CI 1.25-1.57) and mild cognitive impairment (RR 1.65, 95% CI 1.42-1.91) than those prescribed gabapentin three to 11 times.

Among younger chronic back pain patients -- ages 18 to 64 -- those prescribed gabapentin had over twice the risk of dementia (RR 2.10, 95% CI 1.75-2.51) and mild cognitive impairment (RR 2.50, 95% CI 2.04-3.05) compared with their counterparts who didn't have gabapentin.

There was no heightened risk among people 18 to 34 years old who were prescribed the drug, but dementia risk was more than double and mild cognitive impairment risk more than triple among those ages 35 to 49. A similar pattern emerged among those 50 to 64 years old.

In people ages 65 and older, the gabapentin group had an increased incidence of both dementia (RR 1.28, 95% CI 1.15-1.42) and mild cognitive impairment (RR 1.53, 95% CI 1.28-1.83).

"This project highlights a potential concern for prescribing practitioners to consider, particularly with the increasing use of gabapentin for off-label conditions, as well as the need for continuing evaluation of efficacy and risks of any treatment," said Kim.

"Due to the design of the project, the results have limitations, and further studies are needed to validate the findings," he added.

Gabapentin is approved for seizures and post-herpetic neuralgia; gabapentin enacarbil is approved for restless legs syndrome. Despite limited indications, gabapentin and its cousin, pregabalin (Lyrica), are widely prescribed off-label for various other pain syndromes.

Common side effects of gabapentinoids include drowsiness, dizziness, blurry or double vision, and difficulty with coordination and concentration. In 2019, the FDA warned about serious breathing problems that may occur in patients using gabapentin or pregabalin who have respiratory risk factors. These factors included taking opioids or other drugs that depress the central nervous system, conditions like chronic obstructive pulmonary disease (COPD) that reduce lung function, and older age.

"While existing literature identifies several risks, there lacks a strong understanding of how gabapentin impacts cognitive function and whether it contributes to neurodegenerative processes," Kim and co-authors wrote.

"At the moment, there's not enough evidence to suggest pain medications are linked to higher dementia risk, but this research gives us interesting insights," observed Leah Mursaleen, PhD, of Alzheimer's Research U.K. in Cambridge, who wasn't involved with the study.

"Because this study only used health records of people with chronic pain, we cannot rule out other factors that might be influencing the findings," Mursaleen posted on the U.K. Science Media Center website. "And previous studies looking at people prescribed gabapentin for other conditions, like seizures, didn't show a link between the medication and higher dementia risk."

For this analysis, the researchers used the TriNetX national database of patient records from 2004 to 2024, including adults with chronic low back pain and following them for 10 years. People with prior gabapentin use, dementia, epilepsy, stroke, or cancer were excluded from the study.

Kim and colleagues used propensity score matching to control for demographics, medical diagnoses related to cognitive decline, and pain medications. After propensity score matching, 26,416 chronic back pain patients were in the gabapentin group, and 26,416 were in the no-gabapentin group.

Mean age in both groups was about 53 years. Approximately 58% were female, and 73% were white. In both groups, about 65% received opioid prescriptions, 39% received prescriptions for benzodiazepines, and 29% had skeletal muscle relaxants. Comorbidities -- including hypertension, diabetes, nicotine dependence, alcohol-related disorders, sleep disorders, and others -- were similar in each group.

The study was observational and could not generate causal conclusions, the researchers noted. Electronic medical record data may have been miscoded, and other variables may have influenced results. Neither dose nor duration of gabapentin use was controlled for.

"Our results support the need for close monitoring in adult patients prescribed gabapentin to assess for potential cognitive decline," Kim and colleagues wrote.

"We hope the current study promotes further research to delineate whether gabapentin plays a causal role in the development of dementia and the underlying mechanisms of this relationship."