A large medical records study suggests that adults who receive multiple prescriptions of gabapentin for chronic low back pain may face a significantly increased risk of developing dementia or mild cognitive impairment. The research, published in Regional Anesthesia & Pain Medicine, found that patients with six or more prescriptions were 29% more likely to be diagnosed with dementia and 85% more likely to develop signs of mild cognitive impairment within a decade. The association appeared especially pronounced in adults under the age of 65.
Gabapentin is a prescription medication originally approved by the U.S. Food and Drug Administration in 1993 to treat partial seizures. Over the years, its use has expanded to include the management of chronic pain, particularly nerve-related conditions such as postherpetic neuralgia and diabetic neuropathy. It is commonly viewed as a safer alternative to opioids due to its relatively low potential for abuse.
Gabapentin acts on the nervous system by binding to a specific subunit of voltage-gated calcium channels in the brain. This mechanism reduces the release of excitatory neurotransmitters and helps diminish the sensation of pain. While the drug is not classified as a controlled substance at the federal level in the United States, its off-label use has grown substantially. Along with this rise in popularity have come growing concerns about its long-term effects on brain function.
“Gabapentin is a drug that was initially approved to treat seizures,” said study author Nafis B. Eghrari, a 4th-year medical student at Case Western Reserve University School of Medicine. “It has shown promise in treating nerve-related pain, and it has become a popular choice to treat chronic low back pain, despite limited evidence.”
“Currently, there is a discrepancy on whether taking gabapentin increases a patient’s risk for developing dementia. Moreover, there lacks a strong understanding of how gabapentin impacts cognitive function and whether it contributes to neurodegenerative processes. Previous studies have shown mixed findings on this topic. Thus, we decided to explore this gap in the field.”
The researchers carried out a retrospective cohort study using deidentified patient data from TriNetX, a national health research network that includes records from 68 healthcare organizations across the United States. They identified adult patients who had been diagnosed with chronic low back pain or related conditions between 2004 and 2014. These patients were tracked for at least ten years following their initial diagnosis to observe any subsequent development of cognitive problems.
To reduce the influence of confounding variables, the researchers excluded patients with a history of conditions known to increase dementia risk, including prior gabapentin use, epilepsy, stroke, and cancer. They also used a method called propensity score matching to ensure that patients who received gabapentin prescriptions were comparable to those who did not in terms of demographics, medical history, and other medications taken for pain.
After matching, the final sample included 26,416 patients who received six or more gabapentin prescriptions and a matched group of 26,416 patients who did not receive the drug. The average age in both groups was just over 52 years, and a slight majority were female. The researchers tracked whether these individuals received a diagnosis of dementia or mild cognitive impairment within ten years of their first back pain diagnosis.
The study also included several subgroup analyses. Patients were divided into younger (ages 18–64) and older (65+) groups, and then further stratified into smaller age ranges. The researchers also compared patients who received 3–11 prescriptions to those who received 12 or more to explore whether the risk increased with more frequent use.
The results suggest that gabapentin use was linked to an increased risk of cognitive decline. Among all adults, those who received six or more prescriptions had a 29% higher risk of being diagnosed with dementia and an 85% higher risk of being diagnosed with mild cognitive impairment compared to those who did not receive the drug.
The risk was not limited to older adults. In fact, the increase in risk was more pronounced in younger patients. Among individuals between the ages of 18 and 64, those who received gabapentin prescriptions had more than twice the risk of being diagnosed with dementia or cognitive impairment compared to their non-medicated peers. Within that group, the risk was especially elevated for people aged 35 to 64.
“We were surprised to find this relatively higher risk in the non-elderly population,” Eghrari told PsyPost. “These results indicate that gabapentin may have a greater cognitive impact on non-elderly individuals, as elderly individuals are already at risk for neurodegeneration due to their older age. This finding warrants further investigation into the underlying mechanism of how gabapentin may impact cognition.”
The researchers also found evidence that more frequent gabapentin prescriptions were associated with greater risk. Patients who received 12 or more prescriptions were significantly more likely to develop dementia or cognitive impairment than those who received between 3 and 11 prescriptions. This pattern held true across both age groups.
While the absolute risk of dementia was relatively low in younger adults, the relative increase in risk among gabapentin users was striking. For example, among patients aged 50 to 64, those with 12 or more prescriptions were nearly twice as likely to be diagnosed with dementia compared to those with fewer prescriptions.
Gabapentin’s potential cognitive side effects have been noted in earlier research, including reports of memory issues, mental fog, and sedation. These effects have been observed in patients with chronic pain, spinal cord injuries, and even in healthy older adults. Some studies suggest that gabapentin may reduce neuroplasticity or interfere with normal signaling in brain regions involved in memory and attention.
At the same time, other studies have suggested the drug may be well tolerated, particularly in patients with epilepsy or agitation related to dementia. The current findings add to an ongoing debate and highlight the need for greater clarity about the drug’s long-term cognitive effects, particularly outside of its original use in seizure treatment.
The researchers suggest that the stronger association seen in younger patients could be due to the fact that older adults already face a higher baseline risk for neurodegenerative disorders, making relative changes harder to detect. It is also possible that age-related differences in how the body metabolizes gabapentin may play a role.
“In terms of clinical significance, I recommend that physicians prescribing gabapentin for chronic pain perform cognitive exams on a regular basis when seeing patients,” Eghrari said. “I’d also advise patients who are taking this drug to alert their physician if they notice any cognitive deficits, including confusion, poor memory, or slowed thinking.”
While the study included a large sample and attempted to control for a wide range of confounding factors, it remains observational. This means it cannot prove that gabapentin caused dementia or cognitive impairment. Other unmeasured variables could have influenced the results, such as dosage, duration of treatment, or severity of underlying pain.
Future studies could build on this work by exploring the biological mechanisms that might link gabapentin use to changes in brain function. Experimental studies in animals or long-term clinical trials in humans may help clarify whether gabapentin contributes directly to neurodegeneration or whether the observed associations reflect other factors.
“The key takeaway of this study is that patients prescribed gabapentin for chronic back pain should be closely monitored by their physician for cognitive decline,” Eghrari said. “Moreover, gabapentin should be prescribed with caution due to the associated risk of dementia/cognitive impairment. We hope to carry this research forward and explore whether there is a true causative relationship between gabapentin and cognitive impairment. We also plan to investigate the underlying mechanisms of how the drug may impact cognition.”
The study, “Risk of dementia following gabapentin prescription in chronic low back pain patients,” was authored by Nafis B Eghrari, Isabella H Yazji, Bryan Yavari, Gustaf M. Van Acker, and Chong H. Kim.
