The anticonvulsant gabapentin has been linked to a significantly increased risk of developing mild cognitive impairment (MCI) or dementia. However, some experts are urging caution in interpreting the study.
After adjusting for demographics, comorbidities, and use of other pain medications, adults prescribed gabapentin for chronic low back pain had a 29% higher risk of developing dementia and an 85% higher risk of MCI within 10 years, compared to those with back pain who were not prescribed the drug.
This finding provides “a foundation to further research whether gabapentin plays a causal role in the development of dementia and cognitive decline,” the investigators, led by Nafis Eghrari, Case Western Reserve University School of Medicine, Cleveland, Ohio, wrote.
In the meantime, they said their observations “support the need for close monitoring of adult patients prescribed gabapentin to assess for potential cognitive decline.”
The study was published online July 10 in Regional Anesthesia & Pain Management.
Hidden Cognitive Cost of Pain Relief?
Gabapentin has become a common go-to alternative to opioids for chronic pain because of its low abuse potential, but its association with cognitive decline and dementia remain unclear.
To investigate, Eghrari and colleagues used the TriNetX national database of de-identified patient records to recreate a propensity-score matched cohort of 26,416 gabapentin users and an equal number of nonusers.
In the initial analysis of all adults aged 18 and older, gabapentin prescription was associated with a higher incidence of dementia (risk ratio [RR], 1.29) and MCI (RR, 1.85).
To explore age-dependent differences, the researchers stratified the cohort into elderly (age ≥ 65) and nonelderly (age 18-64) groups.
In the elderly cohort, gabapentin prescription was associated with increased incidence of both dementia and MCI (RR 1.28 and 1.53, respectively). Similarly, dementia and MCI were more commonly diagnosed in nonelderly gabapentin users than nonusers (RR 2.10 and 2.50, respectively).
The researchers further stratified the nonelderly group into narrower age ranges: 18-34, 35-49 and 50-64 years. Among the 18-34 age group, there was no significant difference in dementia or MCI incidence between gabapentin users and nonusers.
In contrast, patients aged 35-49 who were prescribed gabapentin had an increased likelihood of both dementia (RR, 2.44) and MCI (RR, 3.50). A similar pattern was observed in the 50-64 age group, where gabapentin exposure was associated with elevated incidence of dementia (RR, 2.28) and MCI (RR, 2.22).
The risk increased further with prescription frequency: patients with 12 or more gabapentin prescriptions had a higher incidence of dementia (RR, 1.40) and MCI (RR, 1.65) than those prescribed gabapentin 3-11 times.
Interpret With Caution
Several experts offered perspective on the study in a statement from the UK nonprofit Science Media Centre.
Martin Prince, professor of epidemiological psychiatry, King’s College London, cautioned that “confounding and reverse causality are tenable explanations for the observed effects.”
Tara Spires-Jones, director of the Centre for Discovery Brain Sciences at the University of Edinburgh in Scotland, noted that “while authors used statistical methods to try and account for other risk factors, this type of study cannot prove that gabapentin was the cause of increased dementia risk.”
“One very important factor that was not examined in this study is levels of physical activity. People with chronic pain requiring gabapentin may have been less physically active, which is a known risk factor for developing dementia,” Spires-Jones said.
Prof Sir John Hardy, group leader at the UK Dementia Research Institute at University College London said while the study is “interesting, one has to worry that these types of findings are artefactual and result (for example) from a marginal acute effect on cognitive performance rather than effects on the underlying disease.”
Ian Maidment, professor in clinical pharmacy, Aston University, Birmingham, England, noted that the study did not control for length of treatment or dose of gabapentin and further noted that “other similar recent studies have failed to find a link.”
In Maidment’s view, “the jury is out on whether gabapentin causes dementia.”
The study had no specific funding. Eghrari, Prince, Maidment, and Spires-Jones declared no conflicts of interest. Hardy has consulted for Eisai.