A major new study claims to add weight to evidence linking gabapentin to cognitive decline.
Within 10 years of their initial pain diagnosis, patients prescribed gabapentin for low back pain were significantly more likely to develop dementia or mild cognitive impairment (MCI).
A US study of more than 50,000 adults found an almost 30% increased risk of dementia and an 85% increased risk of developing MCI among those who received six or more gabapentin prescriptions.
The risk of cognitive decline rose with the number of gabapentin prescriptions a patient received. Patients who had 12 or more prescriptions were 40% more likely to develop dementia and 65% more likely to develop MCI than those prescribed the medication between three and 11 times, the study found.
Using de-identified records of patients with chronic low back pain from between 2004 and 2024 across 68 healthcare organisations, researchers matched 25,000 patients prescribed gabapentin with 25,000 who were not.
Patients with prior gabapentin use, dementia, epilepsy, cancer or a history of stroke were excluded. Propensity score matching controlled for demographics and comorbidities such as mental illness.
Gabapentin use in 18-64-year-olds, a group often considered too young to develop these conditions, was found to more than double the risk of either condition. According to the Australian Bureau of Statistics, dementia occurs in 0.1% of people under the age of 65.
However, study results indicate that 1.1% of 18-64-year-olds in the no gabapentin group developed dementia, compared with 2% of the gabapentin group. The absolute risk of MCI also increased by less than 1% with gabapentin use in this age group.
MCI risk more than tripled in the 35-49 age range with gabapentin use, from 0.4% to 1.4%, and the absolute risk of dementia increased by 0.6% (0.2% vs 0.8%).
For those aged 65 or older, absolute risk of dementia increased by 1.1% (5.3% vs 6.4%) with gabapentin use, but risk of MCI increased by only 0.3% (5.3% vs 5.6%).
Researchers told media that their findings support the need for close monitoring of adult patients prescribed gabapentin to assess for potential cognitive decline.
However, Dr Dilip Kapur, a South Australian anaesthetist and dean of the Faculty of Pain Medicine, told Rheumatology Republic that the study raises concerns about prescribing these drugs in the first place.
“If we’re seeing something genuine here, then the cost to benefit ratio of something like the use of gabapentinoids in back pain may actually be disastrous,” he said.
Dr Kapur explained that the current body of evidence was uncertain, with some large studies finding an association between gabapentin and dementia, while others have concluded no link.
He urged caution for prescribers, explaining that a relative risk increase of 30% for a serious diagnosis like dementia was not trivial.
“Most people wouldn’t accept that risk for anything that they can easily control,” he said.
However, Dr Kapur said that the magnitude of difference in absolute risk being greater in younger people than in older raises suspicions there may be confounders at work in the study.
“I think it requires ongoing vigilance with respect to the use of this class of agents, but we’re not in a good position to come to any firm conclusions at the moment,” he said.
The study could not confirm a causal association between gabapentin use and neurodegeneration, and Dr Kapur raised concerns about the lack of dosage exposure information, the specificity in terms of forms of dementia and certain limitations in the controlling of confounders.
He felt that one important thing they neglected to account for was physical activity, a major protective factor against dementia.
“It may well have been the case of individuals with more severe low back pain who were less active were more likely to be prescribed these drugs,” he said.
He also noted that mental health was not well detailed, with no clear distinction between anxiety and depression, and described the use of ICD codes to classify mental illness as a blunt tool.
Despite this, he believes there do exist plausible biological mechanisms by which gabapentinoids could increase risk of dementia and MCI.
Dr Kapur said that the clear indication for use in neuropathic pain based on efficacy data did not exist for somatic pain, and there was some indication that gabapentinoids were overused in somatic pain.
“For uncomplicated low back pain, there really is no good evidence that these drugs are effective,” he said.
“Doctors are in a very difficult position, because the evidence-based treatments for low back pain are simply not supported by health funding pathways.”
He emphasised that multidisciplinary support and functional restoration were far more effective than pharmacological treatments, which were associated with a risk of serious adverse events.
“A paradigm shift is needed,” he said.
A spokesperson for Viatris, a manufacturer of gabapentin, told RR that she could not comment on the individual study but maintained that Viatris adhered to the pharmacovigilance responsibilities of a medicine sponsor.
“This includes, and is not limited to, the assessment and communication of safety issues and signals that may have a potential impact to the benefit-risk balance of the medicine and/or public health to the regulator, TGA,” she said.
Gabapentin manufacturer Arrotex did not want to comment on the paper.