Treatment with gabapentin following traumatic brain injury (TBI) may protect the brain, potentially influencing cognition and recovery trajectories, new research hints.

In a large retrospective study, researchers found that the drug was associated with reduced cognitive impairment after mild TBI and reduced mortality after severe TBI. 

“Gabapentin is already commonly used for pain and agitation in TBI, we just didn’t know if it helped cognition,” study investigator Isaac Thorman, ScM, a third-year medical student at New York Medical College in Valhalla, told Medscape Medical News. 

However, he cautioned against overinterpreting the findings in clinical practice at this early stage. 

“Would we say that gabapentin should be prescribed for cognitive impairment? Absolutely not, but the results do call for further investigation in a randomized study,” Thorman said. 

The findings were reported April 19 at the American Academy of Neurology (AAN) 2026 meeting.

Few Pharmacologic Options 

TBI remains a major cause of long-term disability and death worldwide, with survivors often facing persistent cognitive decline, psychiatric complications, and reduced functional independence. 

Despite the burden, there are limited pharmacologic options that meaningfully alter long-term neurological outcomes. Gabapentin, widely prescribed for neuropathic pain and seizure-related indications, has been hypothesized to affect neurorecovery, but robust population-level evidence examining its impact on cognition and mortality after TBI has been limited.

To investigate further, Thorman and colleagues conducted a retrospective longitudinal cohort study using the TriNetX Research Network, analyzing 49,925 adults (mean age, 47 years; 32% women) with documented TBI, including 34,376 with mild TBI (Glasgow Coma Scale [GCS] score 13-15) and 12,845 with severe TBI (GCS 3-8). 

None of the participants had prior gabapentin exposure or preexisting durable cognitive impairment. A total of 1757 patients received gabapentin after TBI. 

About 7% of mild and severe TBI patients developed durable cognitive impairment within 2 years of the brain injury. 

In fully adjusted Cox models, gabapentin use was associated with a significant 22% lower risk of developing durable cognitive impairment among those with mild TBI (hazard ratio [HR], 0.78; P = .03).

Among patients with severe TBI, gabapentin was linked to a 46% lower risk of death at 2 years (HR, 0.54), although no reduction in cognitive impairment was observed in this group, likely reflecting survivorship bias. 

In contrast, treatment with the antiseizure medication levetiracetam showed no protective association.

Use of gabapentin was also associated with higher rates of adverse outcomes, including psychiatric, sleep, and cardiovascular disorders. 

This drug is “widely used and well tolerated, particularly in a population already dealing with severe neurological injury,” said Thorman. The adverse events observed in the study were “pretty much par for the course” given gabapentin’s long history of use, he added. 

However, he emphasized that the findings are observational and do not establish causality, noting the potential for residual confounding in a nonrandomized design. 

“We show an association being gabapentin use and improved cognition and reduced mortality, but we can’t say the gabapentin caused these benefits,” Thorman cautioned. 

He added that the results should be viewed as hypothesis-generating but noted that the magnitude of the observed associations supports further investigation. 

Easing the Secondary Storm

Reached for comment, Shaheen Lakhan, MD, PhD, neurologist and researcher based in Miami, Florida, said the “signal” revealed in this study has “biologic plausibility.”

“My read is that gabapentin may not be neuro-protective in the traditional sense, it may be recovery-protective.”

“After TBI, the first hit is only part of the story,” Lakhan explained. “What often determines outcome is the secondary storm that follows: hyperexcitability, poor sleep, pain, agitation, autonomic overdrive, and inflammatory stress. If you calm that storm, you may improve the trajectory even if you don’t reverse the initial injury.”

“Gabapentin is interesting because it may do exactly that. By modulating calcium-channel signaling and reducing excessive neuronal firing, it could help stabilize vulnerable circuits,” said Lakhan, who was not part of the study. 

“Just as importantly, it can improve sleep, reduce pain amplification, and quiet an overactivated nervous system. Those effects may sound supportive rather than dramatic, but in brain injury, supportive physiology can be decisive,” Lakhan said. 

“Put simply, sometimes the best way to protect the brain is not to chase the injury, it’s to optimize the environment in which the brain heals,” he added. 

Lakhan suggested that while gabapentin is unlikely to protect neurons during the acute emergency phase, it may still play an important role in improving recovery in the weeks after a traumatic brain injury. 

He emphasized that this is a clinically meaningful and testable idea — one that doesn’t yet warrant changes in practice but clearly deserves further study. If a safe, widely available, and low-cost drug can meaningfully enhance post-TBI recovery, he noted, its impact could be as significant as that of a traditional neuroprotective breakthrough.

The study had no specific funding. Disclosure information for study authors is available in the original study publication. Lakhan had no disclosures.