Can gabapentin (anticonvulsant medication) cause cognitive impairment?

Gabapentin and Cognitive Impairment

Yes, gabapentin can cause cognitive impairment, including thinking abnormalities, somnolence, dizziness, and memory problems, as documented in FDA labeling and supported by recent population-based research showing increased dementia risk. 1, 2

Evidence from FDA Drug Labeling

The FDA-approved prescribing information for gabapentin explicitly lists cognitive impairment as an adverse effect:

• "Thinking abnormal" occurs in 3% of postherpetic neuralgia patients (vs 0% placebo) and 2% of epilepsy patients (vs 1% placebo). 1
• Additional cognitive effects include somnolence (19-21%), dizziness (17-28%), ataxia (13%), amnesia (2%), and incoordination (1-2%). 1
• The FDA label warns that gabapentin "can slow your thinking and motor skills" and advises against driving or operating heavy machinery until effects are known. 1

Population-Based Research Evidence

The most recent and highest-quality evidence comes from a 2023 Taiwanese population-based cohort study of 206,802 patients, which found gabapentin/pregabalin exposure significantly increased dementia risk (adjusted hazard ratio 1.45,95% CI 1.36-1.55). 2

Key findings from this study:

• Risk increased in a dose-dependent manner with higher cumulative defined daily doses. 2
• Younger patients (age <50) showed particularly elevated risk (HR 3.16,95% CI 2.23-4.47). 2
• The authors concluded these drugs "should be used with caution, particularly in susceptible individuals." 2

Supporting Evidence in Older Adults

A 2022 retrospective cohort study using the National Alzheimer's Coordinating Center database found gabapentin initiation in cognitively normal older adults (≥65 years) was associated with significant cognitive and functional decline. 3

Specific findings included:

• Worsening Clinical Dementia Rating global score (OR 1.55,95% CI 1.07-2.25). 3
• Increased CDR sum of boxes (OR 1.94,95% CI 1.22-3.09). 3
• Functional status decline measured by FAQ (OR 1.78,95% CI 1.12-2.83). 3
• Increased falls (OR 2.51,95% CI 1.19-5.31) in those without pre-existing motor dysfunction. 3

Context from Perioperative Guidelines

The American Society of Anesthesiologists' 2021 statement on perioperative brain health noted that in a large trial of 697 older surgical patients (mean age 72), gabapentin 900mg did not prevent postoperative delirium and showed no cognitive benefit despite modest opioid reduction. 4

Special Populations at Higher Risk

Patients with pre-existing cognitive impairment appear particularly vulnerable. Two case reports documented psychomotor agitation and heightened anxiety in brain-injured patients within one week of starting gabapentin 900mg daily, with symptoms resolving within 48 hours of discontinuation. 5

Pediatric patients (3-12 years) receiving gabapentin for epilepsy show neuropsychiatric adverse reactions including thought disorder (concentration problems, school performance changes) in 1.7% versus 0% with placebo. 1

Important Caveats

One animal study suggested that maintaining stable gabapentin plasma levels through controlled-release formulations might avoid memory impairment while preserving anticonvulsant effects, though this has not been validated in humans. 6

Another animal study found gabapentin could actually improve spatial memory and reverse cognitive deficits from prenatal tobacco smoke exposure, but these findings have limited applicability to clinical practice. 7

Clinical Implications

The cognitive risks of gabapentin must be weighed against therapeutic benefits, particularly in:

• Older adults (≥65 years), who show measurable cognitive/functional decline even when starting with normal cognition 3
• Patients with pre-existing cognitive impairment or brain injury, who may experience acute agitation 5
• Younger patients requiring long-term therapy, who paradoxically show higher dementia risk 2
• Patients requiring higher cumulative doses, where dementia risk increases proportionally 2

Benzodiazepines should be avoided in older patients and those with cognitive impairment due to decreased cognitive performance, making gabapentin's cognitive effects particularly concerning as an alternative. 4