Is there a study linking gabapentin to an increased risk of dementia?

Gabapentin and Dementia Risk: Evidence from Recent Research

The most recent and highest quality evidence indicates that gabapentin use is significantly associated with an increased risk of dementia, with a hazard ratio of 1.45 (95% CI, 1.36-1.55) compared to non-users. 1

Key Research Findings

Primary Evidence on Gabapentin and Cognitive Impairment

• A 2023 population-based matched cohort study using Taiwan's National Health Insurance Research Database found that patients treated with gabapentin or pregabalin had a 45% higher risk of developing dementia compared to matched non-users 1
• The risk increased with higher cumulative defined daily doses, establishing a dose-response relationship
• Notably, the risk was particularly elevated in younger patients (age <50) with a hazard ratio of 3.16 (95% CI, 2.23-4.47) 1

Supporting Evidence

• A 2022 study using the National Alzheimer's Coordinating Center data found that gabapentin initiation in cognitively normal older adults was associated with:

  • Cognitive decline at follow-up visits (OR 1.55 [95% CI 1.07,2.25])
  • Functional status decline
  • Increased falls at subsequent visits (OR 2.51 [95% CI 1.19,5.31]) 2

• A 2018 population-based study found that high-dose gabapentin (>600 mg/day) was associated with a 29% increased risk of hospitalization with altered mental status within 30 days compared to low-dose regimens (≤600 mg/day) 3

Mechanisms and Risk Factors

The cognitive effects of gabapentin may be related to:

• Inhibition of α2δ subunits of presynaptic voltage-gated calcium channels, which affects neurotransmitter release 4
• Potential interactions with sodium-glucose cotransporters in the brain, which play a role in neuronal glucose sensing and survival 5
• Cumulative dose effects, with higher doses associated with greater risk 1
• Age-related factors, though interestingly the relative risk appears higher in younger patients 1

Clinical Implications and Recommendations

For Neuropathic Pain Management

• Consider duloxetine as an FDA-approved alternative with fewer cognitive concerns for neuropathic pain 6
• If gabapentin is necessary:
  • Use the lowest effective dose (starting at 100-300 mg daily)
  • Monitor cognitive function regularly
  • Be vigilant for early signs of altered mental status, which may appear within 30 days of initiation 3

For Patients at Risk of Cognitive Impairment

• Avoid gabapentin in patients with pre-existing cognitive impairment when possible
• For patients requiring gabapentin who are at risk:
  • Implement regular cognitive assessments
  • Consider shorter treatment durations
  • Avoid concomitant use with other CNS depressants 6

Limitations and Caveats

• Most studies are observational, which limits causal inference
• The cognitive effects may be reversible upon discontinuation, though this requires further study
• Benefit-risk assessment is still necessary, as untreated neuropathic pain can also negatively impact quality of life and cognitive function

Conclusion

The evidence strongly suggests that gabapentin use is associated with an increased risk of cognitive impairment and dementia. When prescribing gabapentin, clinicians should carefully weigh the benefits against these risks, particularly in patients who may be vulnerable to cognitive decline.