Does gabapentin (Neurontin) increase the risk of dementia?

Gabapentin and Risk of Dementia

Gabapentin use is associated with an increased risk of dementia, particularly with long-term use and higher doses, and should be used with caution in older adults due to its potential for neurocognitive decline. 1, 2, 3

Evidence on Gabapentin and Cognitive Effects

Recent research provides compelling evidence regarding gabapentin's association with cognitive impairment and dementia:

• A 2022 retrospective cohort study found that gabapentin initiation in cognitively normal older adults was significantly associated with:

  • Cognitive decline at follow-up visits (odds ratio 1.55-1.94)
  • Functional status decline
  • Increased falls (odds ratio 2.51) 1

• A 2023 population-based matched cohort study demonstrated a 45% increased risk of dementia in patients treated with gabapentin or pregabalin (HR 1.45) with higher risk observed with:

  • Increased cumulative doses
  • Younger patients showing even higher relative risk (HR 3.16 for patients <50 years) 2

• A 2025 study specifically examining chronic low back pain patients found:

  • 29% increased risk of dementia with six or more gabapentin prescriptions
  • 85% increased risk of mild cognitive impairment
  • Risk doubled in non-elderly adults (18-64 years)
  • Dose-response relationship with higher prescription frequency correlating with greater risk 3

Mechanism and Risk Factors

The exact mechanism by which gabapentin may contribute to cognitive decline isn't fully established, but several factors may increase risk:

• Higher doses (>600 mg/day) are associated with a 29% increased risk of hospitalization with altered mental status 4
• Cumulative exposure appears to increase risk, with more frequent prescriptions correlating with higher dementia incidence 3
• Older adults are particularly vulnerable to gabapentin's cognitive effects, though younger patients show higher relative risk increases 2

Clinical Implications and Recommendations

1. Dosing considerations:

   • Use the lowest effective dose of gabapentin when prescribed
   • For patients requiring gabapentin (such as those with neuropathic pain), consider starting at ≤600 mg/day to minimize cognitive risk 4

2. Monitoring:

   • Regularly assess cognitive function in patients on gabapentin
   • Be vigilant for early signs of altered mental status, especially in older adults
   • Consider periodic cognitive screening for patients on long-term therapy

3. Risk stratification:

   • Exercise particular caution in patients with:
     • Existing cognitive impairment
     • Multiple prescriptions of gabapentin (≥6)
     • Need for higher doses (>600 mg/day)
     • Concurrent use of other medications affecting cognition

4. Alternative considerations:

   • For neuropathic pain management, consider alternative treatments with potentially lower cognitive risk
   • For pruritus management, consider alternatives like capsaicin cream or topical calcipotriol 5

Special Considerations

While one small study suggested gabapentin might help manage behavioral symptoms in dementia patients with comorbidities 6, the preponderance of evidence indicates cognitive risks that outweigh potential benefits for most patients.

It's worth noting that long-term use of sedative antihistamines has also been associated with dementia risk and should be avoided except in palliative situations 5, suggesting a broader concern about medications with central nervous system effects.

In summary, the evidence strongly suggests gabapentin increases dementia risk, particularly with higher doses and longer duration of use. Clinicians should carefully weigh the benefits against these risks, especially in older adults and those already at risk for cognitive decline.