Is gabapentin (Neurontin) safe to use in patients at risk for Alzheimer's disease?

Gabapentin and Alzheimer's Risk

Gabapentin should be used with caution in patients at risk for Alzheimer's disease due to evidence showing an increased risk of cognitive decline and dementia with its use. 1, 2

Evidence on Gabapentin and Cognitive Function

Recent research provides concerning evidence about gabapentin's effects on cognition:

• 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 [1.07,2.25])
  • Worsening on Clinical Dementia Rating scales
  • Functional status decline
  • Increased falls at later follow-up visits (odds ratio: 2.51 [1.19,5.31]) 1

• A 2023 large population-based study from Taiwan demonstrated that patients treated with gabapentin or pregabalin had a 45% increased risk of developing dementia (hazard ratio: 1.45 [1.36-1.55]) compared to matched controls 2

  • This risk was dose-dependent, increasing with higher cumulative doses
  • The risk was particularly pronounced in younger patients (age <50)

Risk-Benefit Assessment for Patients at Risk for Alzheimer's

When considering gabapentin for patients at risk for Alzheimer's disease:

1. Primary indications for gabapentin:

   • Approved for seizure disorders and postherpetic neuralgia
   • Commonly used off-label for neuropathic pain and restless legs syndrome

2. Alternative medications to consider:

   • For restless legs syndrome: The American Academy of Sleep Medicine suggests using gabapentin only in specific populations such as those with end-stage renal disease 3
   • For neuropathic pain: Consider other agents with less cognitive impact

3. Medication management principles:

   • Patients with Alzheimer's disease or at risk are particularly vulnerable to adverse effects of polypharmacy 4
   • Anticholinergic medications should be strictly avoided in these patients 4
   • While gabapentin is not anticholinergic, its cognitive effects warrant caution

Monitoring and Management Recommendations

If gabapentin must be used in patients at risk for Alzheimer's disease:

1. Baseline cognitive assessment before initiating therapy
2. Regular cognitive monitoring during treatment using standardized tools
3. Start at low doses and titrate slowly
4. Set clear therapeutic goals and discontinue if not achieved
5. Consider discontinuation if any cognitive decline is observed
6. Evaluate for falls risk as gabapentin increases fall risk in older adults

Special Considerations

• Behavioral symptoms in dementia: While some case reports suggest gabapentin may help manage behavioral and psychological symptoms of dementia (BPSD), evidence is limited to case reports and small case series with no controlled studies 5, 6

• Comorbidities: Gabapentin may be considered in patients with dementia who have specific comorbidities like epilepsy or severe neuropathic pain where benefits might outweigh risks 7

• Duration of therapy: Short-term use may carry less risk than long-term exposure, but even short-term use has been associated with cognitive changes 1

The decision to use gabapentin in patients at risk for Alzheimer's disease should carefully weigh the potential benefits against the documented risks of cognitive decline and increased dementia risk, with strong consideration of alternative therapies whenever possible.