Can gabapentin (anticonvulsant medication) cause cognitive decline?

Gabapentin and Cognitive Decline

Gabapentin can cause cognitive decline, particularly in older adults, and should be used with caution due to its potential negative effects on cognition. 1, 2

Evidence for Cognitive Effects

Gabapentin has been associated with cognitive impairment through several mechanisms:

• The FDA drug label explicitly warns about central nervous system effects, including "thought disorder," "concentration problems," and "changes in school performance" 2
• Recent evidence from a 2022 study found that gabapentin initiation in older adults with normal cognition was significantly associated with cognitive decline, functional status decline, and increased falls 3
• A 2023 population-based cohort study demonstrated that patients treated with gabapentin had a 45% increased risk of developing dementia, with higher risk at greater cumulative doses 4

Risk Factors for Cognitive Impairment

Several factors increase the likelihood of experiencing cognitive side effects:

• Age: Older adults are particularly vulnerable to gabapentin-associated cognitive impairment 1
• Dosage: Higher doses correlate with greater risk of cognitive effects 1
• Concomitant medications: Use with other CNS depressants or anticholinergic medications significantly increases cognitive impairment risk 1
• Pre-existing cognitive vulnerability: Patients with existing cognitive issues are at higher risk 1

Clinical Recommendations

1. Dosing considerations:

   • Use the lowest effective dose possible, preferably ≤600 mg/day 1
   • Titrate slowly in older adults or those with cognitive concerns

2. Monitoring:

   • Perform baseline cognitive assessment before initiating therapy
   • Conduct regular cognitive assessments, especially within the first 30 days of treatment 1
   • Watch for early signs of cognitive changes including confusion, memory problems, or difficulty concentrating

3. Patient education:

   • Inform patients about potential cognitive side effects
   • Advise patients to report any changes in thinking, memory, or concentration

Special Considerations

In patients with liver disease, gabapentin should be used with particular caution as it may exacerbate cognitive issues. The AASLD practice guidance notes that gabapentin has synergistic effects with other sedating medications and should be minimized or avoided in patients with altered mental status 5.

Alternative Therapies

For patients experiencing cognitive side effects or at high risk:

• For neuropathic pain: Consider duloxetine or amitriptyline (noting that amitriptyline has its own anticholinergic side effect profile) 1
• For REM sleep behavior disorder: Melatonin (3-12 mg) may be an alternative with fewer cognitive effects 1

Conflicting Evidence

While most evidence points to cognitive concerns, some older studies show mixed results:

• A 1997 study in epilepsy patients found gabapentin had no measurable effect on cognition at lower doses but did produce sedation at higher doses (2400 mg/day) 6
• However, more recent and comprehensive studies demonstrate significant associations between gabapentin use and cognitive decline 3, 4

The weight of current evidence, particularly from recent studies with larger sample sizes and longer follow-up periods, strongly supports the association between gabapentin and cognitive decline, especially in vulnerable populations like older adults.