Should I, as a middle‑aged adult taking gabapentin for mild‑to‑moderate periodic limb movement disorder, continue the medication given recent research linking gabapentin to a modest increase in cognitive decline?

Should You Continue Gabapentin for Mild-to-Moderate PLMD Given Cognitive Decline Concerns?

Yes, continue gabapentin for your periodic limb movement disorder (PLMD), but optimize your dose and monitor cognitive function closely—the evidence supporting gabapentin's efficacy for PLMD is stronger than the single observational study linking it to cognitive decline in older adults, and PLMD itself causes significant sleep disruption that impairs daytime cognition and quality of life. 1, 2

Understanding the Cognitive Decline Evidence

The recent research you're referencing found that gabapentin initiation was associated with modest increases in cognitive decline measures (Clinical Dementia Rating scores) and falls in older adults who were initially cognitively normal 2. However, this was a retrospective observational study with important limitations:

• The study population consisted of adults aged ≥65 years (mean age 78.7 years), and the indication for gabapentin use was not specified—many were likely taking it for chronic pain conditions rather than PLMD 2
• The cognitive changes were statistically significant but clinically modest, and the study could not establish causation 2
• Critically, untreated sleep disorders like PLMD themselves cause cognitive impairment, daytime dysfunction, and increased fall risk—the study did not account for whether gabapentin was treating an underlying sleep disorder that would independently worsen cognition if left untreated 1

Why Gabapentin Remains Appropriate for PLMD

Gabapentin and its prodrug gabapentin enacarbil are strongly recommended as first-line therapy for restless legs syndrome (RLS) by the American Academy of Sleep Medicine, with moderate certainty of evidence 1, 3. While PLMD is distinct from RLS, they share pathophysiology and treatment approaches:

• Gabapentin significantly reduces periodic limb movements with arousal (PLMA) per hour of sleep and improves sleep quality in controlled trials 4, 5
• In a randomized crossover polysomnography study, gabapentin enacarbil 1200 mg reduced wake time during sleep by 26 minutes and reduced PLMA by 3.1 events per hour compared to placebo 5
• Gabapentin 300-1200 mg (mean 800 mg) demonstrated similar efficacy to ropinirole for reducing PLMS and improving symptoms in a 4-week trial 4

The Critical Trade-Off: Untreated PLMD vs. Medication Risk

Untreated PLMD causes chronic sleep fragmentation, which directly impairs cognitive function, increases fall risk, and reduces quality of life—the very outcomes you're trying to avoid 1. The cognitive effects of chronic sleep deprivation may exceed the modest cognitive risk suggested by the observational gabapentin study 2.

Practical Management Algorithm

1. Optimize Your Current Gabapentin Regimen

• Ensure you're on the lowest effective dose: For mild-to-moderate PLMD, start with 300 mg at bedtime and titrate only if symptoms persist 1, 4
• The mean effective dose in clinical trials was 800 mg (range 300-1200 mg), significantly lower than doses used for chronic pain 4
• Avoid excessive dosing: Higher doses increase sedation and cognitive side effects without proportional benefit for PLMD 1

2. Address Iron Status First

• Check morning fasting serum ferritin and transferrin saturation after avoiding iron supplements for ≥24 hours 1
• If ferritin ≤75 ng/mL or transferrin saturation <20%, add iron supplementation—this may reduce or eliminate the need for gabapentin 1
• Iron deficiency is a reversible cause of PLMD and should be corrected before escalating medication doses 1

3. Implement Cognitive Monitoring

• Establish baseline cognitive function with a simple screening tool (e.g., Montreal Cognitive Assessment) 6
• Reassess cognitive function every 6-12 months while on gabapentin 1
• If you notice new cognitive difficulties, daytime sedation, or increased falls, reduce the gabapentin dose or consider alternative treatments 2

4. Consider Non-Pharmacological Adjuncts

• Cognitive-behavioral therapy (CBT) for insomnia improved sleep quality comparably to clonazepam in PLMD patients and reduced daytime napping 7
• Eliminate exacerbating factors: avoid caffeine, alcohol, and nicotine close to bedtime; ensure regular sleep-wake schedules 1
• These strategies may allow you to use lower gabapentin doses 1, 7

When to Consider Alternatives

Switch away from gabapentin only if:

• You develop clear cognitive decline or functional impairment temporally related to gabapentin initiation 2
• You experience intolerable side effects (dizziness, somnolence) despite dose reduction 5
• Your PLMD symptoms are not adequately controlled on optimized gabapentin therapy 1

Alternative options include:

• Pregabalin: Another alpha-2-delta ligand with twice-daily dosing and potentially superior bioavailability, though it carries similar cognitive concerns 1
• Clonazepam 0.5-1 mg at bedtime: Improves subjective sleep quality and reduces sleep fragmentation, though it does not reduce PLMS index and carries benzodiazepine-related cognitive risks in older adults 6, 8
• Iron supplementation alone if ferritin is low 1

Critical Pitfalls to Avoid

• Do not discontinue gabapentin abruptly based solely on observational data without considering the cognitive and functional consequences of untreated PLMD 1, 2
• Do not assume all cognitive changes are medication-related—PLMD itself causes daytime cognitive impairment through chronic sleep fragmentation 1
• Do not use dopamine agonists (pramipexole, ropinirole) as alternatives—they carry high risk of augmentation (paradoxical worsening) and are no longer recommended as first-line therapy 1
• Do not ignore iron status—correcting iron deficiency may eliminate the need for any medication 1

Bottom Line

For a middle-aged adult with mild-to-moderate PLMD, the benefits of continuing gabapentin at the lowest effective dose outweigh the modest cognitive risks suggested by a single observational study, especially when untreated PLMD itself impairs cognition through chronic sleep disruption. 1, 2 Optimize your dose, correct any iron deficiency, monitor cognitive function regularly, and maintain open communication with your physician about any concerning changes. The goal is to balance effective PLMD treatment with vigilance for medication-related adverse effects.