What is the preferred treatment, gabapentin (Neurontin) or Lyrica (pregabalin), for a patient, particularly an older adult with comorbidities such as diabetes, presenting with neuropathy?

Gabapentin or Pregabalin for Neuropathy

Pregabalin should be the preferred initial choice for neuropathic pain in older adults with comorbidities like diabetes, based on its superior pharmacokinetic profile, easier titration, and comparable efficacy to gabapentin. 1, 2

Why Pregabalin is Preferred

Pregabalin has linear, predictable pharmacokinetics that make dosing more straightforward, especially in older adults and those with renal impairment. 1, 2 In contrast, gabapentin has nonlinear, saturable absorption that complicates dose titration and makes therapeutic effects less predictable. 2

For older adults specifically, pregabalin allows for more rapid and reliable titration to therapeutic doses. 1 Start pregabalin at 25-50 mg/day (use 25 mg if moderate or greater renal impairment exists), then escalate incrementally every few days while monitoring for side effects. 1 The effective dose range is typically 150-600 mg/day in two divided doses, though older adults may respond to lower doses. 1

Pregabalin is FDA-approved specifically for diabetic peripheral neuropathy, while gabapentin is not, though both have strong evidence for efficacy. 3, 2

Efficacy Comparison

Both medications work through the same mechanism (binding α2δ subunits of voltage-gated calcium channels), and both are considered first-line treatments for neuropathic pain. 1, 2

In diabetic neuropathy, pregabalin achieves substantial pain relief (≥50% reduction) in approximately 38% of patients versus 21% with placebo (NNT 5.9). 4 Gabapentin shows similar efficacy at 38% versus 21% placebo (NNT 5.9). 4

In postherpetic neuralgia, pregabalin provides substantial benefit to 32% versus 17% placebo (NNT 6.7), while gabapentin shows 32% versus 17% placebo (NNT 6.7). 4

The American Academy of Physical Medicine and Rehabilitation rates pregabalin as "Level A" (established effective) for diabetic neuropathy, while gabapentin is only "Level B" (probably effective), reflecting stronger evidence quality for pregabalin. 2

Practical Dosing Algorithm

For Pregabalin (Preferred):

• Day 1-3: Start 25-50 mg once daily at bedtime (use 25 mg if age >75, renal impairment, or multiple comorbidities) 1, 2
• Week 1: Increase to 75 mg twice daily if tolerated 2
• Week 2: Increase to 150 mg twice daily (300 mg/day total) - this is the minimum effective dose for most patients 2, 5
• Week 3-4: If pain control inadequate, increase to 300 mg twice daily (600 mg/day maximum effective dose) 2, 5
• Higher doses (>300 mg/day) are not consistently more effective and cause more adverse effects 2

For Gabapentin (Alternative):

• Day 1: 100-200 mg once daily at bedtime (use 100 mg if age >75 or renal impairment) 1, 6
• Day 2: 300 mg twice daily 6
• Day 3: 300 mg three times daily (900 mg/day) 6
• Week 1-2: Titrate to 1800 mg/day in three divided doses 6
• Week 3-4: May increase to 2400-3600 mg/day if needed, though older adults often respond to lower doses 1, 6

Critical Considerations for Older Adults with Diabetes

Both medications require mandatory dose reduction in renal impairment, which is common in diabetic patients. 2, 7 Check creatinine clearance before initiating therapy. 7

In patients with edema or heart failure, use both medications with extreme caution as they can worsen fluid retention. 1 This is particularly important in diabetic patients who often have cardiovascular comorbidities. 1

Common adverse effects (dizziness, somnolence, peripheral edema) occur in 60-70% of patients on either medication, but are typically dose-dependent and can be minimized with slow titration. 1, 4 In older adults, these neurological side effects (dizziness 19%, somnolence 14%, gait disturbance 14%) significantly increase fall risk. 3, 4

Monitor specifically for: balance problems, confusion, lethargy, and tremor - all more frequent in patients ≥65 years. 3

When to Choose Gabapentin Instead

Choose gabapentin over pregabalin if cost is a major barrier, as generic gabapentin is substantially less expensive than pregabalin. 1, 2 However, recognize that the more complex titration schedule may reduce compliance. 2

If a patient fails to respond to pregabalin at adequate doses (300-600 mg/day for 4-8 weeks), switching to gabapentin is unlikely to provide benefit since they share the same mechanism of action. 2 Instead, consider switching to duloxetine 60 mg daily (another FDA-approved first-line agent for diabetic neuropathy) or adding it as combination therapy. 1, 2, 5

Common Pitfalls to Avoid

Never abruptly discontinue either medication - taper gradually over at least one week to avoid withdrawal symptoms including anxiety, insomnia, nausea, and pain exacerbation. 2

Do not use subtherapeutic doses - pregabalin 75 mg/day or gabapentin 300-600 mg/day are insufficient for most patients and lead to treatment failure. 2, 5 The minimum effective pregabalin dose is typically 150 mg/day, and for gabapentin it is 900 mg/day. 1, 6

Avoid combining with opioids or benzodiazepines without careful monitoring, as this significantly increases risk of respiratory depression, especially in older adults. 3

Do not overlook concurrent optimization of glycemic control - this is the only intervention proven to slow neuropathy progression in type 2 diabetes, though it will not reverse existing nerve damage. 1, 5