What are alternative treatments to gabapentin (Neurontin) for neuropathy?

Alternative Treatments to Gabapentin for Neuropathy

For neuropathic pain when gabapentin is not an option, switch to duloxetine 60 mg once daily as the first-line alternative, or consider pregabalin if faster titration and simpler dosing are priorities. 1, 2

First-Line Alternatives

Duloxetine (Preferred SNRI)

• Duloxetine 60 mg once daily is the recommended first alternative to gabapentin, with consistent efficacy demonstrated in diabetic peripheral neuropathy and sustained effectiveness for up to 1 year 3
• Start with 30 mg once daily for 1 week to reduce nausea, then increase to 60 mg once daily; maximum dose is 60 mg twice daily (120 mg/day total) 3, 2
• The Number Needed to Treat (NNT) is 4.9 for 120 mg/day and 5.2 for 60 mg/day to achieve at least 50% pain reduction 3
• Duloxetine provides additional benefits including antidepressant effects and no weight gain, with most common adverse effects being transient nausea, somnolence, dizziness, constipation, and dry mouth 3
• Does not cause clinically important electrocardiographic changes or blood pressure alterations, and aminotransferase monitoring is unnecessary 3

Pregabalin (Alternative Gabapentinoid)

• Pregabalin offers advantages over gabapentin including linear pharmacokinetics, simpler twice-daily dosing, and faster titration to effective doses 1
• Start with 50 mg three times daily or 75 mg twice daily, increase to 300 mg/day after 3-7 days, then by 150 mg/day every 3-7 days as tolerated to maximum 600 mg/day 3
• For elderly patients specifically, start with lower doses of 25-50 mg/day with gradual titration 1
• NNT is 4.04 for 600 mg/day and 5.99 for 300 mg/day in diabetic neuropathy 3
• Higher doses of pregabalin (up to 600 mg/day) result in significantly greater pain relief; many patients who don't respond to lower doses will respond when the dose is escalated 4
• Most frequent side effects are dizziness, somnolence, peripheral edema, headache, and weight gain 3
• Note that pregabalin is a Schedule V controlled substance 1

Venlafaxine (Alternative SNRI)

• Effective in painful diabetic neuropathy and painful polyneuropathies of different origins (but not postherpetic neuralgia) 3
• Start with 37.5 mg once or twice daily, increase by 75 mg each week to target dose of 150-225 mg/day 3
• Requires 2-4 weeks to titrate to efficacious dosage; available in short- and long-acting preparations 3
• Use with caution in patients with cardiac disease due to potential cardiac conduction abnormalities and blood pressure increases 3
• Must be tapered when discontinuing due to withdrawal syndrome 3

Second-Line Alternatives

Tricyclic Antidepressants (TCAs)

• Secondary-amine TCAs (nortriptyline or desipramine) are preferred over tertiary-amine TCAs due to better tolerability 3
• Start with 25 mg at bedtime, increase by 25 mg every 3-7 days as tolerated to maximum 150 mg/day 3
• Requires 6-8 weeks for adequate trial, including 2 weeks at highest tolerated dose 3
• Use with extreme caution in elderly patients and those with cardiovascular disease, orthostatic hypotension, or urinary retention 1, 2
• Obtain screening electrocardiogram for patients older than 40 years; avoid if PR or QTc interval is prolonged 3
• Doses >100 mg/day are associated with increased risk of sudden cardiac death 3

Topical Treatments

Lidocaine 5% Patch

• Apply maximum of 3 patches daily for maximum of 12-18 hours 3
• Requires 3-week trial to assess efficacy 3
• Excellent tolerability in elderly patients, particularly useful for focal neuropathic pain 1

Capsaicin 8% Patch

• Strongly recommended as adjunctive or alternative therapy, with single 30-minute application providing pain relief for ≥12 weeks 2
• Apply 4% lidocaine for 60 minutes before capsaicin application, then wipe off to reduce application-site pain 2

Critical Prescribing Considerations

Dosing Thresholds

• Do not continue escalating gabapentin beyond 3600 mg/day, as there is no evidence of additional benefit and adverse effects increase 2
• For duloxetine, 60 mg once daily appears as effective as 60 mg twice daily 3
• Never abruptly discontinue gabapentin; taper gradually over minimum 1 week (reduce by 10% of original dose per week) to avoid withdrawal symptoms 2

What NOT to Use

• Do not use lamotrigine, as it is specifically recommended against for neuropathic pain due to lack of efficacy and risk of serious rash 2
• Avoid first-generation anticonvulsants (carbamazepine, phenytoin) due to limited evidence and high frequency of adverse events 3
• Mexiletine provides only modest analgesic effect and requires regular electrocardiogram monitoring, limiting long-term use 3

Renal Dosing Adjustments

• Both gabapentin and pregabalin require dose reduction in patients with renal insufficiency (creatinine clearance <60 mL/min) 3, 5

Adjunctive Non-Pharmacologic Interventions

• Cognitive behavioral therapy is strongly recommended alongside medication adjustments 2
• Physical and occupational therapy are also strongly recommended 2
• Hypnosis specifically for neuropathic pain carries a strong recommendation 2