Recommended Adjunctive Treatments for Neuropathic Pain

First-Line Pharmacological Options

The American Diabetes Association recommends pregabalin, duloxetine, and gabapentin as first-line adjunctive treatments for neuropathic pain, with topical lidocaine recommended for localized peripheral neuropathic pain 1, 2, 3
Duloxetine (60-120 mg/day) is FDA-approved for diabetic peripheral neuropathy and shows consistent efficacy, with a strength of evidence supported by the American College of Physicians 1, 3
Tricyclic antidepressants (TCAs) such as amitriptyline or nortriptyline (25-75 mg/day) are effective with an NNT of 1.5-3.5, as recommended by the American Academy of Neurology 6
The American Geriatrics Society recommends starting TCAs at low doses (10 mg/day) in older adults and titrating carefully due to anticholinergic side effects 4, 6

The National Kidney Foundation recommends reducing doses of gabapentin and pregabalin in patients with renal impairment, and considering topical lidocaine as first choice 5
The American Geriatrics Society recommends starting with lower doses and titrating more slowly in older adults, and being vigilant for side effects 4, 5
The American Heart Association recommends using TCAs with caution in patients with cardiovascular disease, and monitoring ECG if necessary 3, 6

The American Academy of Neurology notes that duloxetine can cause nausea, dizziness, somnolence, and constipation, and recommends taking it with food to reduce gastrointestinal side effects 1
The American College of Physicians notes that TCAs can cause dry mouth, orthostatic hypotension, constipation, and urinary retention, and recommends using secondary amine TCAs (nortriptyline, desipramine) for fewer anticholinergic effects 3, 6