Version July 2025
| Medication | Dosage and administration in adults | Avoid or use caution in: | Common adverse effects |
| Preferred agents for most patients | |||
| Gabapentin* | IR: Start with 100 to 300 mg orally 1 to 3 times daily. Can increase gradually to 800 mg 3 times daily (2400 mg daily in 2 or 3 divided doses). ER: Start with 300 mg orally once daily at bedtime. Can increase gradually to 900 mg to 2400 mg once daily. |
| Neurologic: Dizziness, drowsiness, ataxia, confusion. Gastrointestinal: Nausea, diarrhea. Other: Weight gain, peripheral edema, risk for misuse and addiction. |
| Pregabalin* | IR: Start with 25 to 75 mg orally twice daily. Can increase gradually to 75 to 150 mg orally twice daily. ER: Start with 165 mg orally once daily. Can increase gradually to 330 mg orally once daily. |
| Neurologic: Dizziness, drowsiness, ataxia, confusion. Gastrointestinal: Nausea, diarrhea. Other: Weight gain, peripheral edema, risk for misuse and addiction. |
| Duloxetine | Start with 30 mg orally once daily for one week. Can increase to 120 mg orally once daily thereafter. |
| Neurologic: Insomnia, dizziness, fatigue. Gastrointestinal: Nausea, dry mouth, constipation. Other: Sexual dysfunction. |
| Tricyclic antidepressants (amitriptyline; nortriptyline)¶ | Start with 10 to 25 mg orally daily at bedtime. Can increase gradually to 75 to 100 mg orally once daily at bedtime. |
| Antihistaminic: Dizziness, drowsiness, confusion, increased appetite. Anticholinergic: Dry mouth, constipation, urinary retention, blurred vision. Cardiovascular: Orthostatic hypotension, prolonged QT interval, cardiac arrhythmias. Other: Sexual dysfunction, dangerous in overdose. |
| Alternative agents for patients who would like to avoid oral medicationsΔ | |||
| Capsaicin patch 8% NOTE: Administered by health care provider in a clinical setting and monitored for up to 2 hours after treatment | Apply patch to most painful areas of the feet for 30 minutes. Up to 4 patches may be applied in a single application. Treatment may be repeated every 3 months as needed for return of pain (do not apply more frequently than every 3 months). Area should be pretreated with a topical anesthetic prior to patch application. |
| Application site burning, pain, erythema, pruritus. Local pain and irritation may be intolerable. |
| Lidocaine patch 5% | Apply 1 to 3 patches to most painful areas of the feet for 12 hours. Remove for a period of 12 hours before reapplication. |
| Mild to moderate irritation at application site. |
| Other alternative agents | |||
| Tramadol | Start with 37.5 mg orally every 6 hours, as needed for breakthrough pain. |
| Side-effects are similar to other opioids including risks of overdose and opioid use disorder. Added risk of seizures due to drug interactions. |
ER: extended release; HIV-DSPN: human immunodeficiency virus-associated distal symmetric polyneuropathy; IR: immediate release.
* Requires dose adjustment in kidney impairment; refer to drug monographs included within UpToDate.
¶ Nortriptyline is less sedating and has fewer anticholinergic side effects than amitriptyline.
Δ Also used in combination with oral therapies for reducing medication load or as an alternative for patients with contraindications to systemic therapies.