What medications are used to treat neuropathy?

Medications for Neuropathic Pain

First-line medications for neuropathic pain include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, calcium channel α2-δ ligands (pregabalin and gabapentin), and topical lidocaine for localized peripheral neuropathic pain. 1

First-Line Medications

Calcium Channel α2-δ Ligands

• Pregabalin is FDA-approved for management of neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and spinal cord injury 2
• Gabapentin is effective for postherpetic neuralgia and painful diabetic neuropathy, with approximately 38% of patients achieving at least 50% pain relief compared to 21% with placebo 3
• For gabapentin, treatment should start at 900 mg/day (300 mg on day 1,600 mg on day 2,900 mg on day 3) with titration to 1800 mg/day for better efficacy; doses up to 3600 mg/day may be needed in some patients 4
• A "low and slow" dosing approach is recommended for pregabalin to limit common side effects and optimize tolerability 5

Antidepressants

• Tricyclic antidepressants (TCAs) like nortriptyline and desipramine are effective first-line options for neuropathic pain 1
• Secondary amine TCAs (nortriptyline, desipramine) are preferred over tertiary amines (amitriptyline, imipramine) due to fewer anticholinergic side effects 6
• TCAs should be used with caution in patients with cardiac disease, with recommended dosages less than 100 mg/day and screening ECG for patients over 40 years 1
• Serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine (60-120 mg/day) and venlafaxine (150-225 mg/day) have fewer anticholinergic effects than TCAs 1
• Duloxetine is particularly effective for diabetic peripheral neuropathy with a number needed to treat of 5.2 at 60 mg/day 1

Topical Agents

• 5% lidocaine patches are recommended for localized peripheral neuropathic pain, particularly with allodynia 1
• High-concentration capsaicin has moderate-quality evidence for postherpetic neuralgia 1

Second-Line Medications

• Tramadol is recommended as a second-line treatment with dual mechanism (weak μ-opioid agonist and inhibits serotonin/norepinephrine reuptake) 1
• Opioid analgesics may be used for acute neuropathic pain, neuropathic cancer pain, or episodic exacerbations of severe pain 6
• Tramadol should be started at 50 mg once or twice daily, with a maximum dose of 400 mg/day, and lower doses in older adults and those with renal/hepatic dysfunction 1

Special Considerations for Different Types of Neuropathic Pain

• Medications with established efficacy in diabetic peripheral neuropathy and postherpetic neuralgia may not be effective in other types of neuropathic pain 6
• HIV-associated neuropathy, chemotherapy-induced neuropathy, and lumbosacral radiculopathy may be relatively refractory to first-line treatments 6
• Chemotherapy-induced peripheral neuropathy has shown no evidence of efficacy with nortriptyline, amitriptyline, or gabapentin in randomized controlled trials 6
• Patients with failed back surgery syndrome may respond to spinal cord stimulation when medications are ineffective 6

Treatment Algorithm

1. Initial Assessment and First-Line Treatment:

   • For localized peripheral neuropathic pain: Consider topical lidocaine or capsaicin 1
   • For diffuse neuropathic pain: Start with either a TCA, SNRI, or gabapentinoid (pregabalin or gabapentin) 6, 1

2. Monitoring and Adjustment:

   • If substantial pain relief (≥50% reduction) is achieved with tolerable side effects, continue treatment 6
   • If partial pain relief is achieved, add another first-line medication from a different class 6
   • If inadequate pain relief (<30% reduction) after an adequate trial, switch to an alternative first-line medication 6

3. Second-Line Approach:

   • If trials of first-line medications alone and in combination fail, consider tramadol or opioid analgesics 6, 1
   • For refractory cases, consider referral to a pain specialist or multidisciplinary pain center 6

Common Side Effects and Precautions

• Gabapentinoids (pregabalin and gabapentin) commonly cause dizziness, somnolence, peripheral edema, and gait disturbance 3
• TCAs can cause anticholinergic adverse effects including dry mouth, orthostatic hypotension, constipation, and urinary retention 6
• Cardiac toxicity is a concern with TCAs, requiring caution in patients with cardiac disease 6
• Dose adjustment is necessary for gabapentinoids in patients with renal impairment 1
• Lower starting doses and slower titration are recommended for older adults 1