Treatment for Numbness Due to Peripheral Neuropathy

First-Line Pharmacological Options

The American Academy of Physical Medicine and Rehabilitation recommends pregabalin (300-600 mg/day) as a first-line treatment for peripheral neuropathic pain, acting by binding to the α-2-δ subunit of voltage-gated calcium channels 1
Gabapentin (900-3600 mg/day) is an alternative to pregabalin with similar efficacy but may require more frequent dosing 3
Duloxetine (60-120 mg/day) is effective for diabetic peripheral neuropathy with a number needed to treat of 5.2 for 60 mg/day 2
Tricyclic antidepressants (TCAs) such as amitriptyline (25-75 mg/day) are effective with a number needed to treat of 1.5-3.5, but have more side effects than newer agents 4

Topical lidocaine (5% patches) should be considered for localized peripheral neuropathic pain, particularly with allodynia 2
Topical capsaicin (0.075%) applied sparingly three to four times per day can provide relief for neuropathic pain with minimal systemic effects 3
Topical menthol (1% cream) applied twice daily to the affected area may provide rapid relief of peripheral neuropathy symptoms 5

If first-line medications provide inadequate relief, consider adding another first-line agent from a different class 3
Venlafaxine (150-225 mg/day) is a serotonin-norepinephrine reuptake inhibitor that can be considered if duloxetine is not tolerated 4
Tramadol (200-400 mg/day) can be considered as a second-line treatment with its dual mechanism as a weak μ-opioid agonist and inhibitor of serotonin/norepinephrine reuptake 3

For elderly patients, start with lower doses and titrate more slowly due to increased risk of side effects 2
TCAs should be used with caution in patients with cardiac disease, glaucoma, or orthostatic hypotension 3
Adjust gabapentin and pregabalin doses in patients with renal impairment 2
Duloxetine is contraindicated in patients with hepatic disease 3

Exercise and functional training can help reduce neuropathic symptoms 2
Alpha-lipoic acid (600 mg IV daily for 3 weeks) has shown some efficacy in reducing neuropathic pain in diabetic neuropathy 3

Strong opioids should generally be avoided due to risks of addiction and other adverse effects 2