Selective serotonin reuptake inhibitors (SSRIs) and other types of antidepressents have demonstrated varying efficacy for diabetic neuropathy, and have generally been found to be less effective than TCAs. Bupropion is an option for neuropathic pain relief. Initial doses start at 100 mg per day, and should be increased 100 mg per week, up to a maximum dose of 200 mg twice daily (400 mg per day).7

Other treatments

The FDA approved the anticonvulsant pregabalin (Lyrica, Pfizer) for diabetic neuropathic pain in 2005, after results from clinical trials indicated that 150 mg to 300 mg daily pregabalin reduced pain scores 50% compared with baseline.8 Common adverse events included dizziness, somnolence, edema and weight gain. Higher doses produced greater pain relief scores, but also carry a risk for dose-dependent adverse events.


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Capsaicin, a topical treatment without systemic side effects, has been shown to be effective, but clinicians must spend time educating patients about application techniques. The drug must be applied three to four times per day for six to eight weeks to achieve symptom improvement. Adverse events include a temporary burning sensation that diminishes with prolonged use but is often intolerable for patients with diabetic neuropathy.9

IV α-lipoic acid infusions at 600 mg per day may also reduce neuropathic symptoms after about three weeks. Results from the SYNDEY 2 trial indicated that an 600 mg daily oral formulation administered in four doses also produced good results among patients with distal symmetric polyneuropathy after five weeks.10

Acetaminophen and ibuprofen do not effectively manage nerve pain in most cases. Because of their risk of promoting gastrointestinal bleeding, clinicians should limit use to short-term adjuvant therapy in patients with a reduced risk of kidney and GI dysfunction.

Because of the risks of dependency and constipation, clinicians should reserve opioids such as oxycodone and tramadol for controlling diabetic neuropathic pain only in the most severe cases.

Electrical nerve stimulation

Transcutaneous electrical nerve stimulation (TENS), a widely used pain therapy that consists of applying mild electrical currents to painful areas using surface electrodes, may have a limited role in managing diabetic neuropathy, according to a recent guideline from the American Academy of Neurology.