Table 1. Drugs with Class I or II evidence of efficacy in neuropathic pain associated with diabetic sensory polyneuropathya.

Drug	Mechanism of action	Dosage	Adverse effects	Comments
Anticonvulsants
Gabapentin	Unknown, but affects the synthesis and release of GABA and alters the release of monoamine neurotransmitters and blood serotonin levels	900–3,600 mg/d in 3 divided doses	Somnolence, dizziness, weight gain, occasionally peripheral edema	Dosage must be adjusted in renal impairment
Pregabalin	Binds to calcium channels and inhibits the release of excitatory neurotransmitters	150–300 mg/d in 2–3 divided doses	Somnolence, dizziness, weight gain	Dosage must be adjusted in renal impairment. Linear pharmacokinetics
Sodium valproate	Unknown. The drug is a histone deacetylase inhibitor that inhibits GABA transmission and blocks voltage-gated sodium channels and T-type calcium channels	500–1,000 mg/d in 2 divided doses	Headache, somnolence, dizziness, abdominal pain, tremor	Pregnancy category D. Monitor CBC and BMP
Antidepressants
Venlafaxine	Inhibits the reuptake of serotonin and norepinephrine	150–225 mg/d in 2–3 divided doses	Nausea, somnolence, headache	Risk of serotonin syndrome with concurrent use of MAO inhibitors
Duloxetine	Balanced reuptake inhibition of serotonin and norepinephrine	60 mg 1–2 times a day	Somnolence, headache, dizziness, nausea	Risk of serotonin syndrome with concurrent use of MAO inhibitors. Not recommended for use with TCAs or in patients with end-stage renal disease or hepatic impairment
Amitriptyline	Inhibits the reuptake of serotonin and norepinephrine	25–100 mg nightly	Anticholinergic effects, sedation, cardiac conduction changes, orthostatic hypotension	Risk of serotonin syndrome with concurrent use of MAO inhibitors. Use with caution in elderly patients
Other Capsaicin	Depletes substance P from nerve endings	0.075% cream, applied 3–4 times daily	Transient sensation of warmth or burning	Patients should wear gloves and wash hands after application
Tramadol	Centrally acting analgesic with monoaminergic and opioid mechanisms	50–100 mg every 4–6 h	Dizziness, headache, somnolence; can lower seizure threshold	A withdrawal syndrome can occur with abrupt discontinuation. Avoid use with serotonergic agents
Alpha-lipoic acid	Antioxidant	600 mg 1–2 times per day	Nausea, vomiting, rash	Use with caution in patients who may be predisposed to hypoglycemia

^aThis list of treatments is not exhaustive. Other options are discussed in the text.

BMP basic metabolic profile; CBC complete blood count; GABA gamma-aminobutyric acid; MAO monamine oxidase; TCA tricyclic antidepressant