A 72-year-old man with a seven-year history of type 2 diabetes mellitus comes to the physician because of pain in his feet. He has had numbness and tingling in his feet up to his ankles for two years. He recently began experiencing burning pain in both feet that extends to the mid-calf. This discomfort keeps him awake at night. He has no associated weakness. He has tried capsaicin ointment without relief.
On examination, there is decreased sensation to light touch and pinprick involving both feet. Ankle jerk reflex is absent bilaterally. Muscle strength in both lower extremities is normal with normal pulses. The remainder of the examination is within normal limits.
Laboratory data reveals a normal complete blood count, TSH, protein electrophoresis, and vitamin B₁₂ levels. His HbA1c is 7.5%.
Which of the following would be the best initial therapeutic option for this patient?

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11ec193a_97b2_aed6_853d_19bca08e5675_MD0002_00 This patient's presentation is consistent with painful diabetic neuropathy, a usually symmetrical sensory neuropathy that affects the distal lower extremities. Nearly 20% of patients have nerve damage at the time of diabetes diagnosis, indicating that pre-diabetes may be associated with early neuropathy. Patients may be asymptomatic or present with loss of vibratory sensation and proprioception, pain in the extremities, and decreased or absent ankle reflexes. As the disease progresses, patients may develop more widespread loss of reflexes and motor weakness. Tight glucose control helps prevent neuropathy, but it may not effectively help existing neuropathy. Pregabalin is effective in decreasing pain in diabetic neuropathy, and side effects (e.g., dizziness, somnolence, and confusion) are seen mainly at high doses. This elderly patient's neuropathy increases his risk for falls and injury. Low-dose pregabalin with careful monitoring for adverse effects offers the best initial treatment with a low side effect profile for this patient. Since there is conflicting evidence regarding the efficacy of gabapentin in treating diabetic peripheral neuropathy, its use is controversial. (Choice A) Tricyclic antidepressants (TCAs) are usually preferred in younger patients for diabetic neuropathy. Older patients can experience significant anticholinergic side effects (e.g., dry mouth, urinary retention, and constipation). Tricyclic antidepressant agents may also have more cardiac toxicity and induce the syndrome of inappropriate antidiuretic hormone more frequently in older patients. (Choice B) Carbamazepine is an anticonvulsant that can be effective in treating painful neuropathy, but it is usually a second-line therapy. (Choice C) Naproxen and other NSAIDS can relieve musculoskeletal or joint pain resulting from long-standing neuropathy, but they may have more side effects (e.g., renal, GI, cardiac) in older patients. (Choice D) Oxycodone and other opiates are not first-line therapies for painful diabetic neuropathy, especially in the older population where the benefits are outweighed by potential side effects (e.g., nausea, constipation, headache, and somnolence). Educational objective: Pregabalin is an effective first-line agent in elderly patients for diabetic neuropathy. In older patients, opiates and agents with strong anticholinergic effects should be avoided as initial therapy due to potential adverse effects. __________ References: Efficacy, safety and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized controlled trials across a range of doses. (http://www.ncbi.nlm.nih.gov/pubmed/18356405) Effects of desipramine, amitriptyline and fluoxetine on pain in diabetic neuropathy. (http://www.ncbi.nlm.nih.gov/pubmed/1560801) Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. (http://www.ncbi.nlm.nih.gov/pubmed/21482920)

A 72-Year-Old Man with a Seven-Year History of Type 2