MKSAP quiz: Worsening foot pain
This month's quiz asks readers to treat a 67-year-old patient with type 2 diabetes and a two-year history of worsening pain in his feet.
A 67-year-old man is evaluated for a 2-year history of worsening pain in his feet. He describes the pain as long-standing aching and burning. The pain is persistent, sometimes waking him from sleep. Medical history is otherwise significant for type 2 diabetes mellitus, hypertension, and hyperlipidemia. Medications are insulin glargine, insulin aspart, valsartan, aspirin, and simvastatin.
On physical examination, vital signs are normal. The feet are insensate to monofilament testing, and vibratory sensation is absent in the feet and ankles. No evidence of skin breakdown is noted.
Which of the following is the most appropriate treatment?
A. Oral duloxetine
B. Oral hydromorphone
C. Oral lamotrigine
D. Oral tramadol
E. Topical diclofenac
MKSAP Answer and Critique
The correct answer is A. Oral duloxetine. This item is available to MKSAP 18 subscribers as item 4 in the General Internal Medicine section. More information about MKSAP 18 is available online.
The most appropriate treatment for this patient with evidence of painful diabetic peripheral neuropathy and substantial neuropathic pain is initiation of oral duloxetine. Diabetes mellitus can cause various types of neuropathy. The most common pattern is symmetric distal sensory or sensorimotor. It is characterized by a stocking-glove distribution that ascends proximally. Diabetic sensorimotor neuropathy frequently presents as a sensation of numbness, tingling, burning, heaviness, pain, or sensitivity to light touch. The pain may worsen at night and with walking. Glycemic control and minimizing cardiovascular risk factors can slow the progression and improve the symptoms of diabetic neuropathy. Treatment of painful neuropathies is symptomatic. Tricyclic antidepressants (amitriptyline, nortriptyline), serotonin-norepinephrine reuptake inhibitors (venlafaxine, duloxetine), antiepileptic drugs (pregabalin, gabapentin, valproic acid), opioids (tapentadol), and topical capsaicin are commonly used. However, only pregabalin, duloxetine, and tapentadol (extended release) have FDA approval for painful diabetic neuropathy. Although duloxetine and gabapentinoids are considered first-line therapy, they are costly. The dosage of duloxetine is started at 20 mg/d or 30 mg/d and increased to a goal dosage of 60 mg/d. Dosages higher than 60 mg/d have not been shown to be more effective for analgesia.
Hydromorphone is a potent opioid agonist that is typically used in the treatment of cancer-associated pain, whereas tramadol is a weak opioid agonist with analgesic activity that is influenced by inhibition of serotonin and norepinephrine reuptake. Although potentially effective in the treatment of neuropathic pain syndromes, opioids are considered third-line therapy after maximization and combination of neuropathic agents. Studies have shown that most patients with peripheral neuropathies are not treated with appropriate neuropathic agents or adequate dosages of these drugs, and dosages should be maximized before initiating opioids.
The effectiveness of lamotrigine for chronic neuropathic pain was evaluated in a systematic review. The studies included patients with central poststroke pain, diabetic neuropathy, HIV-related neuropathy, intractable neuropathic pain, spinal cord injury–related pain, and trigeminal neuralgia. Only one study of patients with HIV-related neuropathy had a statistically significant result, which was restricted to patients receiving antiretroviral therapy. The authors concluded that there is no role for lamotrigine in the treatment of chronic neuropathic pain.
Topical NSAIDs such as diclofenac (available as a solution, spray, gel, or patch) provide similar pain relief for inflammatory conditions as oral medications with fewer gastrointestinal effects. However, they are significantly more expensive than oral NSAIDs. More importantly, anti-inflammatory agents have not been shown to be effective in the treatment of peripheral neuropathies and would not be indicated in this patient with a neuropathic pain syndrome.
Key Point
- Gabapentinoids and serotonin-norepinephrine reuptake inhibitors are first-line therapy for neuropathic pain syndromes.