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What is the best treatment for diabetic neuropathy?

The Journal of Family Practice. 2004 May;53(5):401-419
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Studies involving topical agents are also limited. According to an information summary,3 a total of 4 trials have addressed the efficacy of topical capsaicin for neuropathic pain. Compared with placebo, capsaicin reduces pain (NNT=4; 95% CI, 2.9–6.7), but no pooled information is available on side effects or rate of study withdrawal. Finally, 1 case series has suggested that lidocaine patches are efficacious for diabetic neuropathy.4

A variety of other interventions have been reported for diabetic neuropathy, including non-steroidal anti-inflammatory drugs, transcutaneous electrical nerve stimulation (TENS), angiotensin-converting enzyme inhibitors, and Tramadol, but there have been no published systematic evaluations of them.

The Table characterizes the agents, the number of trials that address each, the NNT, NNH, typical effective dose, and approximate retail cost per month with the average effective dose.

TABLE
Efficacy of drug treatments for diabetic neuropathy

DrugNumber of controlled trialsNNT (95% CI) for 50% pain reductionNNH (95% CI)Efficacious doseTypical cost
Antidepressants163.4 (2.6–4.7)2.7 (2.1–3.9)  
Tricyclics83.5 (2.5–5.6)3.2 (2.3–5.2)Amitryptiline 50–100 mg/d; Nortryptiline 50–75 mg/d$12
SSRIs3Not efficacious N/AN/A
Anticonvulsants*32.7 (2.2–3.8)2.7 (2.2–3.4)  
Phenytoin1Not available3.2 (2.1–6.3)300 mg/d$18
Carbamezapine1Not availableNot available400 mg 2x daily$28
Gabapentin2Not available2.6 (2.1–3.3)600–900 mg 3x daily$333
Valproate1Not availableRare400 mg 3x daily$36
Topical capsaicin44 (2.9–6.7)Not available0.075% 4x daily$39
Lidocaine patch0Not availableNot available1 patch each foot, daily$272
Costs based on 30 days of typical efficacious dose. Retail prices from www.drugstore.com, December 2003, except for capsaicin, which was obtained from Walmart.
*This summary does not include results from Kochar et al.
†Data from this trial cannot be summarized within this framework; however, results were statistically significant and similar in magnitude to other trials.
NNT, number needed to treat; NNH, number needed to harm; CI, confidence interval

Recommendations from Others

American Diabetes Association practice guidelines do not address neuropathy; UptoDate emphasizes prevention through glycemic control, with initial treatment using amitriptyline or nortriptyline, followed by capsaicin and anticonvulsants.5

CLINICAL COMMENTARY:

Anticonvulsants and antidepressants effective at reducing perception of pain
Charissa Fotinos, MD
Seattle–King County Public Health, Seattle, Wash

The management of patients with chronic pain requires a combination of artistry and skill. As each individual’s perceptions, expectations and response to therapy differ, dynamic treatment approaches are required. The relative dearth of evidence supporting effective treatments for chronic pain compounds the problem. This evidence review helps to lessen some of the guesswork for patients with diabetic neuropathy. Anticonvulsants and antidepressants are impressively effective at reducing patients’ perceptions of pain at a favorable benefit to significant harm ratio, NNT of 2–4 vs. NNH of 18. Several things however, aren’t clear from the literature: as these were all placebo comparisons, which drug is more effective? As well, were reductions in functional limitation and disability measures or improvements in quality of life scores demonstrated? Will other newer agents prove to be superior? Despite these unanswered questions, for patients with diabetic neuropathy good evidence now supports what has likely been many clinicians’ preference for the treatment of most chronic pain conditions; any alternative to narcotics.