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
| Drug | Number of controlled trials | NNT (95% CI) for 50% pain reduction | NNH (95% CI) | Efficacious dose | Typical cost |
|---|---|---|---|---|---|
| Antidepressants | 16 | 3.4 (2.6–4.7) | 2.7 (2.1–3.9) | ||
| Tricyclics | 8 | 3.5 (2.5–5.6) | 3.2 (2.3–5.2) | Amitryptiline 50–100 mg/d; Nortryptiline 50–75 mg/d | $12 |
| SSRIs | 3 | Not efficacious | N/A | N/A | |
| Anticonvulsants* | 3 | 2.7 (2.2–3.8) | 2.7 (2.2–3.4) | ||
| Phenytoin | 1 | Not available | 3.2 (2.1–6.3) | 300 mg/d | $18 |
| Carbamezapine | 1 | Not available | Not available | 400 mg 2x daily | $28 |
| Gabapentin | 2 | Not available | 2.6 (2.1–3.3) | 600–900 mg 3x daily | $333 |
| Valproate† | 1 | Not available | Rare | 400 mg 3x daily | $36 |
| Topical capsaicin | 4 | 4 (2.9–6.7) | Not available | 0.075% 4x daily | $39 |
| Lidocaine patch | 0 | Not available | Not available | 1 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.