Topiramate vs placebo in painful diabetic neuropathy: analgesic and metabolic effects.
BACKGROUND
Using identical methods, three simultaneous placebo-controlled trials of topiramate for painful diabetic neuropathy (PDN) did not reach significance. This independent yet concurrent placebo-controlled trial used different methods to assess topiramate efficacy and tolerability in PDN.


METHODS
This 12-week, multicenter, randomized, double-blind trial included 323 subjects with PDN and pain visual analog (PVA) score of at least 40 on a scale from 0 (no pain) to 100 (worst possible pain). Topiramate (n = 214) or placebo (n = 109) was titrated to 400 mg daily or maximum tolerated dose. Short-acting rescue analgesics were permitted only during the first 6 weeks.


RESULTS
Baseline characteristics were comparable between groups except for mean body weight (topiramate, 101.4 kg; placebo, 95.7 kg; p = 0.028). Twelve weeks of topiramate treatment reduced PVA scale score (from 68.0 to 46.2 mm) more effectively than placebo (from 69.1 to 54.0 mm; p = 0.038). Fifty percent of topiramate-treated subjects and 34% of placebo-treated subjects responded to treatment, defined as >30% reduction in PVA scale score (p = 0.004). Topiramate monotherapy also reduced worst pain intensity (p = 0.003 vs placebo) and sleep disruption (p = 0.020 vs placebo). Diarrhea, loss of appetite, and somnolence were the most commonly reported adverse events in the topiramate group. Topiramate reduced body weight (-2.6 vs +0.2 kg for placebo; p < 0.001) without disrupting glycemic control.


CONCLUSIONS
Topiramate monotherapy reduced pain and body weight more effectively than placebo in patients with painful diabetic neuropathy.
Raskin
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Clifton and Betsy Robinson Chair in Biomedical Research, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8858, USA. Philip.Raskin@UTSouthwestern.edu
Donofrio
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Rosenthal
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Hewitt
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Jordan
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Xiang
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Vinik
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001066:Appetite / Q000187:drug effects; D001067:Appetite Depressants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007866:Leg / Q000294:innervation; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D010352:Patient Dropouts; D020919:Sleep Disorders, Intrinsic / Q000188:drug therapy / Q000209:etiology; D000077236:Topiramate; D016896:Treatment Outcome
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001067:Appetite Depressants; D000077236:Topiramate; D005632:Fructose