Topiramate in painful diabetic polyneuropathy: findings from three double-blind placebo-controlled trials.
OBJECTIVE
To evaluate the efficacy and tolerability of topiramate in patients with painful diabetic polyneuropathy.


METHODS
Patients with moderate to extreme pain (0-4 Categorical Pain Scale score > or = 2) were randomized to placebo or topiramate (100, 200, or 400 mg/day) in three similar double-blind trials. The primary efficacy analysis was pain reduction from final visit to baseline in the 100-mm Visual Analog Scale (VAS) for the intent-to-treat populations.


RESULTS
After 18-22 weeks of double-blind treatment, pain reductions were numerically greater with topiramate in two studies but differences between topiramate and placebo in VAS scores or in the secondary efficacy endpoints did not reach statistical significance in any of the three studies. Across all studies, 24% of topiramate-treated patients and 8% of placebo-treated patients discontinued due to adverse events; groups did not differ in the occurrence of serious adverse events.


CONCLUSIONS
These studies did not find topiramate to be significantly more effective than placebo in reducing pain scores in patients with painful diabetic polyneuropathy. Several design features may have precluded the studies from having sufficient sensitivity to differentiate effective and ineffective treatments. The study design and results are instructive for other investigators designing future clinical studies in neuropathic pain.
Thienel
U
U
Therakos, Exton, PA, USA.
Neto
W
W
Schwabe
S K
SK
Vijapurkar
U
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003929:Diabetic Neuropathies / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010147:Pain Measurement; D000077236:Topiramate
D018696:Neuroprotective Agents; D000077236:Topiramate; D005632:Fructose