Safety and effectiveness of topiramate for the management of painful diabetic peripheral neuropathy in an open-label extension study.
OBJECTIVE
The aim of this study was to further assess the long-term safety and effectiveness of open-label topiramate therapy in subjects with moderately to severely painful diabetic peripheral neuropathy (DPN).


METHODS
Adults aged 18 to 75 years received open-label topiramate (25-600 mg/d for 26 weeks) in an extension of a previously published randomized, double-blind trial comparing topiramate with placebo. Safety analyses included adverse event (AE) reports and clinical laboratory tests. Metabolic end points included body weight and glycosylated hemoglobin (HbA(1c)). Effectiveness analyses included a 100-mm pain visual analog (PVA) scale, worst and current pain severity, and sleep disruption.


RESULTS
Two hundred five subjects participated in this open-label extension study (118 formerly treated with topiramate and 87 who formerly received placebo). The groups did not differ in baseline demographics or disease characteristics. One hundred twenty-four (60.5%) subjects (68.6% of former topiramate recipients and 49.4% of former placebo recipients) completed the extension study; the most common reason for discontinuation was an AE (27.3% of subjects). AEs among subjects who received > or =1 dose of topiramate (n = 298) included upper respiratory tract infection (16.1%), anorexia (15.1%), diarrhea (12.8%), nausea (12.8%), paresthesia (10.7%), and headache (10.1%). Baseline pain scores were lower in those formerly treated with topiramate (n = 117) than in the former placebo group (n = 86) (PVA: 43.3 vs 52.5, P = 0.014; worst pain: 1.9 vs 2.5, P < 0.001; current pain: 1.6 vs 1.9, P = 0.026; sleep disruption: 3.6 vs 4.6, P = 0.021). At the final visit, PVA, current pain, and sleep disruption scores were not significantly different between the former topiramate and former placebo groups, but worst pain differed significantly (1.4 vs 1.8; P = 0.025). Mean weight loss from the start of topiramate therapy was 5.2 and 5.3 kg in the former topiramate and former placebo groups, respectively (P < 0.001 vs baseline). Mean HbA(1c) values before and after topiramate treatment were 7.7% and 7.4%, respectively, in the former topiramate group (P = 0.004 vs baseline), and 7.6% and 7.1%, respectively, in the former placebo group (P < 0.001 vs baseline).


CONCLUSIONS
Although 39.5% of subjects discontinued, most often due to AEs, the results of this 26-week, open-label extension study with topiramate (up to 600 mg/d) in subjects with moderately to severely painful DPN suggest that pain relief was effective and durable.
Donofrio
Peter D
PD
Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC 21757, USA. donofrio@wfubmc.edu
Raskin
Philip
P
Rosenthal
Norman R
NR
Hewitt
David J
DJ
Jordan
Donna M
DM
Xiang
Jim
J
Vinik
Aaron I
AI
D000293:Adolescent; D000328:Adult; D000368:Aged; D000855:Anorexia / Q000209:etiology; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy*; D003967:Diarrhea / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D012141:Respiratory Tract Infections / Q000209:etiology; D012892:Sleep Deprivation / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose