Introduction
Methods
Study design
Patients
Pivotal Topiramate Trials | |||||||||
---|---|---|---|---|---|---|---|---|---|
Silberstein 2004 [3]
|
Brandes 2004 [4]
|
Diener 2004 [5]
|
Pooled
| ||||||
Placebo | Topiramate 100 mg/d | Placebo | Topiramate 100 mg/d | Placebo | Topiramate 100 mg/d | Placebo | Topiramate 100 mg/d | P value* | |
No. of Patients (completers) | 115 (69) | 125 (83) | 114 (63) | 120 (63) | 143 (99) | 139 (94) | 372 (231) | 384 (240) | |
Age, Mean ± SD (yrs) | 40.4 ± 11.5 | 40.6 ± 11.0 | 38.3 ± 12.0 | 39.1 ± 12.6 | 40.4 ± 10.1 | 39.8 ± 10.9 | 39.8 ± 11.1 | 39.8 ± 11.5 | 0.939 |
Female, n (%) | 103 (90%) | 112 (90%) | 94 (82%) | 109 (91%) | 109 (76%) | 110 (79%) | 306 (82%) | 331 (86%) | 0.160 |
Caucasian, n (%) | 107 (93%) | 117 (94%) | 101 (89%) | 108 (90%) | 127 (89%) | 122 (88%) | 335 (90%) | 347 (90%) | 0.965 |
Outcome measures
Baseline Scores (Mean ± SD) | |||
---|---|---|---|
MSQ Domains
|
Placebo (n = 372)
|
Topiramate 100 mg/d (n = 384)
|
p value*
|
Role Restriction | 51.6 ± 16.2 | 48.1 ± 17.2 | 0.008 |
Role Prevention | 68.6 ± 18.9 | 67.0 ± 19.4 | 0.285 |
Emotional Function | 57.1 ± 22.7 | 53.7 ± 24.2 | 0.087 |
SF-36 Domains
|
Baseline Scores (Mean ± SD)
| ||
Placebo (n = 372)
|
Topiramate 100 mg/d (n = 384)
|
p-value
| |
Physical Functioning | 82.0 ± 20.1 | 82.1 ± 19.4 | 0.920 |
Bodily Pain | 51.3 ± 22.9 | 51.5 ± 22.4 | 0.969 |
Vitality | 51.3 ± 19.4 | 50.8 ± 20.8 | 0.891 |
General Health | 68.0 ± 19.5 | 68.8 ± 20.2 | 0.593 |
Role-Emotional | 69.0 ± 39.3 | 70.9 ± 37.7 | 0.486 |
Role-Physical | 44.5 ± 39.9 | 44.2 ± 40.8 | 0.959 |
Mental Health | 70.7 ± 17.7 | 71.4 ± 16.7 | 0.483 |
Social Functioning | 68.5 ± 22.3 | 70.0 ± 23.5 | 0.331 |
Physical Component Summary | 43.1 ± 8.6 | 42.9 ± 9.1 | 0.767 |
Mental Component Summary | 46.9 ± 10.6 | 47.5 ± 10.2 | 0.396 |
Statistical analysis
Results
Demographic and baseline characteristics of patients
Outcome measures
MSQ scores
SF-36 scores
SF-36 Domain | Treatment Group | Week 8 | Week 16 | Week 26 | End Point |
---|---|---|---|---|---|
Physical Functioning | Placebo | 3.2 ± 0.8 | 3.2 ± 0.9 | 5.0 ± 1.0 | 3.6 ± 0.9 |
Topiramate | 4.8 ± 0.8 | 6.4 ± 0.9 | 8.3 ± 1.0 | 5.3 ± 0.8 | |
NS | p = 0.025 | p = 0.023 | NS | ||
Bodily Pain | Placebo | 6.2 ± 1.2 | 6.7 ± 1.3 | 6.7 ± 1.4 | 4.6 ± 1.2 |
Topiramate | 12.0 ± 1.1 | 14.3 ± 1.4 | 14.5 ± 1.4 | 11.5 ± 1.2 | |
p < 0.001 | p < 0.001 | p < 0.001 | p < 0.001 | ||
Vitality | Placebo | 1.9 ± 1.0 | 3.1 ± 1.0 | 3.9 ± 1.2 | 1.8 ± 1.0 |
Topiramate | 3.8 ± 1.0 | 7.9 ± 1.1 | 10.1 ± 1.2 | 5.2 ± 1.0 | |
NS | p = 0.008 | p < 0.001 | p = 0.035 | ||
General Health | Placebo | 1.0 ± 0.7 | 0.4 ± 0.8 | 1.6 ± 0.9 | 0.8 ± 0.8 |
Topiramate | 3.4 ± 0.7 | 4.3 ± 0.9 | 4.5 ± 0.9 | 2.2 ± 0.8 | |
p = 0.009 | p < 0.001 | p = 0.027 | NS | ||
Role- Emotional | Placebo | 4.5 ± 2.0 | 4.1 ± 2.1 | 6.5 ± 2.3 | 3.0 ± 2.0 |
Topiramate | 2.2 ± 2.0 | 8.0 ± 2.2 | 9.3 ± 2.3 | 2.3 ± 2.0 | |
NS | NS | NS | NS | ||
Role- Physical | Placebo | 14.4 ± 2.2 | 15.0 ± 2.2 | 15.9 ± 2.5 | 12.0 ± 2.1 |
Topiramate | 19.3 ± 2.2 | 26.6 ± 2.4 | 24.1 ± 2.5 | 17.9 ± 2.1 | |
NS | p < 0.001 | p = 0.018 | NS | ||
Mental Health | Placebo | -0.2 ± 0.9 | 0.8 ± 0.8 | 0.6 ± 1.0 | -0.2 ± 0.9 |
Topiramate | -1.5 ± 0.9 | 2.9 ± 0.9 | 3.2 ± 1.0 | -0.5 ± 0.9 | |
NS | NS | p = 0.034 | NS | ||
Social Functioning | Placebo | 5.3 ± 1.2 | 7.8 ± 1.2 | 6.8 ± 1.3 | 4.8 ± 1.2 |
Topiramate | 4.8 ± 1.2 | 8.5 ± 1.3 | 10.8 ± 1.3 | 4.8 ± 1.2 | |
NS | NS | p = 0.010 | NS | ||
Physical Component Summary | Placebo | 2.8 ± 0.4 | 2.8 ± 0.4 | 3.2 ± 0.5 | 2.5 ± 0.4 |
Topiramate | 5.1 ± 0.4 | 5.7 ± 0.5 | 5.7 ± 0.5 | 4.7 ± 0.4 | |
p < 0.001 | p < 0.001 | p < 0.001 | p < 0.001 | ||
Mental Component Summary | Placebo | 0.3 ± 0.6 | 0.8 ± 0.5 | 0.9 ± 0.6 | 0.1 ± 0.5 |
Topiramate | -0.6 ± 0.6 | 1.5 ± 0.6 | 2.2 ± 0.6 | -0.2 ± 0.5 | |
NS | NS | p = 0.043 | NS |
Responder analysis
< 50% Responders | ≥ 50% Responders | |||
---|---|---|---|---|
MSQ Domain
|
n
|
Baseline
|
n
|
Baseline
|
Emotional Function | 455 | 55.5 | 244 | 55.2 |
Role Prevention | 454 | 68.3 | 243 | 67.0 |
Role Restriction | 455 | 50.1 | 244 | 49.4 |
SF-36 Subscale
|
n
|
Baseline
|
n
|
Baseline
|
Physical Functioning | 454 | 83.1 | 243 | 80.3 |
Bodily Pain | 453 | 51.4 | 244 | 51.6 |
Vitality | 454 | 51.7 | 243 | 50.0 |
General Health | 447 | 68.4 | 242 | 68.3 |
Role-Emotional | 453 | 71.0 | 240 | 68.2 |
Role Physical | 452 | 44.6 | 241 | 44.1 |
Mental Health | 454 | 71.3 | 243 | 70.7 |
Social Functioning | 455 | 69.8 | 244 | 68.6 |
Physical Component Score | 439 | 43.2 | 237 | 42.8 |
Mental Component Score | 439 | 47.4 | 237 | 46.9 |