Summary of findings for the main comparison. Topiramate compared to placebo for drug‐resistant focal epilepsy.
| Add‐on topiramate compared to placebo for drug‐resistant focal epilepsy | ||||||
| Patients or population: people with drug‐resistant focal epilepsy Setting: outpatients Intervention: add‐on topiramate Comparison: add‐on placebo | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI; Adverse effects: 99% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with topiramate | |||||
|
50% or greater reduction in seizure frequency (ITT analysis) Follow‐up: range 11 to 19 weeks |
Study population | RR 2.71 (2.05 to 3.59) | 1650 (12 RCTs) | ⊕⊕⊕⊕ Higha,b,c,f,h | Topiramate increases the proportion of participants attaining a 50% or greater reduction in seizure frequency. | |
| 163 per 1000 | 441 per 1000 (333 to 584) | |||||
|
Seizure freedom Follow‐up: range 11 to 19 weeks |
Study population | RR 3.67 (1.79 to 7.54) | 1177 (8 RCTs) | ⊕⊕⊕⊝ Moderatea,e,f | Topiramate likely increases the proportion of participants achieving seizure freedom. | |
| 17 per 1000 | 61 per 1000 (30 to 125) | |||||
|
Treatment withdrawal Follow‐up: range 11 to 19 weeks |
Study population | RR 2.37 (1.66 to 3.37) | 1650 (12 RCTs) | ⊕⊕⊕⊕ Higha,d,f | Topiramate increases the incidence of treatment withdrawal. | |
| 61 per 1000 | 144 per 1000 (101 to 204) | |||||
|
Adverse effects ‐ weight loss/decrease Follow‐up: range 11 to 18 weeks |
Study population | RR 3.99 (1.82 to 8.72) | 1070 (9 RCTs) | ⊕⊕⊝⊝ Lowa,c,e,f | Topiramate may produce a large increase in the proportion of participants experiencing weight loss. | |
| 20 per 1000 | 81 per 1000 (37 to 177) | |||||
|
Adverse effects ‐ paraesthesia Follow‐up: range 11 to 18 weeks |
Study population | RR 3.65 (1.58 to 8.39) | 1071 (7 RCTs) | ⊕⊕⊕⊝ Moderatea,e,f | Topiramate likely increases the proportion of participants experiencing paraesthesia. | |
| 25 per 1000 | 91 per 1000 (40 to 210) | |||||
|
Adverse effects ‐ 'thinking abnormally' Follow‐up: range 12 to 19 weeks |
Study population | RR 5.70 (2.26 to 14.38) | 640 (4 RCTs) | ⊕⊕⊕⊕ Higha,d,g | Topiramate increases the proportion of participants reporting that they are 'thinking abnormally'. | |
| 43 per 1000 | 243 per 1000 (96 to 614) | |||||
|
Adverse effects ‐ difficulty with concentration/concentration impaired/concentration‐attention difficulties Follow‐up: range 11 to 18 weeks |
Study population | RR 7.81 (2.08 to 29.29) | 702 (6 RCTs) | ⊕⊕⊕⊝ Moderatea,c,e,g | Topiramate likely increases the number of participants who experience difficulty with concentration. | |
| 11 per 1000 | 88 per 1000 (23 to 330) | |||||
| *The risk in the intervention group (and its 95% or 99% confidence interval, dependent on the outcome) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% or 99% CI, dependent on the outcome). CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
aWe did not downgrade evidence for risk of bias; we judged risk of bias across studies to be low. Ten studies did not describe the blinding of outcome assessors, one study failed to explain randomisation and allocation concealment and another did not describe any method of blinding. We, however, reasoned that the blinding of outcome assessors would minimally impact the estimated effect size due to the self‐reported nature of the review outcomes. bWe downgraded the evidence once for inconsistency: we detected significant statistical heterogeneity. cWe downgraded the evidence once for publication bias: examination of funnel plot and Egger test indicates the possibility of publication bias. dWe downgraded the evidence once for imprecision: the number of events (< 400) did not suffice optimal information size. eWe downgraded the evidence twice for imprecision: the number of events (< 100) did not suffice optimal information size. fWe upgraded the evidence once for large effect: RR > 2.00. gWe upgraded the evidence twice for large effect: RR > 5.00. hWe upgraded the evidence once for dose‐response gradient: logistic regression demonstrated a significant dose‐response relationship.