Summary of findings 3.
Summary of findings ‐ Time to withdrawal of allocated treatment for individuals with generalised seizures
| Antiepileptic drug monotherapy for epilepsy: time to withdrawal of allocated treatment for individuals with generalised seizures | ||||||
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Patient or population: adults and children with generalised seizures* Settings: outpatients Intervention: carbamazepine, phenobarbitone, phenytoin, lamotrigine, oxcarbazepine, topiramate, gabapentin, levetiracetam and zonisamide. Comparison: sodium valproate | ||||||
|
Intervention (experimental treatment)a,b |
Comparison (reference treatment) |
No of participants (studies) with direct evidence |
Relative effect HR (95% CI) Direct evidence (pairwise meta‐analysis)c Heterogeneity: I2 |
Relative effect HR (95% CI) Direct plus indirect evidence (network meta‐analysis)c |
Proportion of direct evidence (%)d | Quality of the evidence (GRADE) |
| Carbamazepine | Sodium Valproate | 405 (4 studies) |
0.79 (0.45 to 1.37) I2 = 6.6% |
1.42 (1.09 to 1.85) | 27.3% | ⊕⊕⊕⊕ highe,f |
| Phenobarbitone | Sodium Valproate | 94 (2 studies) |
1.79 (0.65 to 5.00) I2 = 0% |
2.09 (1.17 to 3.75) | 19.4% | ⊕⊕⊕⊝ moderatee,f,g |
| Phenytoin | Sodium Valproate | 326 (3 studies) |
1.52 (0.68 to 3.33) I2 = 22.6% |
1.30 (0.79 to 2.15) | 19.3% | ⊕⊕⊕⊕ highe,f |
| Lamotrigine | Sodium Valproate | 387 (3 studies) |
0.46 (0.22 to 0.97) I2 = 0% |
0.90 (0.60 to 1.35) | 14.8% | ⊕⊕⊕⊕ highe,f |
| Oxcarbazepine | Sodium Valproate | No direct evidence | No direct evidence I2: NA |
1.42 (0.29 to 6.92) | 0% | ⊕⊕⊕⊝ moderatee,f,g |
| Topiramate | Sodium Valproate | 443 (2 studies) |
1.04 (0.52 to 2.07) I2 = 48.5% |
1.76 (1.22 to 2.53) | 22.4% | ⊕⊕⊕⊝ moderatee,f,h |
| Gabapentin | Sodium Valproate | No direct evidence | No direct evidence I2: NA |
1.28 (0.16 to 10.5) | 0% | ⊕⊕⊕⊝ moderatee,f,g |
| Levetiracetam | Sodium Valproate | 512 (1 study) |
0.68 (0.30 to 1.59) I2: NA) |
1.05 (0.58 to 1.90) | 18.6% | ⊕⊕⊕⊕ highe,f |
| Abbreviations: CI: confidence interval; HR: hazard Ratio; NA: not applicable | ||||||
| GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: we are very uncertain about the estimate. | ||||||
*Generalised tonic‐clonic seizures with or without other seizure types is shortened to 'Generalised seizures' for brevity
aOrder of drugs in the table: most commonly used drug first (carbamazepine), then drugs are ordered approximately by the date they were licenced as a monotherapy treatment (oldest first). bHR < 1 indicates an advantage to the experimental treatment. cHRs and 95% CIs are calculated from fixed‐effect analyses (pairwise and network meta‐analysis). dProportion of the estimate contributed by direct evidence. eSeveral trials contributing direct evidence or contributing to the network meta‐analysis were at high risk of bias for at least one domain (see Risk of bias in included studies); we performed numerous sensitivity analyses in the case of particular sources of bias or inconsistencies within individual participant data provided to us (see Sensitivity analysis for full details). Results of sensitivity analyses showed similar numerical results and no changes to conclusions, therefore we judged that any risks of bias within the trials included in these analyses have not influenced the overall results (no downgrade of quality of evidence). fNo indication of inconsistency between direct evidence and network meta‐analysis results (no downgrade of quality of evidence). gWide or very wide confidence intervals on the network meta‐analysis estimate (downgraded once for imprecision). hConfidence intervals of estimate from direct evidence and from network meta‐analysis do not overlap indicating potential inconsistency (quality of the evidence downgraded once due this potential inconsistency, see Effects of interventions for further discussion).