Table 15.
Pairwise and network meta‐analysis results ‐ Time to first seizure for individuals with generalised seizures
| Comparisiona | Direct evidence (pairwise meta‐analysis) | Direct plus indirect evidence (network meta‐analysis) | ||||
| Number of studies | Number of participants | HR (95% CI)2,3 | I² statistic4 | Direct evidence(%)5 | HR (95% CI)2,3 | |
| CBZ vs PHB | 5 | 237 | 0.55 (0.33 to 0.92) | 50.4% | 35.5% | 1.10 (0.80 to 1.51) |
| CBZ vs PHT | 3 | 150 | 0.88 (0.51 to 1.54) | 0% | 26.6% | 0.76 (0.59 to 0.98) |
| CBZ vs VPS | 4 | 411 | 1.37 (0.98 to 1.92) | 84.1% | 10.4% | 0.88 (0.76 to 1.03) |
| CBZ vs LTG | 7 | 302 | 1.49 (0.94 to 2.35) | 0% | 0.3% | 0.98 (0.70 to 1.37) |
| CBZ vs OXC | 1 | 9 | 1.55 (0.38 to 6.31) | NA | 9% | 1.09 (0.36 to 3.36) |
| CBZ vs TPM | 2 | 101 | 1.19 (0.56 to 2.50) | 62% | 9% | 1.15 (0.89 to 1.48) |
| CBZ vs GBP | 1 | 6 | 2.83 (0.31 to 25.5) | NA | 10.7% | 0.79 (0.10 to 6.08) |
| CBZ vs LEV | 2 | 251 | 1.04 (0.65 to 1.64) | 0% | 44.9% | 1.19 (0.78 to 1.83) |
| PHB vs PHT | 4 | 161 | 1.41 (0.76 to 2.62) | 46.9% | 20.3% | 0.69 (0.48 to 1.00) |
| PHB vs VPS | 2 | 98 | 1.87 (0.87 to 4.00) | 69.8% | 6.5% | 0.80 (0.57 to 1.12) |
| PHB vs LTG | No direct evidence | 0% | 0.89 (0.56 to 1.42) | |||
| PHB vs OXC | No direct evidence | 0% | 1.00 (0.31 to 3.20) | |||
| PHB vs TPM | No direct evidence | 0% | 1.05 (0.70 to 1.56) | |||
| PHB vs GBP | No direct evidence | 0% | 0.72 (0.09 to 5.68) | |||
| PHB vs LEV | No direct evidence | 0% | 1.09 (0.64 to 1.85) | |||
| PHT vs VPS | 4 | 394 | 1.11 (0.71 to 1.74) | 0% | 36.4% | 1.16 (0.88 to 1.53) |
| PHT vs LTG | 1 | 91 | 1.00 (0.40 to 2.46) | NA | 16.2% | 1.29 (0.85 to 1.97) |
| PHT vs OXC | 2 | 154 | 0.60 (0.33 to 1.10) | 49.7% | 25.2% | 1.44 (0.46 to 4.56) |
| PHT vs TPM | 1 | 150 | 0.63 (0.18 to 2.26) | NA | 9.8% | 1.51 (1.06 to 2.15) |
| PHT vs GBP | No direct evidence | 0% | 1.05 (0.13 to 8.14) | |||
| PHT vs LEV | No direct evidence | 0% | 1.57 (0.96 to 2.58) | |||
| VPS vs LTG | 3 | 377 | 0.64 (0.37 to 1.11) | 23.2% | 31.3% | 1.11 (0.77 to 1.60) |
| VPS vs OXC | No direct evidence | 0% | 1.24 (0.40 to 3.84) | |||
| VPS vs TPM* | 2 | 441 | 0.42 (0.23 to 0.80) | 46.4% | 21% | 1.30 (1.01 to 1.68) |
| VPS vs GBP | No direct evidence | 0% | 0.90 (0.12 to 6.92) | |||
| VPS vs LEV | 1 | 512 | 0.82 (0.48 to 1.40) | NA | 34% | 1.35 (0.86 to 2.13) |
| LTG vs OXC | 1 | 10 | 0.94 (0.25 to 3.57) | NA | 12.2% | 1.12 (0.36 to 3.48) |
| LTG vs TPM | 1 | 14 | 0.61 (0.28 to 1.30) | NA | 13.1% | 1.17 (0.78 to 1.77) |
| LTG vs GBP | 1 | 7 | 1.72 (0.20 to 14.9) | NA | 11.9% | 0.81 (0.11 to 6.25) |
| LTG vs LEV | No direct evidence | 0% | 1.22 (0.71 to 2.10) | |||
| OXC vs TPM | 1 | 14 | 1.90 (0.50 to 7.19) | NA | 13.6% | 1.05 (0.34 to 3.24) |
| OXC vs GBP | 1 | 7 | 1.83 (0.20 to 16.5) | NA | 13.3% | 0.73 (0.08 to 6.49) |
| OXC vs LEV | No direct evidence | 0% | 1.09 (0.33 to 3.62) | |||
| TPM vs GBP | 1 | 11 | 0.96 (0.11 to 8.29) | NA | 13.2% | 0.69 (0.09 to 5.32) |
| TPM vs LEV | No direct evidence | 0% | 1.04 (0.63 to 1.71) | |||
| GBP vs LEV | No direct evidence | 0% | 1.50 (0.19 to 12.0) | |||
CBZ: carbamazepine; CI: confidence interval; GBP: gabapentin; HR: hazard ratio; LEV: levetiracetam; LTG: lamotrigine; OXC: oxcarbazepine; PHB: phenobarbitone; PHT: phenytoin; TPM: topiramate; VPS: sodium valproate; ZNS: zonisamide
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). bHRs and 95% CIs are calculated from fixed‐effect analyses (pairwise and network meta‐analysis); where substantial heterogeneity was present (I2 > 50%), random‐effects meta‐analysis was also conducted, see Effects of interventions for further details. cNote that HR < 1 indicates an advantage to the second drug in the comparison; results in highlighted in bold are statistically significant. dNA ‐ heterogeneity is not applicable as only one study contributed direct evidence. eDirect evidence (%) ‐ proportion of the estimate contributed by direct evidence.
For comparisons marked with a *, confidence intervals of direct evidence and network meta‐analysis do not overlap indicating that inconsistency may be present in the results