Table 9.
Pairwise and network meta‐analysis results ‐ Time to withdrawal of allocated treatment 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)b,c | I² statisticd | Direct evidence (%)5 | HR (95% CI)b,c | |
| CBZ vs PHB | 3 | 156 | 1.21 (0.51 to 2.86) | 11.8% | 27.3% | 1.47 (0.83 to 2.61) |
| CBZ vs PHT | 2 | 118 | 2.68 (0.95 to 7.57) | 0% | 11.3% | 0.92 (0.59 to 1.42) |
| CBZ vs VPS | 4 | 405 | 1.26 (0.73 to 2.20) | 6.6% | 27.3% | 0.70 (0.54 to 0.92) |
| CBZ vs LTG | 7 | 302 | 1.23 (0.72 to 2.10) | 0% | 39.2% | 0.63 (0.45 to 0.89) |
| CBZ vs OXC | 1 | 9 | 0.39 (0.03 to 4.35) | NA | 3.9% | 1.00 (0.21 to 4.81) |
| CBZ vs TPM | 2 | 101 | 1.10 (0.51 to 2.36) | 0% | 23.2% | 1.24 (0.90 to 1.71) |
| CBZ vs GBP | 1 | 6 | 0.49 (0.03 to 7.90) | NA | 8.5% | 0.90 (0.11 to 7.29) |
| CBZ vs LEV | 2 | 251 | 1.22 (0.74 to 2.02) | 0% | 57% | 0.74 (0.44 to 1.23) |
| PHB vs PHT | 2 | 95 | 1.56 (0.49 to 4.99) | 0% | 16.1% | 0.62 (0.32 to 1.24) |
| PHB vs VPS | 2 | 94 | 0.56 (0.20 to 1.54) | 0% | 19.4% | 0.48 (0.27 to 0.86) |
| PHB vs LTG | No direct evidence | 0% | 0.43 (0.22 to 0.83) | |||
| PHB vs OXC | No direct evidence | 0% | 0.68 (0.13 to 3.60) | |||
| PHB vs TPM | No direct evidence | 0% | 0.84 (0.44 to 1.60) | |||
| PHB vs GBP | No direct evidence | 0% | 0.61 (0.07 to 5.34) | |||
| PHB vs LEV | No direct evidence | 0% | 0.50 (0.23 to 1.09) | |||
| PHT vs VPS | 3 | 326 | 0.66 (0.30 to 1.45) | 22.6% | 19.3% | 0.77 (0.46 to 1.27) |
| PHT vs LTG | 1 | 91 | 1.11 (0.42 to 2.94) | NA | 14.9% | 0.69 (0.39 to 1.20) |
| PHT vs OXC | 2 | 155 | 1.05 (0.44 to 2.52) | 0% | 37.9% | 1.09 (0.21 to 5.56) |
| PHT vs TPM | 1 | 150 | 1.68 (0.49 to 5.69) | NA | 11.2% | 1.35 (0.79 to 2.30) |
| PHT vs GBP | No direct evidence | 0% | 0.98 (0.12 to 8.30) | |||
| PHT vs LEV | No direct evidence | 0% | 0.80 (0.42 to 1.55) | |||
| VPS vs LTG | 3 | 387 | 0.46 (0.22 to 0.97) | 0% | 14.8% | 0.90 (0.60 to 1.35) |
| VPS vs OXC | No direct evidence | 0% | 1.42 (0.29 to 6.92) | |||
| VPS vs TPM* | 2 | 443 | 0.53 (0.27 to 1.07) | 48.5% | 22.4% | 1.76 (1.22 to 2.53) |
| VPS vs GBP | No direct evidence | 0% | 1.28 (0.16 to 10.5) | |||
| VPS vs LEV | 1 | 512 | 0.68 (0.30 to 1.59) | NA | 18.6% | 1.05 (0.58 to 1.90) |
| LTG vs OXC | 1 | 10 | 2.09 (0.34 to 12.8) | NA | 7.6% | 1.58 (0.33 to 7.67) |
| LTG vs TPM | 1 | 14 | 1.10 (0.42 to 2.89) | NA | 7.3% | 1.96 (1.25 to 3.08) |
| LTG vs GBP | 1 | 7 | 2.63 (0.27 to 25.7) | NA | 13.8% | 1.42 (0.17 to 11.6) |
| LTG vs LEV | No direct evidence | 0% | 1.17 (0.63 to 2.19) | |||
| OXC vs TPM | 1 | 14 | 1.31 (0.24 to 7.32) | NA | 9% | 1.24 (0.26 to 5.94) |
| OXC vs GBP | 1 | 7 | 1.26 (0.11 to 14.1) | NA | 12.7% | 0.90 (0.08 to 9.96) |
| OXC vs LEV | No direct evidence | 0% | 0.74 (0.14 to 3.86) | |||
| TPM vs GBP | 1 | 11 | 0.96 (0.11 to 8.67) | NA | 14.6% | 0.73 (0.09 to 5.89) |
| TPM vs LEV | No direct evidence | 0% | 0.60 (0.33 to 1.09) | |||
| GBP vs LEV | No direct evidence | 0% | 0.82 (0.10 to 7.10) | |||
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 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