Summary of findings 1. Ethosuximide compared to valproate for absence seizures in children and adolescents.
| Ethosuximide compared to valproate for absence seizures in children and adolescents | ||||||
| Patient or population: absence seizures in children and adolescents Setting: outpatients Intervention: ethosuximide Comparison: valproate | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with valproate | Risk with ethosuximide | |||||
| Seizure freedom at 12 months | Study population | ‐ | 365 (4 RCTs) | ⊕⊕⊕⊝ MODERATE 1 | None of the included trials found a difference for this outcome. Length of follow‐up in included studies: from 6 weeks to 4 years. |
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| see comment | see comment | |||||
| 80% or greater reduction in seizure frequency | Study population | RR 0.70 (0.19 to 2.59) | 29 (1 RCT)a | ⊕⊝⊝⊝ VERY LOW 2,3 | No difference was found, but the confidence interval is wide and equivalence cannot be inferred. Length of follow‐up: 6 weeks. |
|
| 286 per 1,000 | 200 per 1,000 (54 to 740) | |||||
| 50% or greater reduction in seizure frequency | Study population | ‐ | 49 (2 RCTs) | ⊕⊕⊝⊝ LOW 4,5 | No difference was found, but the confidence interval is wide and equivalence cannot be inferred. Length of follow‐up in included studies: from 1 to 4 years. |
|
| see comment | see comment | |||||
| Normalisation of the EEG ‐ not reported | ‐ | ‐ | ‐ | ‐ | ‐ | |
| Adverse effects (Table 2; Table 3) Ethosuximide treatment was mostly associated with nausea, vomiting, and behavioural/psychiatric changes. The most common adverse effects of treatment with valproate were fatigue, nausea, vomiting, increased appetite with weight gain, behavioural/psychiatric changes (decreased concentration, personality change, hyperactivity, attention problems, hostility), and thrombocytopenia | ||||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; 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. | ||||||
1 Most information is from studies at low or unclear risk of bias; plausible bias is likely to seriously alter the results.
2 Information is from a study with unclear and high risk of bias; plausible bias is likely to seriously alter the results.
3 Small number of patients included in this study (29) (see also footnote below).
4 Information is from two small studies with unclear or high risk of bias; plausible bias is likely to seriously alter the results.
5 Information is from two studies with small number of patients included.
aIn this study, one patient in the ethosuximide group was subsequently treated with valproate, but failed to respond to either single drug and did not improve when both drugs were used in combination. The outcomes of this patient on combined treatment were therefore counted twice ("no remission"), since the patient received both drugs.