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Meta-Analysis
. 2017 May 18;5(5):CD010483.
doi: 10.1002/14651858.CD010483.pub4.

Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy

Francesco Brigo  1 , Stanley C Igwe  2 , Nicola Luigi Bragazzi  3
Affiliations
Meta-Analysis

Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy

Francesco Brigo et al. Cochrane Database Syst Rev. .

Abstract

Background: This is an updated version of the original Cochrane review published in 2015, Issue 10.Severe myoclonic epilepsy in infants (SMEI), also known as Dravet syndrome, is a rare, refractory form of epilepsy, for which stiripentol (STP) has been recently licensed as add-on therapy.

Objectives: To evaluate the efficacy and tolerability of STP and other antiepileptic drug treatments (including ketogenic diet) for patients with SMEI.

Search methods: For the latest update we searched the Cochrane Epilepsy Group Specialized Register (20 December 2016), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 20 December 2016), MEDLINE (Ovid, 1946 to 20 December 2016) and ClinicalTrials.gov (20 December 2016). Previously we searched the World Health Organization (WHO) International Clinical Trials Registry Platform ICTRP, but this was not usable at the time of this update. We also searched the bibliographies of identified studies for additional references. We handsearched selected journals and conference proceedings and imposed no language restrictions.

Selection criteria: Randomised controlled trials (RCTs) or quasi-randomised controlled trials; double- or single-blinded or unblinded trials; and parallel-group studies. Administration of at least one antiepileptic drug therapy given singly (monotherapy) or in combination (add-on therapy) compared with add-on placebo or no add-on treatment.

Data collection and analysis: Review authors independently selected trials for inclusion according to predefined criteria, extracted relevant data and evaluated the methodological quality of trials. We assessed the following outcomes: 50% or greater seizure reduction, seizure freedom, adverse effects, proportion of dropouts and quality of life. We assessed outcomes by using a Mantel-Haenszel meta-analysis to calculate risk ratios (RRs) with 95% confidence intervals (95% CIs).

Main results: Since the last version of this review no new studies have been found. Specifically, we found no RCTs assessing drugs other than STP. The review includes two RCTs evaluating use of STP (total of 64 children). Both studies were generally at unclear risk of bias. A significantly higher proportion of participants had 50% or greater reduction in seizure frequency in the STP group compared with the placebo group (22/33 versus 2/31; RR 10.40, 95% CI 2.64 to 40.87). A significantly higher proportion of participants achieved seizure freedom in the STP group compared with the placebo group (12/33 versus 1/31; RR 7.93, 95% CI 1.52 to 41.21). Investigators found no significant differences in proportions of dropouts from the STP group compared with the placebo group (2/33 versus 8/31; RR 0.24, 95% CI 0.06 to 1.03). Only one study explicitly reported the occurrence of side effects, noting that higher proportions of participants in the STP group experienced side effects than in the placebo group (100% versus 25%; RR 3.73, 95% CI 1.81 to 7.67). We rated the quality of the evidence as low to moderate according to GRADE criteria, as most information is from studies judged to be at an unclear risk of bias.

Authors' conclusions: Data derived from two small RCTs indicate that STP is significantly better than placebo with regards to 50% or greater reduction in seizure frequency and seizure freedom. Adverse effects occurred more frequently with STP. Additional adequately powered studies with long-term follow-up should be conducted to unequivocally establish the long-term efficacy and tolerability of STP in the treatment of patients with SMEI.

PubMed Disclaimer

Conflict of interest statement

FB: Francesco Brigo has received speaker's honoraria and travel support from Eisai and UCB Pharma. He has also acted as a consultant for EISAI.

SI: none known.

NB: none known.

Clarification statement added from the Co‐ordinating Editor on 22 June 2020: This review was found by the Cochrane Funding Arbiters, post‐publication, to be noncompliant with the Cochrane conflict of interest policy, which includes the relevant parts of the Cochrane Commercial Sponsorship Policy. It will be updated within twelve 12 months. The update will have a majority of authors and lead author free of conflicts."

Figures

1
1
Study flow diagram. This diagram refers only to results of the updated searches for the present version of the review.
2
2
'Risk of bias' graph: review authors' judgements about all risk of bias items presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: STP versus placebo, Outcome 1: ≥ 50% reduction in seizure frequency
1.2
1.2. Analysis
Comparison 1: STP versus placebo, Outcome 2: Seizure freedom
1.3
1.3. Analysis
Comparison 1: STP versus placebo, Outcome 3: Proportion of dropouts
1.4
1.4. Analysis
Comparison 1: STP versus placebo, Outcome 4: ≥ 50% reduction in seizure frequency, worst‐case analysis
1.5
1.5. Analysis
Comparison 1: STP versus placebo, Outcome 5: ≥ 50% reduction in seizure frequency, best‐case analysis
1.6
1.6. Analysis
Comparison 1: STP versus placebo, Outcome 6: Seizure freedom, worst‐case analysis
1.7
1.7. Analysis
Comparison 1: STP versus placebo, Outcome 7: Seizure freedom, best‐case analysis
1.8
1.8. Analysis
Comparison 1: STP versus placebo, Outcome 8: Participants with adverse effects (any type)
1.9
1.9. Analysis
Comparison 1: STP versus placebo, Outcome 9: Drowsiness
1.10
1.10. Analysis
Comparison 1: STP versus placebo, Outcome 10: Loss of appetite
1.11
1.11. Analysis
Comparison 1: STP versus placebo, Outcome 11: Loss of weight
1.12
1.12. Analysis
Comparison 1: STP versus placebo, Outcome 12: Weight gain
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Chiron 2000 {published data only}
    1. Chiron C, Marchand MC, Tran A, Rey E, d'Athis P, Vincent J, et al. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO Study Group. Lancet 2000;356(9242):1638-42. - PubMed
Guerrini 2002 {published data only}
    1. Guerrini R, Tonnelier S, d´Athis P, Rey E, Vincent J, Pons G. Stiripentol in severe myoclonic epilepsy in infancy (SMEI): a placebo-controlled Italian trial. Epilepsia 2002;43(Suppl 8):155.

Additional references

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Dravet 2005
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Fisher 2009
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Fujiwara 2003
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Giraud 2006
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Perez 1999
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References to other published versions of this review

Brigo 2013 A
    1. Brigo F, Storti M, Del Felice A. Antiepileptic drugs for the treatment of severe myoclonic epilepsy in infancy. Cochrane Database of Systematic Reviews 2013, Issue 4. [DOI: 10.1002/14651858.CD010483] - DOI - PubMed
Brigo 2013 B
    1. Brigo F, Storti M. Antiepileptic drugs for the treatment of severe myoclonic epilepsy in infancy. Cochrane Database of Systematic Reviews 2013, Issue 11. [DOI: 10.1002/14651858.CD010483.pub2] - DOI - PubMed
Brigo 2015
    1. Brigo F, Igwe SC. Antiepileptic drugs for the treatment of infants with severe myoclonic epilepsy. Cochrane Database of Systematic Reviews 2015, Issue 10. [DOI: 10.1002/14651858.CD010483.pub3] - DOI - PubMed

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