Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Nov 24;11(11):CD010008.
doi: 10.1002/14651858.CD010008.pub5.

Topiramate for juvenile myoclonic epilepsy

Jia Liu  1 , Yao-Jun Tai  2 , Lu-Ning Wang  3
Affiliations

Topiramate for juvenile myoclonic epilepsy

Jia Liu et al. Cochrane Database Syst Rev. .

Abstract

Background: Topiramate is a newer broad-spectrum antiepileptic drug (AED). Some studies have shown the benefits of topiramate in the treatment of juvenile myoclonic epilepsy (JME). However, there are no current systematic reviews to determine the efficacy and tolerability of topiramate in people with JME. This is an update of a Cochrane Review first published in 2015, and last updated in 2019.

Objectives: To evaluate the efficacy and tolerability of topiramate in the treatment of JME.

Search methods: For the latest update, we searched the Cochrane Register of Studies (CRS Web) on 26 August 2021, and MEDLINE (Ovid 1946 to 26 August 2021). CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups, including Cochrane Epilepsy.

Selection criteria: We included randomized controlled trials (RCTs) investigating topiramate versus placebo or other AED treatment for people with JME, with the outcomes of proportion of responders and proportion of participants experiencing adverse events (AEs).

Data collection and analysis: Two review authors independently screened the titles and abstracts of identified records, selected studies for inclusion, extracted data, cross-checked the data for accuracy and assessed the methodological quality of the studies.

Main results: We included three studies with a total of 83 participants. For efficacy, a greater proportion of participants in the topiramate group had a 50% or greater reduction in primarily generalized tonic-clonic seizures (PGTCS), compared with participants in the placebo group (RR 4.00, 95% CI 1.08 to 14.75; 1 study, 22 participants; very low-certainty evidence). There were no significant differences between topiramate and valproate for participants responding with a 50% or greater reduction in myoclonic seizures (RR 0.88, 95% CI 0.67 to 1.15; one study, 23 participants; very-low certainty evidence) or in PGTCS (RR 1.22, 95% CI 0.68 to 2.21; one study, 16 participants, very-low certainty evidence), or participants becoming seizure-free (RR 1.13, 95% CI 0.61 to 2.11; one study, 27 participants; very-low certainty evidence). Concerning tolerability, we ranked AEs associated with topiramate as moderate to severe, while we ranked 59% of AEs linked to valproate as severe complaints (2 studies, 61 participants; very low-certainty evidence). Moreover, systemic toxicity scores were higher in the valproate group than the topiramate group. Overall we judged all three studies to be at high risk of attrition bias and at unclear risk of reporting bias. We judged the studies to be at low to unclear risk of bias for the remaining domains (selection bias, performance bias, detection bias and other bias). We judged the overall certainty of the evidence for the outcomes as very low using the GRADE approach.

Authors' conclusions: We have found no new studies since the last version of this review was published in 2019. This review does not provide sufficient evidence to support topiramate for the treatment of people with JME. Based on the current limited available data, topiramate seems to be better tolerated than valproate, but has no clear benefits over valproate in terms of efficacy. Well-designed, double-blind RCTs with large samples are required to test the efficacy and tolerability of topiramate in people with JME.

PubMed Disclaimer

Conflict of interest statement

Jia Liu: none known

Yao‐Jun Tai: none known

Lu‐Ning Wang: none known

Figures

1
1
Study flow diagram
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Topiramate versus placebo, Outcome 1: Proportion of responders (at least 50% seizure frequency reduction in PGTCS)
1.2
1.2. Analysis
Comparison 1: Topiramate versus placebo, Outcome 2: Nausea
1.3
1.3. Analysis
Comparison 1: Topiramate versus placebo, Outcome 3: Upper respiratory tract infection
1.4
1.4. Analysis
Comparison 1: Topiramate versus placebo, Outcome 4: Abnormal vision
1.5
1.5. Analysis
Comparison 1: Topiramate versus placebo, Outcome 5: Diarrhea
2.1
2.1. Analysis
Comparison 2: Topiramate versus valproate, Outcome 1: Proportion of responders (at least 50% seizure frequency reduction in myoclonic seizures)
2.2
2.2. Analysis
Comparison 2: Topiramate versus valproate, Outcome 2: Proportion of responders (at least 50% seizure frequency reduction in PGTCS)
2.3
2.3. Analysis
Comparison 2: Topiramate versus valproate, Outcome 3: Number of participants who were seizure‐free
2.4
2.4. Analysis
Comparison 2: Topiramate versus valproate, Outcome 4: Paresthesia
2.5
2.5. Analysis
Comparison 2: Topiramate versus valproate, Outcome 5: Weight gain
2.6
2.6. Analysis
Comparison 2: Topiramate versus valproate, Outcome 6: Tremor
2.7
2.7. Analysis
Comparison 2: Topiramate versus valproate, Outcome 7: Headache
2.8
2.8. Analysis
Comparison 2: Topiramate versus valproate, Outcome 8: Concentration difficulty
2.9
2.9. Analysis
Comparison 2: Topiramate versus valproate, Outcome 9: Fatigue
2.10
2.10. Analysis
Comparison 2: Topiramate versus valproate, Outcome 10: Alopecia
2.11
2.11. Analysis
Comparison 2: Topiramate versus valproate, Outcome 11: Dizziness
2.12
2.12. Analysis
Comparison 2: Topiramate versus valproate, Outcome 12: Weight loss
2.13
2.13. Analysis
Comparison 2: Topiramate versus valproate, Outcome 13: Psychomotor slowing
2.14
2.14. Analysis
Comparison 2: Topiramate versus valproate, Outcome 14: Somnolence
2.15
2.15. Analysis
Comparison 2: Topiramate versus valproate, Outcome 15: Nausea
2.16
2.16. Analysis
Comparison 2: Topiramate versus valproate, Outcome 16: Appetite increase
2.17
2.17. Analysis
Comparison 2: Topiramate versus valproate, Outcome 17: Insomnia
2.18
2.18. Analysis
Comparison 2: Topiramate versus valproate, Outcome 18: Abnormal vision
2.19
2.19. Analysis
Comparison 2: Topiramate versus valproate, Outcome 19: Rash
2.20
2.20. Analysis
Comparison 2: Topiramate versus valproate, Outcome 20: Anorexia
2.21
2.21. Analysis
Comparison 2: Topiramate versus valproate, Outcome 21: Hallucination
2.22
2.22. Analysis
Comparison 2: Topiramate versus valproate, Outcome 22: Diarrhea
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

Cited by

References

References to studies included in this review

Biton 2005 {published data only}
    1. Biton V, Bourgeois BF, YTC/YTCE Study Investigators. Topiramate in patients with juvenile myoclonic epilepsy. Archives of Neurology 2005;62(11):1705-8. [PMID: ] - PubMed
Levisohn 2007 {published data only}
    1. Levisohn PM, Holland KD. Topiramate or valproate in patients with juvenile myoclonic epilepsy: a randomized open-label comparison. Epilepsy & Behavior 2007;10(4):547-52. [PMID: ] - PubMed
Park 2013 {published data only}
    1. Park KM, Kim SH, Nho SK, Shin KJ, Park J, Ha SY, et al. A randomized open-label observational study to compare the efficacy and tolerability between topiramate and valproate in juvenile myoclonic epilepsy. Journal of Clinical Neuroscience 2013;20(8):1079-82. [PMID: ] - PubMed

References to studies excluded from this review

Sousa 2005 {published data only}
    1. Sousa Pda S, Araújo Filho GM, Garzon E, Sakamoto AC, Yacubian EM. Topiramate for the treatment of juvenile myoclonic epilepsy. Arquivos de Neuro-psiquiatria 2005;63(3B):733-7. [PMID: ] - PubMed

Additional references

Alfradique 2007
    1. Alfradique I, Vasconcelos MM. Juvenile myoclonic epilepsy. Arquivos de Neuro-psiquiatria 2007;65(4B):1266-71. [PMID: ] - PubMed
Biton 1999
    1. Biton V, Montouris GD, Ritter F, Riviello JJ, Reife R, Lim P, et al. A randomized, placebo-controlled study of topiramate in primary generalized tonic-clonic seizures. Neurology 1999;52(7):1330-7. [PMID: ] - PubMed
Calleja 2001
    1. Calleja S, Salas-Puig J, Ribacoba R, Lahoz CH. Evolution of juvenile myoclonic epilepsy treated from the outset with sodium valproate. Seizure 2001;10(6):424-7. [PMID: ] - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG (editors). Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Elbourne 2002
    1. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. International Journal of Epidemiology 2002;31(1):140-9. [PMID: ] - PubMed
Guberman 2002
    1. Guberman A, Neto W, Gassmann-Mayer C, EPAJ-119 Study Group. Low-dose topiramate in adults with treatment-resistant partial-onset seizures. Acta Neurologica Scandinavica 2002;106(4):183-9. [PMID: ] - PubMed
Hanaya 1998
    1. Hanaya R, Sasa M, Ujihara H, Ishihara K, Serikawa T, Iida K, et al. Suppression by topiramate of epileptiform burst discharges in hippocampal CA3 neurons of spontaneously epileptic rat in vitro. Brain Research 1998;789(2):274-82. [PMID: ] - PubMed
Higgins 2003
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327(7414):557-60. [PMID: ] - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Jallon 2005
    1. Jallon P, Latour P. Epidemiology of idiopathic generalized epilepsies. Epilepsia 2005;46(Suppl 9):10-4. [PMID: ] - PubMed
Janz 1985
    1. Janz D. Epilepsy with impulsive petit mal (juvenile myoclonic epilepsy). Acta Neurologica Scandinavica 1985;72(5):449-59. [PMID: ] - PubMed
Kirkham 2010
    1. Kirkham JJ, Dwan KM, Altman DG, Gamble C, Dodd S, Smyth R, et al. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews. BMJ 2010;340:c365. [PMID: ] - PubMed
Lefebvre 2021
    1. Lefebvre C, Glanville J, Briscoe S, Littlewood A, Marshall C, Metzendorf M-I, et al. Technical Supplement to Chapter 4: Searching for and selecting studies. In: Higgins JPT, Thomas J, Chandler J, Cumpston MS, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2021). Cochrane, 2021. Available from www.training.cochrane.org/handbook.
Montouris 2009
    1. Montouris G, Abou-Khalil B. The first line of therapy in a girl with juvenile myoclonic epilepsy: should it be valproate or a new agent? Epilepsia 2009;50(Suppl 8):16-20. [PMID: ] - PubMed
Panayiotopoulos 1991
    1. Panayiotopoulos CP, Tahan R, Obeid T. Juvenile myoclonic epilepsy: factors of error involved in the diagnosis and treatment. Epilepsia 1991;32(5):672-6. [PMID: ] - PubMed
Review Manager 2014 [Computer program]
    1. Review Manager 5 (RevMan 5). Version 5.4. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Sachdeo 1999
    1. Sachdeo RC, Glauser TA, Ritter F, Reife R, Lim P, Pledger G, Topiramate YL Study Group. A double-blind, randomized trial of topiramate in Lennox-Gastaut syndrome. Neurology 1999;52(9):1882-7. [PMID: ] - PubMed
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Guyatt GH. Chapter 11: Presenting results and ‘Summary of findings' tables. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A (editors). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Serafini 2019
    1. Serafini A, Gerard E, Genton E, Crespel A, Gelisse P. Treatment of juvenile myoclonic epilepsy in patients of child-bearing potential. CNS Drugs 2019;33(3):195-208. - PubMed
Sharpe 2008
    1. Sharpe DV, Patel AD, Abou-Khalil B, Fenichel GM. Levetiracetam monotherapy in juvenile myoclonic epilepsy. Seizure 2008;17(1):64-8. [PMID: ] - PubMed
White 2000
    1. White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism. Epilepsia 2000;41(Suppl 1):17-20. [PMID: ] - PubMed
Zona 1997
    1. Zona C, Ciotti MT, Avoli M. Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells. Neuroscience Letters 1997;231(3):123-6. [PMID: ] - PubMed

References to other published versions of this review

Liu 2012
    1. Liu J, Wang LN. Topiramate monotherapy for juvenile myoclonic epilepsy. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No: CD010008. [DOI: 10.1002/14651858.CD010008] - DOI - PubMed
Liu 2015
    1. Liu J, Wang LN, Wang YP. Topiramate monotherapy for juvenile myoclonic epilepsy. Cochrane Database of Systematic Reviews 2015, Issue 12. Art. No: CD010008. [DOI: 10.1002/14651858.CD010008.pub2] - DOI - PubMed
Liu 2017
    1. Liu J, Wang LN, Wang YP. Topiramate monotherapy for juvenile myoclonic epilepsy. Cochrane Database of Systematic Reviews 2017, Issue 4. Art. No: CD010008. [DOI: 10.1002/14651858.CD010008.pub3] - DOI - PMC - PubMed
Liu 2019
    1. Liu J, Wang LN, Wang YP. Topiramate for juvenile myoclonic epilepsy. Cochrane Database of Systematic Reviews 2019, Issue 1. Art. No: CD010008. [DOI: 10.1002/14651858.CD010008.pub4] - DOI - PMC - PubMed

Publication types

MeSH terms

LinkOut - more resources