Royal College of Surgeons in Ireland
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Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

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posted on 2021-04-09, 15:58 authored by Katri Silvennoinen, Nikola de Lange, Sara Zagaglia, Simona Balestrini, Ganna Androsova, Merel Wassenaar, Pauls Auce, Andreja Avbersek, Felicitas Becker, Bianca Berghuis, Ellen Campbell, Antonietta Coppola, Ben Francis, Stefan Wolking, Gianpiero CavalleriGianpiero Cavalleri, John Craig, Norman DelantyNorman Delanty, Michael R Johnson, Bobby PC Koeleman, Wolfram S Kunz, Holger Lerche, Anthony G Marson, Terence J O’Brien, Josemir W Sander, Graeme J Sills, Pasquale Striano, Federico Zara, Job van der Palen, Roland Krause, Chantal Depondt, Sanjay M Sisodiya, the EpiPGX Consortium

Objective: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME).

Methods: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females.

Results: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13], P < 0.001) and female sex (1.41 [1.07-1.85], P = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15-5.02], P < 0.001 and 1.93 [1.31-2.86], P < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%, P = 0.001).

Significance: In people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments.


NIHR Health Services and Delivery Research Programme

Royal Melbourne Hospital Foundation

Epilepsy Society

Muir Maxwell Trust

EC grant, Grant/ Award Number: 279062

Wellcome Trust

BioCog (EU-funded FP7 research program)



The original article is available at

Published Citation

Silvennoinen K, de Lange N, Zagaglia S, Balestrini S, Androsova G, Wassenaar M, Auce P, Avbersek A, Becker F, Berghuis B, Campbell E, Coppola A, Francis B, Wolking S, Cavalleri GL, Craig J, Delanty N, Johnson MR, Koeleman BPC, Kunz WS, Lerche H, Marson AG, O'Brien TJ, Sander JW, Sills GJ, Striano P, Zara F, van der Palen J, Krause R, Depondt C, Sisodiya SM; EpiPGX Consortium. Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy. Epilepsia Open. 2019;4(3):420-430.

Publication Date

26 June 2019

PubMed ID



  • Beaumont Hospital
  • School of Pharmacy and Biomolecular Sciences

Research Area

  • Neurological and Psychiatric Disorders




  • Published Version (Version of Record)