Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

Silvennoinen, K. et al. (2019) Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy. Epilepsia Open, 4(3), pp. 420-430. (doi: 10.1002/epi4.12349) (PMID:31440723) (PMCID:PMC6698679)

Abstract

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 modelled 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.

• Item Type: Articles
• Additional Information: This study was supported by EC grant 279062, EpiPGX. This work was partly carried out at NIHR University College London Hospitals Biomedical Research Centre, which receives a proportion of funding from the UK Department of Health’s NIHR Biomedical Research Centres funding scheme. Additional funding was provided by the Muir Maxwell Trust and Epilepsy Society. KS is supported by a Wellcome Trust Strategic Award (WT104033AIA). SZ was supported by the Polytechnic University of Marche, Italy, with a 1-year research fellowship. GA has received funding from the framework of the EU-funded FP7 research program BioCog (Biomarker Development for Postoperative Cognitive Impairment in the Elderly). The Australian cohort was funded by a grant from the Royal Melbourne Hospital Foundation.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sills, Dr Graeme
• Authors: 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, G. L., Craig, J., Delanty, N., Johnson, M. R., Koeleman, B. P.C., Kunz, W. S., Lerche, H., Marson, A. G., O'Brien, T. J., Sander, J. W., Sills, G. J., Striano, P., Zara, F., van der Palen, J., Krause, R., Depondt, C., and Sisodiya, S. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Epilepsia Open
• Publisher: Wiley
• ISSN: 2470-9239
• ISSN (Online): 2470-9239
• Published Online: 26 June 2019
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in Epilepsia Open 4(3):420-430
• Publisher Policy: Reproduced under a Creative Commons License