Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy.
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 L Cavalleri, John Craig, Norman Delanty, Michael R Johnson, Bobby P C 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, EpiPGX Consortium
Author Information
Katri Silvennoinen: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK. ORCID
Nikola de Lange: Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux Luxembourg.
Sara Zagaglia: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK.
Simona Balestrini: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK.
Ganna Androsova: Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux Luxembourg.
Merel Wassenaar: Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands.
Pauls Auce: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine University of Liverpool Liverpool UK.
Andreja Avbersek: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK.
Felicitas Becker: Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany.
Bianca Berghuis: Stichting Epilepsie Instellingen Nederland (SEIN) Heemstede The Netherlands.
Ellen Campbell: Belfast Health and Social Care Trust Belfast UK.
Antonietta Coppola: Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa Genoa Italy.
Ben Francis: Department of Biostatistics University of Liverpool Liverpool UK.
Stefan Wolking: Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany.
Gianpiero L Cavalleri: Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland. ORCID
John Craig: Belfast Health and Social Care Trust Belfast UK.
Norman Delanty: Molecular and Cellular Therapeutics Royal College of Surgeons in Ireland Dublin Ireland. ORCID
Michael R Johnson: Faculty of Medicine, Division of Brain Sciences Imperial College London UK.
Bobby P C Koeleman: Department of Genetics University Medical Center Utrecht Utrecht The Netherlands.
Wolfram S Kunz: Department of Epileptology University of Bonn Bonn Germany.
Holger Lerche: Hertie Institute for Clinical Brain Research University of Tübingen Tübingen Germany.
Anthony G Marson: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine University of Liverpool Liverpool UK.
Terence J O'Brien: Departments of Neuroscience and Neurology, Central Clinical School Monash University, The Alfred Hospital Melbourne Vic. Australia.
Josemir W Sander: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK.
Graeme J Sills: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine University of Liverpool Liverpool UK.
Pasquale Striano: Pediatric Neurology and Muscular Diseases Unit IRCCS Istituto G. Gaslini Genova Italy. ORCID
Federico Zara: Laboratory of Neurogenetics and Neuroscience IRCCS Istituto G. Gaslini Genova Italy.
Job van der Palen: University of Twente Enschede The Netherlands.
Roland Krause: Luxembourg Centre for Systems Biomedicine University of Luxembourg Belvaux Luxembourg. ORCID
Chantal Depondt: Department of Neurology Hôpital Erasme, Université Libre de Bruxelles Brussels Belgium. ORCID
Sanjay M Sisodiya: Department of Clinical and Experimental Epilepsy UCL Queen Square Institute of Neurology London UK. ORCID
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], < 0.001) and female sex (1.41 [1.07-1.85], = 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], < 0.001 and 1.93 [1.31-2.86], < 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%, = 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.
