Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy.

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.
Competing Interests: AA is employed by UCB Pharma, Belgium as Associate Director. AC reports grants from Eisai outside the submitted work. JC reports personal fees from UCB Pharma, personal fees from Sanofi‐Synthelabo, personal fees from Glaxo Smith Kline, personal fees from Janssen‐Cilag, personal fees from Pfizer and personal fees from Eisai to undertake lectures, participate in advisory boards and to undertake research. HL has received honoraria for consulting or speaking or travel support from Bial, BioMarine, Desitin, Eisai, and UCB, and research support from Bial, all outside the submitted work. JWS has received research funding from Eisai, and UCB, personal fees from Eisai, Bial, Janssen and UCB outside the submitted work. In the past 36 months, GJS has received personal fees for consulting and/or speaking from UCB Pharma and Eisai, all outside the submitted work. CD has received honoraria and grant funding from UCB, unrelated to the current study. SMS reports representing the Association of British Neurologists and The Royal College of Physicians (London) at the MHRA Valproate Stakeholders Network, is a member of the scientific advisory board of Dravet Syndrome UK, patron of AHC UK. SMS has received honoraria or grant funding from UCB, Eisai, Vitaflo and Nutricia, all outside the submitted work. The remaining authors have no conflicts of interests. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.