Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

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 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.

Trait impulsivity in Juvenile Myoclonic Epilepsy

“…The extent to which impulsivity could be reduced by improved seizure control remains an open question. JME is usually managed by AEDs with broad efficacy for generalized seizure types, 21 but it is possible that complementing these with an absence seizure‐specific AED (e.g. ethosuximide) may reduce impulsivity.…”

“…Finally, there is suggestion of increased impulsivity with topiramate use. However, exposure to topiramate, which is a second or third‐line AED for JME, 21 may be a proxy for poor seizure control or drug‐resistance, rather than representing a sign of chronic topiramate neurotoxicity.…”

“…The characterization of these discrete dimensions of impulsivity (response, choice and trait) is necessary, as they each contribute to distinct psychiatric phenotypes 16,17 . Furthermore, the clinical utility of antiepileptic drugs (AEDs), such as levetiracetam, in JME is limited by psychiatric adverse effects, which highly impulsive individuals or those with comorbid psychiatric disorders may be predisposed to 18‐21 .…”

Testing association of rare genetic variants with resistance to three common antiseizure medications

“…The response rates of the more than 20 approved ASMs do not seem to differ considerably, although head‐to‐head comparisons are few . The superiority of ethosuximide and valproic acid (VPA) compared with lamotrigine (LTG) in people with childhood absence epilepsy (CAE), or of VPA compared with LTG and topiramate in people with genetic generalized epilepsy (GGE) or juvenile myoclonic epilepsy (JME), are exceptions to this rule. Considering the retention rate of ASMs, other studies favor LTG and levetiracetam (LEV) because of their superior tolerability .…”

Principles of Epilepsy Management for Women in Their Reproductive Years

“…It is important to note that there are some patients, particularly those with generalized forms of epilepsy such as Juvenile Myoclonic Epilepsy or Absence Epilepsy, in whom ASMs such as lamotrigine and levetiracetam may not be as effective in controlling seizures as VPA (35,36). If the patient's seizures are not controlled by less teratogenic ASMs and VPA needs to be used, it is important to find the lowest effective dosage of this ASM to reduce the chances of MCMs as well as cognitive and behavioral deficits.…”