Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

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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.

Original languageEnglish
Pages (from-to)420-430
Number of pages11
JournalEpilepsia Open
Volume4
Issue number3
DOIs
Publication statusE-pub ahead of print/First online - 26 Jun 2019

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Juvenile Myoclonic Epilepsy
Valproic Acid
Anticonvulsants
etiracetam
Carbamazepine
Drug-Related Side Effects and Adverse Reactions
Proportional Hazards Models
Seizures
Lethargy
Tremor
Epilepsy

Keywords

  • adverse drug reactions
  • seizures
  • tolerability
  • valproate

Cite this

@article{bfbfeb96201c4112a62833b9a722276c,
title = "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.",
keywords = "adverse drug reactions, seizures, tolerability, valproate",
author = "Katri Silvennoinen and {de Lange}, Nikola and Sara Zagaglia and Simona Balestrini and Ganna Androsova and Merel Wassenaar and Pauls Auce and Andreja Avbersek and Felicitas Becker and Bianca Berghuis and Ellen Campbell and Antonietta Coppola and Ben Francis and Stefan Wolking and Cavalleri, {Gianpiero L.} and John Craig and Norman Delanty and Johnson, {Michael R.} and Koeleman, {Bobby P.C.} and Kunz, {Wolfram S.} and Holger Lerche and Marson, {Anthony G.} and O’Brien, {Terence J.} and Sander, {Josemir W.} and Sills, {Graeme J.} and Pasquale Striano and Federico Zara and {van der Palen}, Job and Roland Krause and Chantal Depondt and Sisodiya, {Sanjay M.} and Brodie, {Martin J.} and Krishna Chinthapalli and {de Haan}, {Gerrit Jan} and Doherty, {Colin P.} and Sinead Heavin and Mark McCormack and Slav{\'e} Petrovski and Narek Sargsyan and Lisa Slattery and Joseph Willis",
year = "2019",
month = "6",
day = "26",
doi = "10.1002/epi4.12349",
language = "English",
volume = "4",
pages = "420--430",
journal = "Epilepsia Open",
issn = "2470-9239",
publisher = "Wiley-Blackwell",
number = "3",

}

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy. /.

In: Epilepsia Open, Vol. 4, No. 3, 26.06.2019, p. 420-430.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy

AU - Silvennoinen, Katri

AU - de Lange, Nikola

AU - Zagaglia, Sara

AU - Balestrini, Simona

AU - Androsova, Ganna

AU - Wassenaar, Merel

AU - Auce, Pauls

AU - Avbersek, Andreja

AU - Becker, Felicitas

AU - Berghuis, Bianca

AU - Campbell, Ellen

AU - Coppola, Antonietta

AU - Francis, Ben

AU - Wolking, Stefan

AU - Cavalleri, Gianpiero L.

AU - Craig, John

AU - Delanty, Norman

AU - Johnson, Michael R.

AU - Koeleman, Bobby P.C.

AU - Kunz, Wolfram S.

AU - Lerche, Holger

AU - Marson, Anthony G.

AU - O’Brien, Terence J.

AU - Sander, Josemir W.

AU - Sills, Graeme J.

AU - Striano, Pasquale

AU - Zara, Federico

AU - van der Palen, Job

AU - Krause, Roland

AU - Depondt, Chantal

AU - Sisodiya, Sanjay M.

AU - Brodie, Martin J.

AU - Chinthapalli, Krishna

AU - de Haan, Gerrit Jan

AU - Doherty, Colin P.

AU - Heavin, Sinead

AU - McCormack, Mark

AU - Petrovski, Slavé

AU - Sargsyan, Narek

AU - Slattery, Lisa

AU - Willis, Joseph

PY - 2019/6/26

Y1 - 2019/6/26

N2 - 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.

AB - 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.

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KW - seizures

KW - tolerability

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