Behavioral side-effects of levetiracetam in children with epilepsy: A systematic review

Halma, Elisabeth; Louw, A.J.A. de; Klinkenberg, Sylvia; Aldenkamp, Albert P.; IJff, Dominique M.; Majoie, Marian

doi:10.1016/j.seizure.2014.06.004

Cited by 85 publications

(57 citation statements)

References 45 publications

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“…A further AE associated with LEV was nervousness/irritability, which has already been reported in a previous systematic review of open label studies aimed at assessing behavioural effects of LEV in children [16]. Psychiatric effects, such as anxiety, depression and psychosis, were very rarely M a n u s c r i p t associated with LEV in RCTs.…”

Section: A N U S C R I P Tmentioning

confidence: 69%

The adverse event profile of levetiracetam: A meta-analysis on children and adults

Verrotti

Prezioso

Sabatino

et al. 2015

Seizure

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Section: A N U S C R I P Tmentioning

confidence: 69%

The adverse event profile of levetiracetam: A meta-analysis on children and adults

Verrotti

Prezioso

Sabatino

et al. 2015

Seizure

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“…[25][26][27] Future research could examine whether the symptoms of CD we observed in prenatally LEV-exposed children have the same pharmacological mechanisms as those in individuals taking LEV for epilepsy. [25][26][27] Future research could examine whether the symptoms of CD we observed in prenatally LEV-exposed children have the same pharmacological mechanisms as those in individuals taking LEV for epilepsy.…”

Section: Discussionmentioning

confidence: 99%

“…The use of LEV in people with epilepsy is associated with an increase in behavioral problems, including aggressive behavior. [25][26][27] Future research could examine whether the symptoms of CD we observed in prenatally LEV-exposed children have the same pharmacological mechanisms as those in individuals taking LEV for epilepsy. Alternatively, this could be related to exposure of the child to maternal behavioral problems at home.…”

Section: Discussionmentioning

confidence: 99%

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy

et al. 2019

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ObjectiveTo examine the behavioral functioning of children prenatally exposed to carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproate (VPA) monotherapy.MethodsIn collaboration with the European Registry of Antiepileptic Drugs and Pregnancy (EURAP), the Dutch EURAP & Development study was designed, a prospective observational study. Between January 2015 and March 2018, the Child Behavior Checklist and the Social Emotional Questionnaire were used to examine the nature and severity of behavioral problems. VPA‐exposed children were compared to children exposed to CBZ, LTG, or LEV, taking potential confounders into account. A direct comparison was also made between LTG and LEV, as these are first‐choice treatments for many women with epilepsy of childbearing potential.ResultsOf the 405 invited, 181 children were included; 26 were exposed to VPA, 37 to CBZ, 88 to LTG, and 30 to LEV. For most children, both parents completed the behavioral questionnaires. Across all four antiepileptic drug (AED) exposure groups, high percentages of children with clinically relevant behavior problems were found, with behavioral problems occurring in 32% of VPA‐exposed children, 14% of CBZ, 16% of LTG, and 14% of LEV. After controlling for potential confounders, VPA‐exposed children had significantly more social problems than those exposed to LTG (−2.8, 95% confidence interval [CI] = −5.2 to −0.4; P = 0.022) or LEV (−3.2, CI: −6.1 to −0.3; P = 0.028), and significantly more attention problems than LEV‐exposed children (−3.7, CI: −6.7 to −0.8; P = 0.013). LTG‐exposed children had significantly more attention deficit (−9.2, CI: −17.3 to 1.1; P = 0.026), but significantly less anxious behavior when compared to LEV‐exposed children (9.0, CI: 0.3‐17.6; P = 0.042).SignificanceCompared to population norms, a high proportion of children of mothers with epilepsy exposed prenatally to monotherapy with four common AEDs had clinical behavioral problems reported by parents. Different patterns were seen, with some but not all subscales raised for all AED exposure groups. It is important that prenatally AED‐exposed children are regularly screened for behavioral problems so that appropriate help can be provided.

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“…Notably, cognitive side effects (eg, fatigue, cognitive slowing) have been documented for older generation AEDs (eg, phenobarbital, valproic acid) and behavioral side effects (eg, irritability, aggression) for newer generation AEDs (eg, levetiracetam, gabapentin) . Levetiracetam is known to have an adverse behavioral side effect profile, with general behavioral problems (19%) and irritability (2.6%) noted in monotherapy, and irritability (4.7%), hyperexcitability (4.4%), and aggression (2.7%) noted in adjunctive use . To date, predictors of AED behavioral side effect tolerability in pediatric epilepsy is not well established .…”

Section: Introductionmentioning

confidence: 99%

Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy

et al. 2017

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SummaryObjective: To examine baseline psychological functioning and antiepileptic drug (AED) behavioral side effects in new onset epilepsy and determine, by age, whether baseline psychological functioning predicts AED behavioral side effects 1 month following AED initiation. Methods: A retrospective chart review was conducted between July 2011 and December 2014 that included youths with new onset epilepsy. As part of routine interdisciplinary care, caregivers completed the Behavior Assessment System for Children, 2nd Edition: Parent Rating Scale to report on baseline psychological functioning at the diagnostic visit and the Pediatric Epilepsy Side Effects Questionnaire to identify AED behavioral side effects at the 1-month follow-up clinic visit following AED initiation. Children (age = 2-11 years) and adolescents (age = 12-18 years) were examined separately.Results: A total of 380 youths with new onset epilepsy (M age = 8.9 AE 4.3 years; 83.4% Caucasian; 34.8% focal epilepsy, 41.1% generalized epilepsy, 23.7% unclassified epilepsy) were included. Seventy percent of youths had at-risk or clinically elevated baseline psychological symptoms. Children had significantly greater AED behavioral side effects (M = 25.08 AE 26.36) compared to adolescents (M = 12.36 AE 17.73), regardless of AED. Valproic acid demonstrated significantly greater behavioral side effects compared to all other AEDs, with the exception of levetiracetam. Higher hyperactivity/impulsivity at baseline significantly predicted higher AED behavioral side effects 1 month after AED initiation in both age groups. Significance: Younger children seem to be more prone to experience behavioral side effects, and these are likely to be higher if youths with epilepsy have baseline hyperactivity/impulsivity. Baseline psychological screening, specifically hyperactivity, can be used as a precision medicine tool for AED selection. K E Y W O R D Santiepileptic drug side effects, hyperactivity, impulsivity, new onset epilepsy

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Behavioral side-effects of levetiracetam in children with epilepsy: A systematic review

Abstract: Based on the findings in this systematic review, children using levetiracetam have a risk of developing several behavioral side-effects such as aggression, hostility and nervousness compared to children who do not use levetiracetam.

Cited by 85 publications

References 45 publications

The adverse event profile of levetiracetam: A meta-analysis on children and adults

The adverse event profile of levetiracetam: A meta-analysis on children and adults

Behavioral problems in children of mothers with epilepsy prenatally exposed to valproate, carbamazepine, lamotrigine, or levetiracetam monotherapy

Antiepileptic drug behavioral side effects and baseline hyperactivity in children and adolescents with new onset epilepsy

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