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. 2011 Jun 15;20(1):81–84. doi: 10.1016/j.jsps.2011.06.001

Efficacy and safety of levetiracetam in pediatric epilepsy

Ahmed A Elberry a,b,⁎, Rawabi K Felemban a, Rawan H Hareeri a, Sawsan M Kurdi a
PMCID: PMC3744971  PMID: 23960780

Abstract

Objective

To evaluate the efficacy and tolerability of Levetiracetam (LEV) as an adjunctive therapy in pediatric patients with different generalized epilepsies.

Design

Chart review of 22 consecutive children age 4–19 years who were treated with LEV for at least 1 year was observed retrospectively. The mean dose rang of LEV was from 250 to 2000 mg. Data were collected on epilepsy type, seizure frequency, concomitant antiepileptic drug and adverse effect.

Results

Of the 22 patient reviewed, 13 (59%) were boys and 9 (41%) were girls. Predominant seizure types were generalized tonic–clonic seizures 13 (59%) and tonic seizure 6 (27%). Other seizure types included myoclonic seizures 2 (9%) and focal seizure 3 (5%). The results showed 10 (45%) had become free of seizure for almost 7 months to 1 year. Eight of these 10 patients (80%) had normalized EEG. Seizure frequency was reduced in 9 (41%) patients and 3 (14%) patients still had seizure. No side effects were reported related to LEV treated patients except for 1 patient.

Conclusion

Our results confirm that LEV may be an effective adjunctive therapy in treatment of childhood epilepsy, especially tonic–clonic seizure, with possible no evident side effect.

Keywords: Epilepsy, Seizure, Pediatric, Levetiracetam

1. Introduction

Epilepsy is the most common serious neurological disorder and is one of the most prevalent noncommunicable diseases in the world (Scott et al., 2001). Control of abnormal neuronal activity with antiepileptic drugs (AEDs) is accomplished by elevating the threshold of neurons to electrical or chemical stimuli or by limiting the propagation of the seizure discharge from its origin (Gidal and Garnett, 2005). Choice of an AED for the treatment of epilepsy in infants and children depends not only on the efficacy of the agent but also in safety, impact on behavior and learning, and existing patient co-morbidities (Sankar, 2005).

Levetiracetam (LEV), an antiepileptic drug, has become widely used in the treatment of several types of epilepsy. It is used as an adjunctive therapy in the treatment of partial onset, myoclonic, and/or primary generalized tonic–clonic seizures (Crest et al., 2004; Kwan et al., 2010). In children, Levetiracetam (LEV) is an antiepileptic drug that is approved for use as adjunct treatment for partial epilepsy in patients aged 4 years and older, as well as for juvenile myoclonic epilepsy in patients aged 12 years and older (Major et al., 2008). Initial performance in standard animal screening models proved disappointing (Klitgaard et al., 1998), but the drug’s success in clinical trials and humans have led some to question whether standard screening models should be reevaluated. For clinicians, LEV was attractive because of its lack of hepatic metabolism, minimal drug interactions, activity against several seizure types, and ability to start an effective dose on day one (Privitera and Cavitt, 2008).

The exact antiepileptic mechanism of LEV is unknown. However, the drug binds to a synaptic vesicle protein, SV2A, which is believed to impede nerve conduction across synapses (Lynch et al., 2004; Rogawski, 2006; Abou-Khalil, 2008). The aim of this study is to evaluate retrospectively the effectiveness of LEV in different types of pediatric epilepsy and its possible side effects.

2. Methods

A retrospective chart review was performed at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia on children with epilepsy who were treated with LEV (Keppra®) from 2005 to 2010. The study was done after approval from KAUH review board and it was conducted to assess the effectiveness and tolerability of LEV as adjunctive therapy in children.

The study was carried out on children diagnosed with epilepsy based on clinical evaluation and electroencephalogram (EEG) abnormalities. All children with associated conditions as developmental delay, brain malformations, and inborn error of metabolism were excluded from the study. The initial study group of 35 was reduced to 22 as a result of insufficient data available in 10 patients and inability of the hospital for providing the drug in 3 patients. Children who were treated with the mean dose range of LEV from 250 to 2000 mg and aged from 4 to 19 years were identified retrospectively. Data were collected on patient age, gender, seizure type, other antiepileptic drugs concomitantly used with LEV, and finally, change in seizure frequency before and after adding LEV.

The starting dose regime of LEV was always introduced 10–15 mg/kg/day once daily. Further dose increases were undertaken in 10 mg/kg/day increments every 2 weeks. The drug was available in tablet form only (250 and 500 mg tablets). The efficacy of LEV treatment with respect to seizure control was classified as <25% seizure reduction, ⩾25% and <50% seizure reduction, ⩾50% and <75% seizure reduction, ⩾75% seizure reduction, and seizure freedom. Adverse effects were obtained retrospectively from the medical record files. Data of the study were analyzed descriptively.

3. Results

The results of the study and the patient data are shown in Table 1. Of the 22 patient reviewed, 13 (59%) were boys and 9 (41%) were girls. The average age was 3–19 years (mean = 10 years). With the exception of 1 patient, all have received concomitant antiepileptic medication. The most common antiepileptic drugs included topiramate, valproate, lamotrigine, clonazepam, vigabatrin, carbamazepine and phenobarbital.

Table 1.

Patient data for those who received levetiracetam (LEV, Keppra®) as adjuvant therapy.

ID Age (year)/gender Type of seizure Concomitant medications Mean LEV dose (mg) Duration use of LEV (year) Seizure frequency after LEV Side effect
1 4/F Generalized tonic clonic Topiramate 125 mg OD 250 2.5 Seizure free for more than year with normalized EEG None
Clonazepam
2 Drops BID
Vit B6 40 mg BID
Valproic acid 1.5 ml BID
2 4/M Tonic convulsion Topiramate 25 mg OD 500 1 Seizure free for more than 10 months with normalized EEG None
3 4/F Tonic convulsion Clonazepam 2 drops TID 250 1 Decreased frequency of seizure None
Topiramate 25 mg BID
4 4/M Tonic convulsion Lamotirgine 10 mg BID 250 2 Still has seizures None
Topiramate 25 mg BID
5 5/M Myoclonic seizures Valproic acid 150 BID 500 2 Decreased frequency of seizure None
6 6/F Generalized tonic clonic Valproic acid 15 mg BID 500 1 Seizure free with normalized EEG None
Clonazepam 2 drops BID
7 6/F Myoclonic seizures Topiramate 25 mg am 250 2 Still have seizure Change in attitude and behavior and loss of appetite
50 mg pm
Vigabatrin 250 mg BID
8 6/M Tonic convulsion Valproic acid 5 ml BID 250/500 1 Decreased frequency of seizure (but still have some attacks every 1–2 weeks) None
Carbamazepine 25 ml BID
9 9/M Generalized tonic clonic Lamotirgine 50 mg BID 750 2 Seizure free for more than 1 year with normalized EEG None
Carbamazepine 3 ml TID
10 9/M Generalized tonic clonic Topiramate 100 BID 500 2.5 Seizure free for 7 months with normalized EEG None
11 9/M Generalized tonic clonic Topiramate 100 mg BID 1000 3 Seizure free for 1 year with normalized EEG None
12 10/M Tonic convulsion Lamotirgine 50 mg BID 250 5 Seizure free for 8 months None
Topiramate 50 mg BID
13 10/M Generalized tonic clonic Non 500 2 Still have seizure None
14 11/F Generalized tonic clonic Carbamazepine 300 mg BID 1000 1.5 Seizure free for more than 1 year with normalized EEG None
Topiramate 75 mg BID
15 12/F Rt side focal convulsions Convulsions Topiramate 100 mg am 1000 1 Decreased frequency of seizure (one seizure per month) None
200 mg pm
Carbamazepine 400 mg BID
16 14/F Generalized tonic clonic Carbamazepine 400 mg am 1000 1 Decreased frequency of seizure None
200 mg pm
17 14/F Generalized tonic clonic Lamotirgine 75 mg BID 1000 5 Decreased frequency of seizure None
Phenobarbital 50 mg BID
18 18/M Generalized tonic clonic Valproic acid 500 mg BID 500 1.5 Decreased frequency of seizure None
Lamotirgine 100 mg BID
19 18/M Generalized tonic clonic Lamotirgine 50 mg BID 1000 4 Seizure free for more than 8 months None
Valproic acid 5 ml BID
20 18/M Generalized tonic clonic Valproic acid 500 mg BID 2000 2 Decreased frequency of seizure None
Lamotirgine 100 mg BID
21 18/F Tonic convulsion Topiramate 125 mg BID 1000 3 Decreased frequency of seizure None
Valproic acid 500 mg BID
22 19/M Generalized tonic clonic Topiramate 100 mg BID 1000 2 Seizure free for more than 8 month with normalized EEG None
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Predominant seizure types were generalized tonic–clonic seizures 13 (59%) and tonic seizure 6 (27%). Other seizure types included myoclonic seizures 2 (9%) and focal seizure 3 (5%).

The mean dosage range of LEV was 250–2000 mg and the duration of treatment ranged from 1 to 5 years.

Of the 22 patients, 10 (45%) had become free of seizure for almost 7 months to 1 year especially in those with tonic–clonic convulsions. Eight of these 10 patients (80%), had normalized EEG. Seizure frequency was reduced in 9 (41%) patients and 3 (14%) patients still had seizure (Fig. 1). There was no prominent side effect related to LEV except for one patient (5%) who was coadministered vigabatrin where the patient has recorded change in attitude and behavior with loss of appetite.

Figure 1.

Figure 1

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Patient outcome treated with levetiracetam (LEV).

4. Discussion

Epilepsy is a common chronic disorder that requires long-term antiepileptic drug therapy. Approximately one half of patients fail the initial antiepileptic drug and about 35% are refractory to medical therapy, highlighting the continued need for more effective and better tolerated drugs (Abou-Khalil, 2008). LEV has been demonstrated effective as adjunctive therapy for refractory partial-onset seizures, primary generalized tonic–clonic seizures, and myoclonic seizures (Major et al., 2008; Abou-Khalil, 2008).

The current study showed that seizure frequency was reduced in 41% of pediatric patients who used LEV. Moreover, 45% of the patients had become seizure free for almost 7 months to 1 year with normalization of EEG in 80% of these patients. This finding is consistent with a previous study which revealed that LEV appeared to be effective in decreasing epileptiform EEG abnormalities (Specchio et al., 2008). Most of the seizure types were found to be of tonic–clonic type. Preliminary evidence by Verrotti et al. (2008) revealed that LEV may be effective for treating 32 adolescent patients with newly diagnosed Juvenile myoclonic epilepsy (JME). Verrotti and his colleagues found at 6-month evaluation: 15 patients were seizure free; 14 patients were responders (>50% reduction in seizures); and three patients had marginal effects (<50% reduction of seizures). At 12-month evaluation: 29 patients were seizure free; three patients were responders with no reported adverse events. Moreover, Specchio et al. (2008) supports a first-line role for LEV in the treatment of JME. Consistently, Stephen et al. (2011) found that seizure freedom was achieved in around half adult patients on a median LEV dose of 1000 mg/day. On the other hand, most previous studies of children treated with LEV demonstrated seizure-freedom rates from 5% to 23%, with total duration of seizure freedom ranging from 1 to 38 months (Wheless and Ng, 2002; Lagae et al, 2003). Koukkari and Guarino (2004) studied the effect of LEV in childhood seizure disorders that included 50 patients with partial and generalized seizures. The study showed 12 had ⩾75% seizure reduction, 3 had ⩾50% and <75% seizure reduction, 8 had ⩾25% and <50% seizure reduction, and 27 had <25% seizure reduction. In addition, Perry and Benatar (2007) showed that 57% of the patients experienced at least some duration of seizure freedom, with a median duration of clinical response of 8.9 months. 80% of those patients who became seizure free maintained seizure freedom in excess of 6 months. This finding was in accordance with the current study that showed 45% of patients had become seizure free for almost 7 months to 1 year.

No adverse events associated with LEV were documented in this study except for one child where he experienced change in attitude and behavior and loss of appetite which may be attributed to either vigabatrin or LEV. Major et al., suggested the possible efficacy of pyridoxine supplementation in the treatment of LEV-induced behavioral side effects (Major et al., 2008). On the other hand, the observed adverse event profile of LEV among pediatric patients in previous studies were mainly related to the central nervous system, and the most frequent was somnolence, asthenia, dizziness, and behavioral difficulties (Shorvon et al, 2000; Ben-Menachem and Falter, 2000; Glauser et al., 2002; Sirsi and Safdieh, 2007).

5. Conclusion

In conclusion, the present study showed that LEV may be an effective adjunctive therapy in treatment of childhood epilepsy, especially tonic–clonic seizure, with possible no evident side effect.

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