Seizure 19 (2010) 195197

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Short communication

Long-term efcacy of valproate versus lamotrigine in treatment of idiopathic

generalized epilepsies in children and adolescents
Maria Mazurkiewicz-Bedzinska *, Marta Szmuda, Agnieszka Matheisel
Department of Developmental Neurology, Chair of Neurology, Medical University of Gdansk, Poland

A R T I C L E I N F O

A B S T R A C T

Article history:
Received 11 October 2009
Received in revised form 19 January 2010
Accepted 22 January 2010

Purpose: In order to estimate and compare the long-term effectiveness of lamotrigine (LTG) versus
valproate (VPA) monotherapy in treatment of newly diagnosed idiopathic generalized epilepsies (IGE)
the following study was performed.
Methods: Medical records of 214 children and adolescents suffering from IGE were analyzed. 132 of
them were on VPA monotherapy, 82 on LTG. The majority of patients had juvenile myoclonic epilepsy
98, the rest: juvenile absence epilepsy 32, childhood absence epilepsy 53 and epilepsy with a tonic
clonic seizures on awakening 12, others 19. Mean age of the patients was 8.9 years (range 416
years). The mean time of treatment was 28 months, time of observation 40 months. In order to estimate
retention rates and factors predicting successful treatment with LTG and VPA we used KapplanMeyer
analysis and Gehan tests.
Results: Data analysis showed signicantly longer retention rates with VPA versus LTG treatment in
overall rates as well in all syndromes subgroups. After 12 months of therapy 69% stayed on LTG therapy
versus 89% on VPA, after 24 months 57% versus 83% respectively. VPA showed comparable efcacy in all
IGE syndromes where LTG showed better efcacy in childhood and juvenile absence epilepsy than in
juvenile myoclonic epilepsy. The shorter duration of treatment with LTG was due to lack of efcacy.
Conclusions: Our results show the superiority of VPA versus LTG treatment in idiopathic generalized
epilepsy syndromes.
2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Keywords:
Idiopathic generalized epilepsy
Lamotrigine
Valproate

1. Introduction
Idiopathic generalized epilepsies (IGE) are genetically determined and affect otherwise normal people of both sexes and races.
They manifest with generalized tonicclonic seizures, typical
absence seizures and myoclonic jerks alone or in varying
combinations and severity. In general IGE respond to treatment,
with approximately 80% becoming fully controlled 1. Monotherapy
is considered to be the goal in the rst line pharmacologic
management of epilepsy as it is effective, well tolerated and
associated with low costs, better patient compliance and higher
quality of life. Although conventional anti-epileptic drug (AED)
valproate and the modern AED lamotrigine are identied as
optimal rst line or second-line monotherapy for idiopathic
generalized epilepsies, effectiveness and course of treatment vary
between the patients and are still a matter of discussion.
Lamotrigine has been proposed as rst line new AED in treatment

* Corresponding author. Tel.: +48 583492396; fax: +48 583492395.

E-mail addresses: mmazur@amg.gda.pl, mazur@amg.gda.pl
(M. Mazurkiewicz-Bedzinska), mgkgs@wp.pl (M. Szmuda), ajuzwa@amg.gda.pl
(A. Matheisel).

of childhood absence, juvenile absence, juvenile myoclonic and

generalized tonicclonic epilepsy according to NICE guidelines 2.
Valproate is a very effective anticonvulsant drug (AED) for IGE
however it carries some risks connected with its side effects
prole. There is still limited evidence with head to head
comparision of this two agents in clinical settings 3. The goal of
present study was to estimate and compare the long-term
effectiveness of lamotrigine (LTG) versus valproate (VPA) monotherapy in treatment of idiopathic generalized epilepsies (IGE).
2. Materials and methods
Medical records of 214 children and adolescents suffering from
IGE (patients of Developmental Neurology Department and
Outpatient Clinic during 19992008) were analyzed. All of the
patients were newly diagnosed with IGE and previously not
treated. 132 of them were on VPA monotherapy, 82 on LTG. The
majority of patients had juvenile myoclonic epilepsy 98, juvenile
absence epilepsy 32, childhood absence epilepsy 53 and
epilepsy with a tonicclonic seizures on awakening 12, others
19 (included 4 patients presenting absences with eyelid myoclonias, 5 with myoclonic absences and 10 who did not fulll criteria
for pure childhood absence epilepsy (photosensitivity, early in

1059-1311/$ see front matter 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.seizure.2010.01.014

M. Mazurkiewicz-Bedzinska et al. / Seizure 19 (2010) 195197

196
Table 1
Group characteristics.
LTG

VPA

Number of patients
Males/Females
Mean age of seizure onset
Mean weight (kg)

82
27/55
8.5 (416)
32,2 (17.2101)

132
62/70
9.2 (416)
27.1 (18.572.2)

Types of epileptic seizures

Myoclonic
Absence
Tonicclonic

39
41
25

82
59
32

Types of epilepsy syndrome

Juvenile myoclonic epilepsy (JME)
Childhood absence epilepsy (CAE)
Juvenile absence epilepsy (JAE)
Epilepsy with tonicclonic
seizures on awakening

35
21
15
7

63
32
17
5

Others

15

Note: Some patients had more than one type of epileptic seizure.
Fig. 1. Retention rates lamotrigine versus valproate in idiopathic generalized
epilepsies.

the course of disease appearance of tonicclonic seizures). Mean

age of the patients was 8.9 years (range 416 years). The group
characteristics are presented in Table 1. The mean time of
treatment was 28 months, time of observation 40 months. Mean
doses of LTG were 8 mg/kg/day (range 513 mg/kg/day), for VPA
25 mg/kg/day (range 2032 mg/kg/day). In order to estimate
retention rates and factors predicting successful treatment with
LTG and VPA we used KapplanMeyer analysis and Gehan tests.
3. Results
Data analysis showed signicantly longer retention rates with
VPA versus LTG treatment in overall rates as well in major
syndromes subgroups. After 12 months of therapy 69% of patients
stayed on LTG therapy versus 89% on VPA, after 24 months 57%
versus 83% respectively (Fig. 1). VPA showed comparable efcacy in
all IGE syndromes, where LTG showed better efcacy in childhood
and juvenile absence epilepsy than in juvenile myoclonic epilepsy
(Table 2). The shorter duration of treatment with LTG was due to
lack of efcacy (Table 3). There were no differences in mental status
as well as severity of EEG changes in subgroups of patients who
continued or discontinued the treatment. Side effects were
important reasons for discontinuation of the therapy. 10 patients
receiving VPA ceased the treatment because of: weight gain, hair
loss, diarrhoea, stomach pain. 2 patients treated with LTG
discontinued further treatment due to rash.

4. Discussion
Our study is one of the few comparing the retention rates of
new AEDLTG with classical AEDVPA, that has well established
efcacy in this type of epilepsy. This is an observational study
performed in a single centre, thus there was no risk of
methodological differences which could be present in studies
where patients from several referral centers are included. It seems
to be important, that all the patients were not previously treated
with any AED.
The sample group is relatively large and we hope that the
results reect the reality in clinical practice. The VPA and LTG
groups, as well as the subgroups of different epileptic syndromes
(JME, CAE, JAE) were similar according to age. There were
signicantly more females in LTG group. LTG was prescribed
especially to girls because of potential lack of adverse events
crucial for female-teenagers such as hyperandrogenism and
potential teratogenity 48 as well for patients who were overweight
or had a tendency to gain on weight.
Long-term tolerability of AEDs in children is important, because
the adverse event prole of the drug is often a major determinant
in the choice of therapy.
However, in our study better tolerability and relatively small
rate of side effects did not correlate with longer period of therapy.
Principal reason of earlier discontinuation of therapy in LTG group
was referred to lower efcacy in comparison to VPA group.

Table 2
Mean duration (months) of treatment for all patients with IGE and according to major types of epilepsy syndromes (JME juvenile myoclonic epilepsy or CAE childhood
absence epilepsy).
All patients

VPA
LTG

JME

CAE

Number of patients

Mean

Range

Number of patients

Mean

Range

Number of patients

Mean

Range

132
82

34.6
19.2

169
157

63
35

38.1
8.4

169
142

32
21

39.8
26.1

169
157

Table 3
Reason of discontinuation of lamotrigine and valproate in patients with idiopathic generalized epilepsy and mean duration (months) of treatment in patients who
discontinued the drug.

Valproate
Lamotrigine

Discontinued (number of patients) (%)

Mean duration of treatment

Lack of efcacy

Adverse effects

Others

Lost to follow up

28/19.7
47/57.3

12.3
9.7

14
39

10
2

2
3

2
3

M. Mazurkiewicz-Bedzinska et al. / Seizure 19 (2010) 195197

We nd it noteworthy that valproate provides good long-term

maintenance of seizure control. At the same time, we did not nd
the support to previous statements that lamotrigine could serve as
alternative treatment to valproate in forms of IGE 914.
Comparability is never perfect in a non-randomized study, but it
is unlikely that the differences in outcomes could be a result of using
inappropriate doses of some AED. The doses of the AED surveyed in
the study were within the recommended target levels 15. This study
was not a controlled trial and in these patients drugs were normally
adjusted depending on the efcacy and the tolerability.
The duration of treatment with AED (retention rate) strongly
associates with two major factors the efcacy and the adverse
events. In many cases a prot of successful treatment of epilepsy
which means reduction or even elimination of seizuresoverweighs the expense of adverse effects. For this reason, further
comparable long-term studies should be performed in order to
assess the signicance of side effects in particular age groups of
patients with marked improvement on valproate therapy.
Discontinuations of AED owing to adverse effects occurred
quite early in the course of treatment, usually within the rst six
months. In our study adverse effects were the reason of
discontinuation in 5.6% of patients (7.6% on VPA and 2.4% on
LTG). It shows, that LTG was better tolerated but the lack of efcacy
was crucial for the smaller retention rate with this drug. 47.6% of
patients on LTG discontinued the study due to lack of efcacy
versus 10.6% on VPA therapy.
Data in the literature suggests that the primary reason for fail
the newly introduced anti-epileptic treatment is a lack of efcacy
rather than adverse effects. Proper decision of neurologist is
essential as inadequate response to initial treatment is believed to
be a poor prognostic factor in further course of epilepsy 16.
Especially for children and adolescents it is extremely important to start the therapy with the drug, that provides the patient a
greater chance for being seizure free (between others, also from
the social and psychological point of view). It is important to
mention that in long-term therapy with VPA it is possible to
maintain the therapeutic effect on reduced dose with the benet of
reduced adverse effects including teratogenicity 17.
5. Conclusions
In conclusion, our study suggests that there are clinically
signicant differences between lamortrigine and valproate in

197

terms of efcacy in idiopathic generalized epilepsies. Furthermore,

our study supports the value of retention rate studies in assessing
outcome of the drugs in clinical practice.
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