Lamotrigine as adjunctive therapy in patients with refractory
epilepsy and mental retardation
and P.S. Barrett
Pharmacy Department, Western Carolina Center, 300 Enola Road, Morganton, NC 28655, USA
Southern Illinois University School of Medicine, Springﬁeld, IL, USA
New York University School of Medicine, New York, NY, USA
GlaxoSmithKline, Research Triangle Park, NC, USA
Received 9 October 2002; revised 6 March 2003; accepted 19 April 2003
This study evaluated the eﬀects of lamotrigine as adjunctive therapy for refractory epilepsy in patients with mental retardation.
Patients with epilepsy and mental retardation having uncontrolled seizures despite treatment with other antiepileptic drugs were
eligible (n ¼ 67). The open-label study comprised a Baseline Phase, an Escalation Phase during which lamotrigine was titrated to a
target dose, an 8-week Maintenance Phase during which doses of lamotrigine and concomitant antiepileptic drugs were main-
tained, and a 12-week Optimization Phase during which doses of lamotrigine and other antiepileptic drugs could be adjusted.
Almost half (44%) of patients experienced a 50% reduction in seizure frequency during the Maintenance Phase after addition of
lamotrigine; 15% of patients became seizure-free. A similar pattern of results was reported for the Optimization Phase. Investi-
gator-rated clinical status was improved relative to baseline in 66 and 74% of patients at the end of the Maintenance and Op-
timization Phases, respectively. Most patients experienced improvements in seizure frequency, duration, and intensity during the
Maintenance Phase (62 to 72%) and the Optimization Phase (65 to 74%). Many patients were rated as having improved social
functioning during the Maintenance Phase (42%) and the Optimization Phase (46%). The Aberrant Behavior Checklist score for
lethargy and the mean Habilitative Improvement Scale score were improved at the ends of the Maintenance and Optimization
Phases relative to baseline (P 6 0:04). One limitation of this study is its open-label design, which limits the ability deﬁnitively to
attribute the clinical improvements to lamotrigine. Adjunctive lamotrigine in patients with refractory epilepsy and mental re-
tardation appears to decrease seizure frequency and improve behavior while permitting a reduction in dose of concomitant an-
Ó 2003 Elsevier Science (USA). All rights reserved.
Keywords: Lamotrigine; Epilepsy; Mental retardation
Epilepsy and mental retardation, the two most com-
mon neurologic impairments among children, are fre-
quently comorbid [1–4]. The management of epilepsy in
patients with mental retardation poses unique chal-
lenges. First, epilepsy in patients with mental retarda-
tion may be particularly refractory to treatment, and
patients often experience multiple seizure types [5,6].
Because of the refractory nature of the seizures, patients
are frequently maintained on several concomitant an-
tiepileptic drugs with an attendant high risk of drug
interactions and adverse eﬀects. Second, patients with
mental retardation are often more susceptible than
nonretarded individuals to adverse behavioral and psy-
chotropic eﬀects of medications . This heightened
Epilepsy & Behavior 4 (2003) 386–394
This research was funded by GlaxoSmithKline. Portions of the
data described in the article were presented at the 2000 annual meeting
of the American Academy of Neurology and the 2000 and 2001 annual
meetings of the American Epilepsy Society.
Corresponding author. Fax: +828-433-2894.
E-mail address: firstname.lastname@example.org (J.R.
1525-5050/$ - see front matter Ó 2003 Elsevier Science (USA). All rights reserved.