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Epilepsia. 2009 Mar;50(3):475-9. doi: 10.1111/j.1528-1167.2008.01866.x. Epub 2008 Nov 19.

Lamotrigine-valproic acid combination therapy for medically refractory epilepsy.

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Department of Medicine, Division of Neurology, Dalhousie University, Halifax, Nova Scotia, Canada.



A retrospective study of lamotrigine (LTG)-valproic acid (VPA) combination therapy in medically refractory epilepsy.


Patients were identified with an adult epilepsy clinic database and were included if they had been on LTG-VPA combination therapy for at least 6 months. Patient demographics and information about epilepsy type, severity, and degree of medical intractability were obtained by retrospective chart review. The primary outcome measure was change in baseline seizure frequency, and patients were stratified into three groups: (i) seizure-free, (ii) improved (at least 50% reduction in baseline seizure frequency), and (iii) not improved.


Thirty-five patients met all inclusion-exclusion criteria. Epilepsy type was generalized in 25 patients (71%) and partial in 10 patients (29%). Before LTG-VPA treatment, 27 of 35 (77%) experienced disabling seizures on a monthly basis, and 17 of 35 (49%) of patients had at least one disabling seizure per week. Patients had previously failed treatment with a median of five antiepileptic drugs (AEDs), alone or in combination. With LTG-VPA therapy, 18 (51.4%) remained completely seizure-free, four (11.4%) were improved, and 13 (37.1%) were unimproved. Median follow-up was 42 months. Of the 22 patients who improved, 11 had previously failed LTG and VPA monotherapy. There was no significant difference between improved and unimproved patients with respect to demographics, epilepsy type or severity, or number of previously failed AEDs.


The combination of LTG and VPA should be considered in patients with medically refractory epilepsy. The effectiveness of this combination appears to be independent of epilepsy type or patient demographics.

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