Concomitant use of divalproex sodium and lamotrigine in developmentally disabled patients with epilepsy: a retrospective evaluation of efficacy and tolerability Rama Maganti, a Barry E. Gidal, a,b, * Roland Shaw, d and Paul Rutecki a,c a Department of Neurology, University of Wisconsin, Madison, WI 53705, USA b School of Pharmacy, University of Wisconsin, Madison, WI 53705, USA c Department of Neurosurgery, University of Wisconsin, Madison, WI 53705, USA d Central Wisconsin Center for Developmentally Disabled, Madison, WI 53705, USA Received 28 January 2002; received in revised form 3 May 2002; accepted 6 May 2002 Abstract Objective. Epilepsy in institutionalized severe developmentally disabled patients poses a therapeutic challenge. Frequently these patients have multiple seizure (sz) types that are often intractable. Both divalproex sodium (VPA) and lamotrigine (LTG) have demonstrated efficacy. We sought to examine the efficacy of this specific combination in a group of institutionalized, develop- mentally disabled patients with epilepsy. Methods. Medicalandpharmacyrecordsofallpatientswithdevelopmentaldisabilitiesandintractableseizureswerereviewedto identify those who had received VPA and LTG. This retrospective evaluation was structured with respect to time frame and outcomemeasure.Phase1consistedofbaselinemonotherapywithVPA.Phase2consistedoftitration/doseescalation.Phase3was treatmentobservationperiodwiththecombinationofboth.Seizurefrequencyandadverseeffectdatawereobtainedfromnursingor residentialstaffrecords.PrimaryoutcomemeasureswerechangeinseizurefrequencybetweenPhases1and3.Additionalmeasures were percentage of patients seizure-free and those with >75% reduction in seizures. A Wilcoxan signed rank test was used for statistical analysis. Results. Of293patients,25(12M/13F,31:7  10:2years)hadVPAmonotherapyfollowingwhichLTGwasadded.Meandoses ofVPAandLTGwere1474  728and165  111mg/day,respectively.Baselineseizurefrequencyrangedfrom1to25permonth. Mean seizure frequency significantly decreased (6:5  vs2:0  4:0seizures/month, P < 0:001). Sixty-four percent of these patients had P 75% reduction in seizures 28% became seizure-free. Conclusions. The combination of VPA and LTG appears efficacious in this group of developmentally disabled patients with intractable seizures. Rash, which has been associated with this combination, was notably absent and this may reflect the slower titration schedule used. Ó 2002 Elsevier Science (USA). All rights reserved. Keywords: Developmentally disabled; Epilepsy; Valproate; Lamotrigine 1. Introduction Epilepsy is commonly encountered in developmen- tally disabled patients, with the incidence increasing with the severity of disability [1]. Evaluation and treat- ment of epilepsy in these patients are complex as pa- tients may present with multiple seizure types including partial and generalized seizures. Frequently these sei- zures are intractable to treatment with older antiepi- leptic drugs (AEDs) [2,3]. In patients with developmental handicaps, the ideal therapeutic ap- proach would be mono- or combination AED therapy that demonstrates efficacy against both partial and generalized seizures, has minimal cognitive and behav- ioral adverse effects, and has minimal or at least pre- dictable, pharmacokinetic interactions [4]. In this population, polytherapy with older AEDs, including bothenzyme-inducingagentsandinhibitors(divalproex sodium), is common [5]. Epilepsy & Behavior 3 (2002) 275–279 www.academicpress.com Epilepsy & Behavior * Corresponding author. Fax: 608-265-5421. E-mail address: begidal@pharmacy.wisc.edu (B.E. Gidal). 1525-5050/02/$ - see front matter Ó 2002 Elsevier Science (USA). All rights reserved. PII:S1525-5050(02)00028-8