The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet Peter F. Morrison, Paula L. Pyzik, Rana Hamdy, Adam L. Hartman, and Eric H. Kossoff The Johns Hopkins Hospital, Baltimore, MD, U.S.A. SUMMARY It is unknown if any particular anticonvulsants modify the likelihood of seizure reduction when used in combination with the ketogenic diet (KD). A retrospective study was performed of 217 consecutive children who started the KD from 2000–2007. Patients included did not have any changes to their anticonvulsant dose. Efficacy data at 3 months on the KD were analyzed with respect to the six most frequently used anticonvulsants in this cohort. A total of 115 patients were included. Children receiving phenobarbital in combination with the KD were significantly less likely to have a >50% seizure reduction (p = 0.003). Conversely, those receiving zonisamide in combination with the KD at onset were more likely to have a >50% reduction (p = 0.04). These results provide practi- cal information to clinicians who are treating chil- dren receiving both the KD and anticonvulsants. KEY WORDS: Ketogenic, Diet, Anticonvulsants, Children, Epilepsy. The ketogenic diet (KD) is a high-fat, adequate protein, low-carbohydrate diet used as a treatment for refractory epilepsy in the pediatric population (Freeman et al., 2007). When the KD is started, the majority of children are receiving one or more concurrent anticonvulsant medica- tions. However, one of the most common reasons for implementing the KD other than seizure control is to reduce and discontinue anticonvulsants (Farasat et al., 2006). At this time, it is not known which anticonvulsants work better or worse in combination with the KD; nor is it known which should be discontinued first. There does not appear to be an increased likelihood of adverse effects with the KD in combination with valproate (Lyczkowski et al., 2005), topiramate (Kossoff et al., 2002a; Takeoka et al., 2002), or zonisamide (Kossoff et al., 2002a). Similarly, there is no clear evidence of anticonvulsant synergy with the KD, although the vagus nerve stimulator may be a nonpharmacologic therapy that works well with the KD (Kossoff et al., 2007). An animal model has suggested that the KD plus high-dose valproic acid work synergistically to increase seizure threshold in selected acute seizure tests (Bough & Eagles, 2001), but this has not been shown in children. The present study sought to address whether commonly used, typically broad-spec- trum anticonvulsants modify the efficacy of the KD when used together. Methods A retrospective cohort study was performed of 217 con- secutive children who started the KD at Johns Hopkins Hospital from 2000–2007. Children were started on the diet according to a standardized protocol (Freeman et al., 2007). Medical records were reviewed with respect to demographic data, seizure type, epilepsy syndrome, age at seizure and KD onset, seizure frequency, number of anti- convulsants tried prior to starting the KD, and specific an- ticonvulsants taken while on the KD. Based on previous data, we decided to examine outcomes of children on the diet at 3 months to allow for only diet adjustment and the highest likelihood of observing improvement (Kossoff et al., 2008a), but also because most children had medica- tion adjustment by the 6-month diet duration period (Kossoff et al., 2004). Of the 217 children, 153 (71%) who were started on the KD had no anticonvulsant changes in the first 3 months of KD use and were included in this analysis. Twenty patients who discontinued the KD prior to the 3-month assessment point were excluded from analysis due to incomplete information regarding outcomes, with some Accepted December 28, 2008; Early View publication April 6, 2009. Address correspondence to Eric H. Kossoff, M.D., Suite 2158–200 North Wolfe Street, David M. Rubenstein Child Health Building, The John M. Freeman Pediatric Epilepsy Center, The Johns Hopkins Hospi- tal, Baltimore, MD 21287-1000, U.S.A. E-mail: ekossoff@jhmi.edu Wiley Periodicals, Inc. ª 2009 International League Against Epilepsy Epilepsia, 50(8):1999–2001, 2009 doi: 10.1111/j.1528-1167.2009.02053.x BRIEF COMMUNICATION 1999