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Concomitant lamotrigine use is associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy

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Effects of concomitantly used AEDs on the success rate of the KD at three months (van der LouW et al., 2015)
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M van der Louw, E. J. T., Desadien, R., Vehmeijer, F. O. L., van der Sijs, H., Catsman-Berrevoets, C. E., & Neuteboom, R. F. (2015). Concomitant lamotrigine use is associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy. Seizure. doi:10.1016/j.seizure.2015.09.007
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A retrospective study on 71 children with refractory epilepsy looking at the effect of concomitant AED use on the efficacy of the ketogenic diet (KD), has suggested that Lamotrigine used alongside significantly reduced the efficacy of the diet (van der LouW et al., 2015).

The study was performed by van der LouW and colleagues at Erasmus University Hospital Sophia Children's Hospital, Rotterdam and published in the journal Seizure on 21 September 2015. The study included children aged 0-18 yrs. who were started on KD between 2008-2014 and were on the diet for at least 3 months and were also on other AEDs. The authors defined success of the ketogenic diet as > 50% seizure reduction at three months after start of the diet compared to baseline.

In the study 43/71 (61%) children achieved >50% seizure reduction within three months while in 39% (n = 28) the KD was not efficacious. Failure of the KD was significantly associated with the failure to achieve adequate ketosis. The concomitant use of lamotrigine alone or in polytherapy significantly reduced the likelihood of >50% reduction in seizures after 3 months of KD. The adjuvant use of other AEDs studied, Valproic acid, levetiracetam, clobazam or vigabatrin did not seem to negatively influence the efficacy of the diet.

These findings are in keeping with a 2009 retrospective study of 217 children from John Hopkins University School which suggested a reduced efficacy of KD with lamotrigine although the results were not statistically significant. In contrast the John Hopkins study had also shown reduced efficacy for KD with phenobarbital and an increased efficacy with Zonisamide (Morrison et al., 2009).

The authors give several possible explanations for these findings including the induction of UDP glucuronosyltransferase 1 family, polypeptide A6 (UGT1A6) enzyme activity by the Ketogenic diet which increased the glucuronidation of lamotrigine to its inactive metabolites, the interaction between ketones and lamotrigine on glutamate neurotransmitter release or lamotrigine specifically interfering with the formation of ketones. The current study by van der LouW et al highlights the implications on lamotrigine use alongside ketogenic diet and suggest that levels of lamotrigine and its metabolites should be measured, and doses adjust or treatment discontinued if adequate ketone levels are not achieved.

Further research is required to investigate the interactions of specific AEDs with the ketogenic diet

Citation:

M van der Louw, E. J. T., Desadien, R., Vehmeijer, F. O. L., van der Sijs, H., Catsman-Berrevoets, C. E., & Neuteboom, R. F. (2015). Concomitant lamotrigine use is associated with decreased efficacy of the ketogenic diet in childhood refractory epilepsy. Seizure. doi:10.1016/j.seizure.2015.09.007

Morrison PF, Pyzik PL, Hamdy R, Hartman AL, Kossoff EH (2009) The influence of concurrent anticonvulsants on the efficacy of the ketogenic diet. Epilepsia 50 (8):1999-2001. DOI:10.1111/j.1528-1167.2009.02053.x PMID: 19389152.

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