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ARTICLES: R. M. Pressler, C. D. Binnie, S. G. Coleshill, G. A. Chorley, and R. O. Robinson Effect of lamotrigine on cognition in children with epilepsy Neurology 2006; 66: 1495-1499 [Abstract] [Full text] [PDF]

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Effect of lamotrigine on cognition in children with epilepsy

Igor Prpic, Marko Boban, Inge Vlasic-Cicvaric, Zrinka Korotaj   (25 September 2006)

Reply from the Authors

Ronit M. Pressler, MD, CD Binnie, RO Robinson   (25 September 2006)

Effect of lamotrigine on cognition in children with epilepsy 25 September 2006
Igor Prpic, Department of Pediatrics, University Hospital Centre Rijeka, Med. School, Univ. of Rijeka Brace Branchetta 20, 51 000 Rijeka, Croatia, Marko Boban, Inge Vlasic-Cicvaric, Zrinka Korotaj Send Correspondence to journal: Re: Effect of lamotrigine on cognition in children with epilepsy igorp{at}medri.hr Igor Prpic, et al.	Pressler et al assessed the effects of lamotrigine on cognitive function. [1] The authors underlined the need to evaluate effects of lamotrigine on cognition in children taking monotherapy, especially with newly diagnosed epilepsy. Furthermore, they stress the need for longer-term studies comparing antiepileptic drugs which have demonstrated negative effects on cognitive neurodevelopment such as valproate. We believe that our preliminary results regarding cognitive abilities in children with newly diagnosed idiopathic generalized epilepsy during treatment with valporate and after switching to lamotrigine (active-control study) may give an additional perspective. [2] We would like further clarification on some aspects of the article. Cognition assessment variability is emphasized when evaluating complex data through clinically and genetically inhomogeneous population. Pressler et al presented results on 48 children with different epileptic syndromes of which 50% were children with symptomatic epilepsy. By this definition, there is less potential for therapeutic cognition alterations. It would be interesting to see results of cognitive outcome distributed by syndromes or by antiepileptic drug. To obtain greater reproducibility considering complex interchangeable data caution should be taken when interpreting with regard to coherence in genomics and genetics of sample (beyond heritance). [3] Another important issue is neuro-biology; developing brains need sufficient time to discriminate variation dynamics, (inter)test turnover times, translation of (in)coherent obtained results to both statistics and reality. In our group, average treatment on lamotrigine monotherapy was 10.3 months (minimum 6 months, maximum 22 months) and psychological assessments were performed after a minimum of 6 months upon switch from valproate to lamotrigine. [2] An add-on therapy’s effects are difficult to appraise, especially when exploring complexity of cognition. Currently, pharmacogenomics should not be disregarded. There are still unclear differences between lamotrigine and valproate profiles, at least considering P-glycoprotein. [4] According to our results, each child that switched from valproate to lamotrigine improved in attention, concentration, memory and ability for sequencing and processing. We confirmed that lamotrigine monotherapy treatment does not cause any impairment on specific cognitive functions in long-term follow-up of children with newly diagnosed epilepsy homogenous by epileptic syndrome and clinical variables. Both studies may impact clinical decisions of first antiepileptic drug choice especially in children with idiopathic generalized epilepsy. References 1. Pressler RM, Binnie CD, Coleshill SG, Chorley GA, Robinson RO. Effect of lamotrigine on cognition in children with epilepsy. Neurology 2006; 66:1495-1499. 2. Prpic I, Vlasic-Cicvaric I, Paucic-Kirincic E, Korotaj Z, Skarpa-Prpic I. Cognitive function improving in children with epilepsy switched from valproate to lamotrigine. Epilepsia 2002;43(suppl 8): 184. 3. R Ottman Analysis of Genetically Complex Epilepsies. Epilepsia. 2005 ; 46(Suppl 10): 7-14. 4. Weiss J, Kerpen CJ, Lindenmaier H, Dormann SMG, Haefeli WE. Interaction of Antiepileptic Drugs with Human P-Glycoprotein in Vitro. JPET 2003;307:262–267. Disclosure: The authors report no conflicts of interest.
Reply from the Authors 25 September 2006
Ronit M. Pressler, MD, National Hospital for Neurology and Neurosurgery Queen Square, London WC1N 3BG, UK, CD Binnie, RO Robinson Send Correspondence to journal: Re: Reply from the Authors ronit.pressler{at}uclh.nhs.uk Ronit M. Pressler, MD, et al.	Since the authors provide no data in the letter or the abstract cited, [2] it is difficult to comment on the significance of their results (the only form in which their study has to our knowledge been published is in the abstracts of the European Epilepsy Congress in 2002). Their results can only demonstrate the combined effects on cognition and behavior of sodium valproate withdrawal, starting lamotrigine, seizure reduction, possible suppression of interictal EEG discharges [5] and learning effects. Due to the large number of confounding factors and lack of control data it is difficult to attribute a change of cognition and behavior to lamotrigine. In contrast, we have avoided these confounding factors (and possible pharmacogenetic effects) by using a double blind, cross over placebo controlled study design and only including children with mild or well controlled epilepsy. [1] We do not know of any data suggesting that children with symptomatic epilepsy are more (or less) susceptible to the cognitive side effects of antiepileptic drugs. They may be at a higher risk for cognitive problems but in our study, the children act as their own controls and this should not influence the data. References 5. Pressler RM, Robinson RO, Wilson GA, Binnie CD. Treatment of interictal epileptiform discharges can improve behavior in children with behavioral problems and epilepsy. J Pediatr 2005 ;146:112-117. Disclosure: The authors report no conflicts of interest.