Perihan ÇAM RAY, Gonca Gül ÇELİK, Ayşegül YOLGA TAHİROĞLU, İpek SÜZER GAMLI, Özlem MİHRİBAN HERGÜNER

Methylphenidate treatment outcomes and gender differences in attentional deficit and hyperactivity disorder with epilepsy: a follow-up study

Objective: The aim of this study is to investigate the methylphenidate (MPH) treatment response in children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) with and without epilepsy. Methods: Ninety-four children and adolescents with ADHD consisting of 47 with and 47 without epilepsy were enrolled into the study. The patients were evaluated by DSM-IV-TR, the Stroop test, the Conners' Parent and Teacher Rating Scales. The groups were matched with regard to age, gender, ADHD subtype and comorbidity. The Stroop test was performed three times: during baseline (S-1); at the third month of the MPH treatment (S-2); after drug holiday of the treatment with MPH which lasted for six months (S-3). Stroop total time (ST) and Stroop total error+correction (SEC) scores were analyzed. Results: The mean ST-3 and SEC-3 scores were significantly higher in cases with ADHD-attention deficit (ADHD-AD) subtype with the epilepsy group compared to ADHD-combined type (ADHD-CT) in the epilepsy group, whereas there was no significant difference detected in the non-epilepsy groups. While in the boys with/ without epilepsy and the girls without epilepsy and were demonstrated significant reductions in all recorded ST and SEC scores during/after treatment in comparison with the initial scores, a similar relationship could not be shown for the girls with epilepsy. Conclusion: It is noted that gender and the ADHD subtypes may affect drug choice in patient with ADHD cases comorbid with epilepsy. One of the noticeable results of our study is was that the Stroop scores is no significant change with methylphenidate treatment in especially in girls with ADHD and epilepsy. (Anatolian Journal of Psychiatry 2019; 20(6):642-650)

Epilepsinin eşlik ettiği dikkat eksikliği hiperaktivite bozukluğunda metilfenidat tedavi yanıtı ve cinsiyet farklılıkları: İzleme çalışması

Amaç: Bu çalışmanın amacı, epilepsisi olan ve olmayan dikkat eksikliği hiperaktivite bozukluğu (DEHB) çocuk ve ergenlerde metilfenidat (MPH) tedavi yanıtının araştırmaktır. Yöntem: Çalışmaya, 47 epilepsili ve 47 epilepsisi olmayan DEHB’li 94 çocuk ve ergen alındı. Hastalar, DSM-IV-TR, Stroop testi, Conners Ebeveyn ve Öğretmen Değerlendirme Ölçeği ile değerlendirildi. Gruplar yaş, cinsiyet, DEHB alt tipi ve eş tanılar bakımından eşlendi. Stroop testi üç kez uygulandı: Başlangıçta (S-1), MPH tedavisinin üçüncü ayında (S-2), altı ay süren MPH ile tedavi- nin ilaç tatilinden sonra (S-3). Stroop toplam süre (SS) ve stroop toplam hata+düzeltme (SHD) puanları analiz edildi. Bulgular: Ortalama SS-3 ve SHD-3 puanları, epilepsisi olan DEHB-dikkat eksikliği (DEHB-DE) alt tipinde epilepsisi olan DEHB-birleşik tipine (DEHB-BT) göre anlamlı derecede daha yüksekti, fakat epilepsisi olmayanlarda DEHB alt tipleri arasında anlamlı farklılık gözlenmedi. Epilepsisi olan/olmayan erkeklerin ve epilepsisi olmayan kızlarda, başlangıç puanlarına göre tedavi sırasında/sonrasında kaydedilen tüm SS ve SHD puanlarında anlamlı düzeyde azalma gözlenirken, epilepsili kızlar için benzer bir ilişki gösterilememiştir. Sonuç: Cinsiyet ve DEHB alt tiplerinin, epilepsi ile birlikte olan DEHB olan hastalarda ilaç seçimini etkileyebileceği belirtilmektedir. Çalışmamızın dikkat çeken sonuçlarından biri, Stroop puanlarının, özellikle DEHB ve epilepsi olan kızlarda MPH tedavisi ile anlamlı bir değişiklik olmamasıdır. (Anadolu Psikiyatri Derg 2019; 20(6):642-650)

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Polanczyk G, De Lima MS, Horta BL, Biederman J, Rohde LA. The worldwide prevalence of ADHD: A systematic review and metaregression analysis. Am J Psychiatry 2007; 64:942-948.

Biederman J, Faraone SV. The Massachusetts General Hospital studies of gender influences on attention-deficit/hyperactivity disorder in youth and relatives. Psychiatr Clin North Am 2004; 27:225-232.

Skounti M, Philalithis A, Galanakis E, Variations in prevalence of attention deficit hyperactivity disor- der worldwide. Eur J Pediatr 2007; 166:117-123.

Turky A, Beavis JM, Thapar AK, Kerr MP. Psycho- pathology in children and adolescents with epi- lepsy: an investigation of predictive variables. Epilepsy Behav 2008; 12:136-144.

Pellock JM. Understanding co-morbidities af-fecting children with epilepsy. Neurology 2004; 62:17-23.

Dunn DW. Should pediatric neurologists play a role in the management of the most common psychiatric comorbidities in children with epilep-sy? Practical considerations. Epilepsy Behav 2018; doi: 10.1016/j.yebeh.2018.11.013.

Kaufmann R, Goldberg-Stern H, Shuper A. Atten-tion-deficit disorders and epilepsy in childhood: incidence, causative relations and treatment possibilities. J Child Neurol 2009; 24:727-733.

Russ SA, Larson K, Halfton N. A national profile of childhood epilepsy and seizure disorder. Pediatrics 2012; 129:256-264.

Cohen R, Senecky Y, Shuper A, Inbar D, Chodick G, Shalev V, et al. Prevalence of epilepsy and attention- deficit hyperactivity (ADHD) disorder: A population-based study. J Child Neurol 2013; 28(1):120-123.

Reilly CJ, Atkinson P, Das KB, Chin RF, Aylett SE, Burch V, et al. Neurobehavioral comorbidities in children with active epilepsy: A population- based study. Pediatrics 2014; 133:1586-1593.

Liu X, Carney PR, Bussing R, Segal R, Cottler LB, Winterstein AG. Stimulants do not increase the risk of seizure-related hospitalizations in children with epilepsy. J Child Adolesc Psychopharmacol 2018; 28(2):111-116.

Hesdorffer DC, Ludvigsson P, Olafsson E, Gud-mundsson G, Kjartansson O, Hauser WA. ADHD as a risk factor for incident unprovoked seizures and epilepsy in children. Arch Gen Psychiatry 2004; 61:731-736.

Davis SM, Katusic SK, Barbaresi WJ, Killian J, Weaver AL, Ottman R, et al. Epilepsy in children with attention-deficit/hyperactivity disorder. Pedi-atr Neurol 2010; 42:325-330.

Weinshenker D, Szot P. The role of catechola-mines in seizure susceptibility. New results using genetically engineered mice. Pharmacol Ther 2002; 94:213-233.

Gücüyener K, Erdemoğlu AK, Şenol S, Serda-roglu A, Soysal S, Kockar AI. Use of methylpheni-date for attention-deficit hyperactivity disorder in patients with epilepsy or electroencephalographic abnormalities. J Child Neurol 2003; 18:109-112.

Radziuk AL, Kieling RR, Santos K, Rotert R, Bastos F, Palmini AL. Methylphenidate improves the quality of life of children and adolescents with ADHD and difficult-to-treat epilepsies. Epilepsy Behav 2015; 46:215-220.

Socanski D, Aurlien D, Herigstad A, Thomsen PH, Larsen TK. Attention deficit/hyperactivity disorder and interictal epileptiform discharges: it is safe to use methylphenidate? Seizure 2015; 25:80-83.

Rheims S, Herbillon V, Villeneuve N, Auvin S, Napuri S, Cances C, et al. Investigators of the Paediatric Epilepsy REsearch NeEwork (PERENE). ADHD in childhood epilepsy: Clinical determinants of severity and of the response to methylphenidate. Epilepsia 2016; 57(7):1069-1077.

Kral MC, Lally MD, Boan AD. Effectiveness and side effect profile of stimulant medication for the treatment of attention-deficit/hyperactivity disor-der in youth with epilepsy. J Child Adolesc Psychopharmacol 2017; 27(8):735-740.

Gonzalez-Heydrich J, Whitney J, Waber D, Forbes P, Hsin O, Faraone SV, et al. Adaptive phase I study of OROS methylphenidate treat-ment of attention deficit hyperactivity disorder with epilepsy. Epilepsy Behav 2010; 18: 229-237.

Fosi T, Lax-Pericall MT, Scott RC, Neville BGR, Aylett SE. Methylphenidate treatment of attention deficit hyperactivity disorder in young people with learning disability and difficult-to-treat epilepsy: Evidence of clinical benefit. Epilepsia 2013; 54:2071-2081.

Santos K, Palmini A, Radziuk AL, Rotert R, Bastos F, Booij L, et al. The impact of methylphenidate on seizure frequency and severity in children with attention-deficit-hyperactivity disorder and diffi-cult-to-treat epilepsies. Dev Med Child Neurol 2013; 55(7):654-660.

Ravi M, Ickowicz A. Epilepsy, attention-deficit/ hyperactivity disorder and methylphenidate: criti-cal examination of guiding evidence. J Can Acad Child Adolesc Psychiatry. 2016; 25(1):50-58.

Park J, Choi HW, Yum MS, Ko TS, Shon SH, Kim HW. Relationship between aggravation of sei-zures and methylphenidate treatment in subjects with attention-deficit/hyperactivity disorder and epilepsy. J Child Adolesc Psychopharmacol 2018; 28(8):537-546.

American Psychiatric Association. Diagnostic and Statistical Manual for Mental Disorders (DSM-IV), Fourth ed. Washington, DC: American Psychiatric Association, 1994.

Stroop JR. Studies of interference in serial verbal reactions. J Experimental Psychol 1935; 18:643-662.

Karakaş S, Erdogan E, Sak L, Soysal AŞ, Ulusoy T, Ulusoy İY, ve ark. Stroop testi TBAG formu: Türk kültürüne standardizasyon çalışması, güve-nirlik ve geçerlilik. Klinik Psikiyatri 1999; 2:75-88.

Kılıç BG, Koçkar AI, Irak M, Şener Ş, Karakaş S. Stroop testi TBAG formunun 6-11 yaş grubu çocuklarda standardizasyon çalışması. Çocuk ve Gençlik Ruh Sağlığı Dergisi 2002; 9:86-99.

Conners CK. Rating scales for use in drug studies with children. Psychopharm Bull (Special Issue-pharmacotherapy with children) 1973; 24-84.

Sener S, Dereboy Ç, Dereboy IF. Conners öğret-men derecelendirme ölçeği Türkçe uyarlaması-I. Çocuk ve Gençlik Ruh Sağlığı Dergisi 1995; 2:131-141.

Dereboy Ç, Şenol S, Şener Ş. Conners anababa derecelendirme ölçeği uyarlama çalışması. X. Ulusal Psikoloji Kongresi, Ankara, 1998, s.42.

Ayaz M, Karakaya I, Ayaz AB, Kara B, Kutlu M. Psychiatric and neurocognitive evaluation fo-cused on frontal lobe functions in rolandic epi-lepsy. NöroPsikiyatri Arşivi 2013; 50:209-215.

Barkley RA. The inattentive type of ADHD as a distinct disorder: What remains to be done. Clin Psychol-Sci PR 2001; 8:489-493.

Roessner V, Sagvolden T, Dasbanerjee T, Mid-dleton FA, Faraone SV, Walaas SI, et al. Methyl-phenidate normalizes elevated dopamine trans-porter densities in an animal model of the atten-tion-deficit/hyperactivity disorder combined type, but not to the same extent in one of the attention-deficit/hyperactivity disorder inattentive type. Neuroscience 2010; 167:1183-1191.

Loutfi KS, Carvalho AM, Lamounier JA, Nasci-mento Jde A. ADHD and epilepsy: contributions from the use of behavioral rating scales to inves-tigate psychiatric comorbidities. Epilepsy Behav 2011; 20:484-489.

Dunn DW, Austin JK, Harezlak J, Ambrosius WT. ADHD and epilepsy in childhood. Dev Med Child Neurol 2003; 45(1):50-54.

Socanski D, Aurlien D, Herigstad A, Thomsen PH, Larsen TK. Epilepsy in a large cohort of children diagnosed with attention deficit/hyperactivity disorders (ADHD). Seizure 2013; 22(8):651-655.

Plioplys S, Dunn DW, Caplan R. 10-year research update review: psychiatric problems in children with epilepsy. J Am Acad Child Adolesc Psychiatry 2007; 46:1389-1402.

Gonzalez-Heydrich J, Dodds A, Whitney J, Mac-Millan C, Waber D, Faraone SV, et al. Psychiatric disorders and behavioral characteristics of pediat-ric patients with both epilepsy and attention-deficit hyperactivity disorder. Epilepsy Behav 2007; 10:384-388.

Verrotti A, Moavero R, Panzarino G, Di Paolan-tonio C, Rizzo R, Curatolo P. The challenge of pharmacotherapy in children and adolescents with epilepsy-ADHD comorbidity. Clin Drug Investig 2018; 38(1):1-8.

Williams AE, Giust JM, Kronenberger WG, Dunn DW. Epilepsy and attention-deficit hyperactivity disorder: Links, risks, and challenges. Neuro-psychiatr Dis Treat 2016; 12:287-296.

Zhou W, Cunningham KA, Thomas ML. Estrogen regulation of gene expression in the brain: a possible mechanism altering the response to psychostimulants in female rats. Brain Res Mol Brain 2002; 100:75-83.

Freese L, Muller EJ, Souza MF, Couto-Pereira NS, Tosca CF, Ferigolo M, Barros HM, et al. GABA system changes in methylphenidate sen-sitized female rats. Behav Brain Res 2012; 231:181-186.

Wagner AK, Kline AE, Ren D, Willard LA, Wenger MK, Zafonte RD. Gender associations with chron-ic methylphenidate treatment and behavioral performance following experimental traumatic brain injury. Behav Brain Res 2007; 181:200-209.

Brown RW, Hughes BA, Hughes AB, Sheppard AB, Perna MK, Ragsdale WL, et al. Sex and dose-related differences in methylphenidate adolescent locomotor sensitization and effects on brain-derived neurotrophic factor. J Psychopharmacol 2012; 26:1480-1488.