Pharmacogenetic impact on the methylphenidate-hydrocloride treatment in children with attention-deficit hyperactivity disorder

doi:10.11852/zgetbjzz2023-0489

Abstract

Abstract: Attention-deficit hyperactivity disorder (ADHD) is one of the most common chronic neurodevelopmental disorders in childhood.It is mainly manifested as inattention, hyperactivity, and impulsivity that are inconsistent with the development level, which may lead to multiple functional impairments and place heavy burdens on individuals, families, and society.Methylphenidate hydrochloride (MPH) is a first-line treatment drug for ADHD, which is widely used in clinical practice.However, some patients have no response to drug treatment and adverse reactions often cause premature termination of treatment.Introducing the concept of pharmacogenetics into MPH treatment may open new avenues for individualized interventions of ADHD.This paper aims to review the impact of pharmacogenetics on MPH treatment in children with ADHD and to provide references for clinical drug treatment and management.

Key words: attention-deficit hyperactivity disorder, pharmacogenetics, methylphenidate-hydrocloride, pharmacokinetics, pharmacodynamics

摘要： 注意缺陷多动障碍(ADHD)是儿童期最常见的慢性神经发育障碍之一,以与发育水平不匹配的注意力不集中、多动冲动为主要表现,可能导致多种功能损害,给个人、家庭、社会带来沉重负担。盐酸哌甲酯(MPH)是一种ADHD一线治疗药物,临床应用广泛,但部分患者对药物治疗无反应、出现不良反应等原因过早终止治疗。在治疗中引入药物遗传学的概念可能为 ADHD的个体化干预开辟新的途径。本文旨在综述药物遗传学对ADHD儿童MPH治疗的影响,为临床药物治疗及管理提供参考。

关键词: 注意缺陷多动障碍, 药物遗传学, 盐酸哌甲酯, 药代动力学, 药效动力学

CLC Number:

R749.94

REN Miaomiao, CHEN Li. Pharmacogenetic impact on the methylphenidate-hydrocloride treatment in children with attention-deficit hyperactivity disorder[J]. Chinese Journal of Child Health Care, 2024, 32(3): 296-300.

任苗苗, 陈立. 药物遗传学对注意缺陷多动障碍儿童盐酸哌甲酯治疗的影响[J]. 中国儿童保健杂志, 2024, 32(3): 296-300.

References

[1] 中华医学会儿科学分会发育行为学组.注意缺陷多动障碍早期识别、规范诊断和治疗的儿科专家共识[J].中华儿科杂志, 2020, 58(3):188-193.
The Subspecialty Group of Developmental and Behavioral Pediatrics, the Society of Pediatrics, Chinese Medical Association.Consensus on pediatric clinical practice of early identification, standardized diagnosis and treatment of attention deficit hyperactivity disorder[J].Chin J Pediatr, 2020, 58(3):188-193.(in Chinese)
[2] Posner J, Polanczyk G V, Sonuga-Barke E.Attention-deficit hyperactivity disorder[J].Lancet, 2020, 395(10222):450-462.
[3] Wang T, Liu K, Li Z, et al.Prevalence of attention deficit/hyperactivity disorder among children and adolescents in China: A systematic review and meta-analysis[J].BMC Psychiatry, 2017, 17(1):32.
[4] Thomas R, Sanders S, Doust J, et al.Prevalence of attention-deficit/hyperactivity disorder: A systematic review and Meta-analysis[J].Pediatrics, 2015, 135(4):e994-e1001.
[5] Raman SR, Man KKC, Bahmanyar S, et al.Trends in attention-deficit hyperactivity disorder medication use: A retrospective observational study using population-based databases[J].Lancet Psychiatry, 2018, 5(10):824-835.
[6] Johnston BA, Coghill D, Matthews K, et al.Predicting methylphenidate response in attention deficit hyperactivity disorder: A preliminary study[J].J Psychopharmacol, 2015, 29(1):24-30.
[7] Faraone SV.Molecular genetics of attention deficit hyperactivity disorder[J].Psychiatr Clin North Am, 2010, 33(1):159-180.
[8] Wenthur CJ.Classics in chemical neuroscience: Methylphenidate[J].ACS Chem Neurosci, 2016, 7(8):1030-1040.
[9] Steingard R, Taskiran S, Connor DF, et al.New formulations of stimulants: An update for clinicians[J].J Child Adolesc Psychopharmacol, 2019, 29(5):324-339.
[10] Markowitz JS, Melchert PW.The pharmacokinetics and pharmacogenomics of psychostimulants[J].Child Adolesc Psychiatr Clin N Am, 2022, 31(3):393-416.
[11] Zhu HJ, Patrick KS, Yuan HJ, et al.Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in Man: Clinical significance and molecular basis[J].Am J Hum Genet, 2008, 82(6):1241-1248.
[12] Merali Z, Ross S, Paré G.The pharmacogenetics of carboxylesterases: CES1 and CES2 genetic variants and their clinical effect[J].Drug Metabol Drug Interact, 2014, 29(3).
[13] Stage C, Jürgens G, Guski L S, et al.The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects: Impact of CES1 genotype on methylphenidate pharmacokinetics[J].Br J Clin Pharmacol, 2017, 83(7):1506-1514.
[14] Stage C, Dalhoff K, Rasmussen HB, et al.The impact of human CES1 genetic variation on enzyme activity assessed by ritalinic acid/methylphenidate ratios[J].Basic Clin Pharmacol Toxicol, 2019, 125(1):54-61.
[15] Lyauk Y, Stage C, Bergmann T, et al.Population pharmacokinetics of methylphenidate in healthy adults emphasizing novel and known effects of several carboxylesterase 1 (CES1) Variants[J].Clin Transl Sci, 2016, 9(6):337-345.
[16] Newcorn J.Carboxylesterase 1 Genetic Variation and Methylphenidate in ADHD[EB/OL].(2018-12-20)[2023-01-10].https://clinicaltrials.gov/.
[17] Nemoda Z, Angyal N, Tarnok Z, et al.Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD[J].Neuropharmacology, 2009, 57(7-8):731-733.
[18] Stevens T, Sangkuhl K, Brown J T, et al.PharmGKB summary: Methylphenidate pathway, pharmacokinetics/pharmacodynamics[J].Pharmacogenet Genomics, 2019, 29(6):136-154.
[19] Brown JT, Beery N, Taran A, et al.Associations between CES1 variants and dosing and adverse effects in children taking methylphenidate[J].Front Pediatr, 2023, 10: 958622.
[20] Zhu HJ, Appel DI, Peterson YK, et al.Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: Potential sources of metabolic drug interactions[J].Toxicology, 2010, 270(2-3):59-65.
[21] Faraone SV, Larsson H.Genetics of attention deficit hyperactivity disorder[J].Mol Psychiatry, 2019, 24(4):562-575.
[22] Akutagava-Martins GC, Rohde LA, Hutz MH.Genetics of attention-deficit/hyperactivity disorder: An update[J].Expert Rev Neurother, 2016, 16(2):145-156.
[23] Quintero J, Gutiérrez-Casares JR, Álamo C.Molecular characterisation of the mechanism of action of stimulant drugs lisdexamfetamine and methylphenidate on ADHD neurobiology: A review[J].Neurol Ther, 2022, 11(4):1489-1517.
[24] Cortese S.Pharmacologic treatment of attention deficit-hyperactivity disorder[J].N Engl J Med, 2020, 383(11):1050-1056.
[25] Faraone SV.The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities[J].Neurosci Biobehav Rev, 2018, 87: 255-270.
[26] Grünblatt E, Werling AM, Roth A, et al.Association study and a systematic meta-analysis of the VNTR polymorphism in the 3'-UTR of dopamine transporter gene and attention-deficit hyperactivity disorder[J].J Neural Transm (Vienna), 2019, 126(4):517-529.
[27] Soleimani R, Salehi Z, Soltanipour S, et al.SLC6A3 polymorphism and response to methylphenidate in children with ADHD: A systematic review and meta-analysis[J].Am J Med Genet B Neuropsychiatr Genet, 2018, 177(3):287-300.
[28] Kambeitz J, Romanos M, Ettinger U.Meta-analysis of the association between dopamine transporter genotype and response to methylphenidate treatment in ADHD[J].Pharmacogenomics J, 2014, 14(1):77-84.
[29] Hong SB, Kim JW, Cho SC, et al.Dopaminergic and noradrenergic gene polymorphisms and response to methylphenidate in Korean children with attention-deficit/hyperactivity disorder: Is there an interaction?[J].J Child Adolesc Psychopharmacol, 2012, 22(5):343-352.
[30] Pappa I, Mileva-Seitz VR, Bakermans-Kranenburg MJ, et al.The magnificent seven: A quantitative review of dopamine receptor d4 and its association with child behavior[J].Neurosci Biobehav Rev, 2015, 57: 175-186.
[31] Myer NM, Boland J R, Faraone SV.Pharmacogenetics predictors of methylphenidate efficacy in childhood ADHD[J].Mol Psychiatry, 2018, 23(9):1929-1936.
[32] Bonvicini C, Cortese S, Maj C, et al.DRD4 48 bp multiallelic variants as age-population-specific biomarkers in attention-deficit/hyperactivity disorder[J].Transl Psychiatry, 2020, 10(1):70.
[33] Naumova D, Grizenko N, Sengupta SM, et al.DRD4 exon 3 genotype and ADHD: Randomised pharmacodynamic investigation of treatment response to methylphenidate[J].World J Biol Psychiatry, 2019, 20(6):486-495.
[34] Lario S, Calls J, Cases A, et al.MspI identifies a biallelic polymorphism in the promoter region of the alpha 2A-adrenergic receptor gene[J].Clin Genet, 1997, 51(2):129-130.
[35] Froehlich TE, Epstein JN, Nick TG, et al.Pharmacogenetic predictors of methylphenidate dose-response in attention-deficit/hyperactivity disorder[J].J Am Acad Child Adolesc Psychiatry, 2011, 50(11):1129-1139.e2.
[36] Yuan D, Zhang M, Huang Y, et al.Noradrenergic genes polymorphisms and response to methylphenidate in children with ADHD: A systematic review and meta-analysis[J].Medicine (Baltimore), 2021, 100(46):e27858.
[37] Gomez-Sanchez CI, Carballo JJ, Riveiro-Alvarez R, et al.Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: Long-term effects[J].Sci Rep, 2017, 7(1):10391.
[38] Kim BN, Cummins TDR, Kim JW, et al.Val/Val genotype of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with a better response to OROS-MPH in Korean ADHD children[J].Int J Neuropsychopharmacol, 2011, 14(10):1399-1410.
[39] Park S, Kim JW, Kim BN, et al.No significant association between the alpha-2a-adrenergic receptor gene and treatment response in combined or inattentive subtypes of attention-deficit hyperactivity disorder[J].Pharmacopsychiatry, 2013, 46(5):169-174.
[40] Sun H, Yuan F, Shen X, et al.Role of COMT in ADHD: A systematic meta-analysis[J].Mol Neurobiol, 2014, 49(1):251-261.
[41] 陈敏, 陈芸, 汤宜朗, 等.单胺氧化酶A基因单体型预测注意缺陷多动障碍哌甲酯治疗的反应[J].中国心理卫生杂志, 2014, 28(10):748-753.
Chen M, Chen Y, Tang YL, et al.Association of better methylphenidate response with a haplotype of monoamine oxidase A gene in the treatment of attention-deficit/hyperactivity disorder[J].Chin Ment Health J, 2014, 28(10):748-753.(in Chinese)
[42] Angyal N, Horvath EZ, Tarnok Z, et al.Association analysis of norepinephrine transporter polymorphisms and methylphenidate response in ADHD patients[J].Prog Neuropsychopharmacol Biol Psychiatry, 2018, 84: 122-128.
[43] 丁凯景, 丁雨钦, 刘艳, 等.GRIN2A、GRIN2B基因多态性与哌甲酯治疗注意缺陷多动障碍疗效的关系研究[J].浙江医学, 2022, 44(19):2064-2069.
Ding KJ, Ding YQ, Liu Y, et al.Association of GRIN2A, GRIN2B gene polymorphisms and the efficacy of methylphenidate in treatment of attention deficit hyperactivity disorder[J].Zhejiang Med, 2022, 44(19):2064-2069.(in Chinese)