药学学报, 2018, 53(3): 321-327
引用本文:
徐祥清, 王克威. 孤独症谱系障碍的药物治疗研究进展[J]. 药学学报, 2018, 53(3): 321-327.
XU Xiang-qing, WANG Ke-wei. Research progress in medicinal treatment of autism spectrum disorders [J]. Acta Pharmaceutica Sinica, 2018, 53(3): 321-327.

孤独症谱系障碍的药物治疗研究进展
徐祥清1, 王克威2
1. 江苏恩华药业股份有限公司, 江苏 徐州 221116;
2. 青岛大学药学院, 山东 青岛 266021
摘要:
孤独症谱系障碍(autistic spectrum disorder,ASD)是一组严重影响儿童健康、具有显著临床和病因异质性的中枢神经系统发育障碍性疾病,表现为社会互作障碍、语言障碍及多种类型的重复性行为,其病因及发病机制均尚未完全阐明,迄今为止尚无特异性的治疗药物。目前,对ASD多采用行为干预为主而药物治疗为辅的综合性治疗措施。行为干预对ASD的核心症状有一定的治疗效果,药物治疗对核心症状效果虽然不大,但对其他的症状如易激惹、攻击性、自残行为、焦虑、高活动性、失眠、强迫行为及注意力不集中等具有一定的改善作用。目前有较多的药物正在进行ASD的临床及临床前实验研究,这些药物包括第二代抗精神病药、抗抑郁药、抗多动症药物、抗癫痫药、抗感染药、谷氨酸受体调节剂、GABA受体调节剂、mTOR抑制剂和神经肽类等。本文将对治疗ASD药物的临床及临床前研究进展进行综述。
关键词:    孤独症谱系障碍      药物治疗      抗精神病药      抗抑郁药      阿立哌唑      利培酮     
Research progress in medicinal treatment of autism spectrum disorders
XU Xiang-qing1, WANG Ke-wei2
1. Jiangsu Nhwa Pharmaceutical Co., Ltd., Xuzhou 221116, China;
2. School of Pharmacy, Qingdao University, Qingdao 266021, China
Abstract:
Autism spectrum disorders (ASD) are a group of behaviorally defined, etiologically heterogeneous neurodevelopmental disorders characterized by impairment in social reciprocity, disturbances in language and various types of repetitive behaviors. The etiology and pathogenic mechanism of ASD are still unclear and there is no effective treatment available yet. ASD treatment includes behavioral and medicinal interventions. Behavioral interventions are the first line of treatment for ASD, alleviating core symptoms. Medicinal treatments, exert limited effect towards the core symptoms, represent an aide to the behavioral intervention and mainly apply to the so-called associated behavioral symptoms, such as irritability, aggression, self-injury, anxiety, insomnia, hyperactivity, low attention and compulsive behavior. A wide range of different agents are currently being tested in the preclinical and clinical studies, which include antipsychotics, antidepressants, anticonvulsants, anxiolytics, anti-infective drugs, glutamate receptor modulators, GABA receptor modulators, mTOR inhibitors and neuropeptides, etc. The purpose of present review is to cover the research advances in drug development and medicinal treatment of autism spectrum disorders.
Key words:    autism spectrum disorders    drug therapy    antipsychotic    antidepressant    aripiprazole    risperidone   
收稿日期: 2017-09-13
DOI: 10.16438/j.0513-4870.2017-0912
通讯作者: 王克威,Tel/Fax:86-532-82991070,E-mail:wangkw@qdu.edu.cn
Email: wangkw@qdu.edu.cn
相关功能
PDF(207KB) Free
打印本文
0
作者相关文章
徐祥清  在本刊中的所有文章
王克威  在本刊中的所有文章

参考文献:
[1] Lai MC, Lombardo MV, Baron-Cohen S. Autism[J]. Lancet, 2014, 383:896-910.
[2] McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems[J]. N Engl J Med, 2002, 347:314-321.
[3] Canitano R, Scandurra V. Psychopharmacology in autism:an update[J]. Prog Neuropsychopharmacol Biol Psychiatry, 2011, 35:18-28.
[4] Ghanizadeh A, Sahraeizadeh A, Berk M. A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial[J]. Child Psychiatry Hum Dev, 2014, 45:185-192.
[5] Wink LK, Early M, Schaefer T, et al. Body mass index change in autism spectrum disorders:comparison of treatment with risperidone and aripiprazole[J]. J Child Adolesc Psychopharmacol, 2014, 24:78-82.
[6] Boon-yasidhi V, Jearnarongrit P, Tulayapichitchock P, et al. Adverse effects of risperidone in children with autism spectrum disorders in a naturalistic clinical setting at Siriraj Hospital, Thailand[J]. Psychiatry J, 2014, 2014:136158.
[7] Hongkaew Y, Ngamsamut N, Puangpetch A, et al. Hyper­prolactinemia in Thai children and adolescents with autism spectrum disorder treated with risperidone[J]. Neuropsy­chiatr Dis Treat, 2015, 11:191.
[8] Levine SZ, Kodesh A, Goldberg Y, et al. Initial severity and efficacy of risperidone in autism:results from the RUPP trial[J]. Eur Psychiatry, 2016, 32:16-20.
[9] Kent JM, Kushner S, Ning X, et al. Risperidone dosing in children and adolescents with autistic disorder:a double-blind, placebo-controlled study[J]. J Autism Dev Disord, 2013, 43:1773-1783.
[10] Aman M, Rettiganti M, Nagaraja HN, et al. Tolerability, safety, and benefits of risperidone in children and adolescents with autism:21-month follow-up after 8-week placebo-controlled trial[J]. J Child Adolesc Psychopharmacol, 2015, 25:482- 493.
[11] Ghaeli P, Nikvarz N, Alaghband-Rad J, et al. Effects of risperidone on core symptoms of autistic disorder based on childhood autism rating scale:an open label study[J]. Indian J Psychol Med, 2014, 36:66.
[12] Marcus RN, Owen R, Manos G, et al. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder:a 52-week, open-label, multicenter study[J]. J Clin Psychiatry, 2011, 72:1270-1276.
[13] Ichikawa H, Mikami K, Okada T, et al. Aripiprazole in the treatment of irritability in children and adolescents with autism spectrum disorder in Japan:a randomized, double-blind, placebo-controlled study[J]. Child Psychiatry Hum Dev, 2016. DOI:10.1007/s10578-016-0704-x.
[14] Maloney A, Mick EO, Frazier J. Aripiprazole decreases irritability in 12 out of 14 youth with autism spectrum disor­ders[J]. J Child Adolesc Psychopharmacol, 2014, 24:357-359.
[15] Xie Q, Tang J, Xu Y, et al. Clinical observation of aripiprazole in the treatment of autism[J]. Chin J Contemp Pediatr (中国当代儿科杂志), 2013, 15:294-297.
[16] Stachnik JM, Nunn-Thompson C. Use of atypical antipsy­chotics in the treatment of autistic disorder[J]. Ann Phar­macother, 2007, 41:626-634.
[17] Loebel A, Brams M, Goldman RS, et al. Lurasidone for the treatment of irritability associated with autistic disorder[J]. J Autism Dev Disord, 2016, 46:1153-1163.
[18] Golubchik P, Sever J, Weizman A. Low-dose quetiapine for adolescents with autistic spectrum disorder and aggressive behavior:open-label trial[J]. Clin Neuropharmacol, 2011, 34:216-219.
[19] Malone RP, Delaney MA, Hyman SB, et al. Ziprasidone in adolescents with autism:an open-label pilot study[J]. J Child Adolesc Psychopharmacol, 2007, 17:779-790.
[20] McDougle CJ, Kem DL, Posey DJ. Case series:use of ziprasidone for maladaptive symptoms in youths with autism[J]. J Am Acad Child Adolesc Psychiatry, 2002, 41:921-927.
[21] Hollander E, Wasserman S, Swanson EN, et al. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder[J]. J Child Adolesc Psychopharmacol, 2006, 16:541-548.
[22] Kemner C, Willemsen-Swinkels S, De Jonge M, et al. Open-label study of olanzapine in children with pervasive developmental disorder[J]. J Clin Psychopharmacol, 2002, 22:455-460.
[23] Fido A, Al-Saad S. Olanzapine in the treatment of behavioral problems associated with autism:an open-label trial in Kuwait[J]. Med Princ Pract, 2008, 17:415-418.
[24] McPheeters ML, Warren Z, Sathe N, et al. A systematic review of medical treatments for children with autism spectrum disorders[J]. Pediatrics, 2011, 127:e1312-e1321.
[25] Owley T, Walton L, Salt J, et al. An open-label trial of escitalopram in pervasive developmental disorders[J]. J Am Acad Child Adolesc Psychiatry, 2005, 44:343-348.
[26] Hollander E, Kaplan A, Cartwright C, et al. Venlafaxine in children, adolescents, and young adults with autism spectrum disorders:an open retrospective clinical report[J]. J Child Neurol, 2000, 15:132-135.
[27] Posey DJ, Guenin KD, Kohn AE, et al. A naturalistic open-label study of mirtazapine in autistic and other pervasive developmental disorders[J]. J Child Adolesc Psychopharmacol, 2001, 11:267-277.
[28] Hollander E, Phillips A, Chaplin W, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism[J]. Neuropsychopharma­cology, 2005, 30:582.
[29] King BH, Hollander E, Sikich L, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior:citalopram ineffective in children with autism[J]. Arch Gen Psychiatry, 2009, 66:583-590.
[30] Martin A, Koenig K, Anderson GM, et al. Low-dose fluvoxamine treatment of children and adolescents with pervasive developmental disorders:a prospective, open-label study[J]. J Autism Dev Disord, 2003, 33:77-85.
[31] Sanchez LE, Campbell M, Small AM, et al. A pilot study of clomipramine in young autistic children[J]. J Am Acad Child Adolesc Psychiatry, 1996, 35:537-544.
[32] Domes G, Heinrichs M, Gläscher J, et al. Oxytocin attenuates amygdala responses to emotional faces regardless of valence[J]. Biol Psychiatry, 2007, 62:1187-1190.
[33] Anagnostou E, Soorya L, Brian J, et al. Intranasal oxytocin in the treatment of autism spectrum disorders:a review of literature and early safety and efficacy data in youth[J]. Brain Res, 2014, 1580:188-198.
[34] Chez MG, Burton Q, Dowling T, et al. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders:an observation of initial clinical response and maintenance tolerability[J]. J Child Neurol, 2007, 22:574- 579.
[35] Xu CJ. Advances in medicine and supplementary treatment of autism spectrum disorders[J]. Chin Comm Doc (中国社区医师), 2014, 30:10-11.
[36] Chez MG, Aimonovitch M, Buchanan T, et al. Treating autistic spectrum disorders in children:utility of the cholinesterase inhibitor rivastigmine tartrate[J]. J Child Neurol, 2004, 19:165-169.
[37] Hardan AY, Handen BL. A retrospective open trial of adjunctive donepezil in children and adolescents with autistic disorder[J]. J Child Adolesc Psychopharmacol, 2002, 12:237-241.
[38] Nicolson R, Craven-Thuss B, Smith J. A prospective, open-label trial of galantamine in autistic disorder[J]. J Child Adolesc Psychopharmacol, 2006, 16:621-629.
[39] Ming X, Gordon E, Kang N, et al. Use of clonidine in children with autism spectrum disorders[J]. Brain Dev, 2008, 30:454-460.
[40] Eichaar GM, Maisch NM, Augusto LM, et al. Pediatrics efficacy and safety of naltrexone use in pediatric patients with autistic disorder[J]. Ann Pharmacother, 2006, 40:1086- 1095.
[41] Wirojanan J, Jacquemont S, Diaz R, et al. The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome[J]. J Clin Sleep Med, 2009, 5:145-150.
[42] Cannell JJ. On the aetiology of autism[J]. Acta Paediatr, 2010, 99:1128-1130.
[43] Al-Amin MM, Rahman MM, Khan FR, et al. Astaxanthin improves behavioral disorder and oxidative stress in prenatal valproic acid-induced mice model of autism[J]. Behav Brain Res, 2015, 286:112-121.
[44] Bambini-Junior V, Zanatta G, Nunes GDF, et al. Resveratrol prevents social deficits in animal model of autism induced by valproic acid[J]. Neurosci Lett, 2014, 583:176-181.
[45] Li G, Han WJ, Jin J, et al. Design, synthesis and biological evaluation of fingolimod analogues containing diphenyl ether moiety[J]. Acta Pharm Sin (药学学报), 2014, 49:896-904.
[46] Wu H, Wang X, Gao J, et al. Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism[J]. Life Sci, 2017, 173:43-54.
[47] Kumar H, Sharma B. Minocycline ameliorates prenatal valproic acid induced autistic behaviour, biochemistry and blood brain barrier impairments in rats[J]. Brain Res, 2016, 1630:83-97.
[48] Wang CC, Lin HC, Chan YH, et al. 5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model[J]. Int J Neuropsychopharmacol, 2013, 16:2027-2039.
[49] Naviaux RK, Zolkipli Z, Wang L, et al. Antipurinergic therapy corrects the autism-like features in the poly (IC) mouse model[J]. PLoS One, 2013, 8:e57380.
[50] Baronio D, Castro K, Gonchoroski T, et al. Effects of an H3R antagonist on the animal model of autism induced by prenatal exposure to valproic acid[J]. PLoS One, 2015, 10:e0116363.
[51] Silverman JL, Pride MC, Hayes JE, et al. GABAB receptor agonist R-baclofen reverses social deficits and reduces repetitive behavior in two mouse models of autism[J]. Neuropsycho­pharmacology, 2015, 40:2228-2239.
[52] Aguilar-Valles A, Matta-Camacho E, Khoutorsky A, et al. Inhibition of group I metabotropic glutamate receptors reverses autistic-like phenotypes caused by deficiency of the translation repressor eIF4E binding protein 2[J]. J Neurosci, 2015, 35:11125-11132.
[53] Mehta MV, Gandal MJ, Siegel SJ. mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism[J]. PLoS One, 2011, 6:e26077.