Osland Sydney T, Steeves Thomas Dl, Pringsheim Tamara
Department of Pediatrics, University of Calgary, 3280 Hospital Dr NW, Calgary, Alberta, Canada, T0L0X0.
Cochrane Database Syst Rev. 2018 Jun 26;6(6):CD007990. doi: 10.1002/14651858.CD007990.pub3.
This is an update of the original Cochrane Review published in Issue 4, 2011.Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non-stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. OBJECTIVES: To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics.
In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies.
We included randomized, double-blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel-group and cross-over study designs.
We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach.
We included eight randomized controlled trials (four of which were cross-over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta-analysis due to important clinical heterogeneity and unit-of-analysis issues.Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low-quality evidence for methylphenidate, atomoxetine, and clonidine, and very low-quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High-dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine.
AUTHORS' CONCLUSIONS: Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed.Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population.
这是对2011年第4期发表的原始Cochrane系统评价的更新。注意缺陷多动障碍（ADHD）是使抽动障碍复杂化的共病精神障碍中最常见的一种。常用于治疗ADHD症状的药物包括兴奋剂，如哌甲酯和苯丙胺；非兴奋剂，如托莫西汀；三环类抗抑郁药；以及α-激动剂。α-激动剂也用于治疗抽动。由于ADHD症状对抽动障碍儿童的影响，ADHD的治疗通常比抽动的药物管理更为重要。然而，几十年来，临床医生一直不愿使用兴奋剂治疗患有ADHD和抽动的儿童，因为担心会加重他们的抽动症状。
评估药物治疗对患有共病抽动障碍的儿童ADHD症状及抽动症状的影响。
2017年9月，我们检索了Cochrane中心对照试验注册库（CENTRAL）、医学期刊数据库（MEDLINE）、荷兰医学文摘数据库（Embase）以及其他12个数据库。我们还检索了两个试验注册库，并联系该领域的专家以获取任何正在进行或未发表的研究。
我们纳入了专门用于患有共病抽动障碍儿童的ADHD任何药物治疗的随机、双盲、对照试验。我们纳入了平行组和交叉研究设计。
我们采用Cochrane的标准方法程序，由两位综述作者独立选择研究，使用标准化表格提取数据，评估偏倚风险，并使用GRADE方法对证据的整体质量进行分级。
本综述纳入了八项随机对照试验（其中四项为交叉试验），共510名参与者（443名男孩，67名女孩）。这些研究中的参与者均为患有ADHD和慢性抽动障碍的儿童。所有研究均在美国进行，持续时间从3周到22周不等。八项研究中有五项由慈善组织或政府机构资助，或两者共同资助。一项研究由药品制造商资助。另外两项研究未说明资金来源。纳入研究的偏倚风险在盲法方面较低；在随机序列生成、分配隐藏和失访偏倚方面为低或不清楚；在选择性结果报告方面为低或高。由于重要的临床异质性和分析单位问题，我们无法将任何研究纳入Meta分析。几项试验评估了多种药物。评估的药物包括哌甲酯、可乐定、地昔帕明、右旋苯丙胺、胍法辛、托莫西汀和司来吉兰。在治疗患有抽动的儿童ADHD方面，哌甲酯、托莫西汀和可乐定的证据质量低，地昔帕明、右旋苯丙胺、胍法辛和司来吉兰的证据质量极低。除一项使用司来吉兰的研究外，所有研究均报告ADHD症状有所改善。使用胍法辛、地昔帕明、哌甲酯、可乐定以及哌甲酯与可乐定联合治疗的儿童抽动症状也有所改善。在一项研究中，抽动限制了哌甲酯进一步增加剂量。在一项研究中，高剂量右旋苯丙胺似乎会加重抽动，尽管该研究的时长仅限于三周。哌甲酯、右旋苯丙胺、托莫西汀和地昔帕明与食欲抑制或体重减轻有关。哌甲酯和右旋苯丙胺与失眠有关，可乐定与镇静有关。
在对潜在相关研究进行更新检索后，我们未发现符合纳入标准的新研究，因此我们的结论未发生变化。哌甲酯、可乐定、胍法辛、地昔帕明和托莫西汀似乎能减轻患有抽动的儿童的ADHD症状，尽管现有证据的质量低至极低。虽然在大多数抽动障碍患者中，兴奋剂尚未被证明会加重抽动，但在个别情况下，它们可能会加剧抽动。在这些情况下，使用α-激动剂或托莫西汀治疗可能是一种替代方法。尽管有证据表明地昔帕明可能改善儿童的抽动和ADHD，但安全问题可能会继续限制其在该人群中的使用。
