Atomoxetine--treatment of attention deficit hyperactivity disorder: beyond stimulants

Among the pharmacotherapeutic interventions for attention deficit hyperactivity disorder (ADHD), psychostimulants have been the drugs of choice for many years. However, some patients do not adequately respond to or cannot tolerate stimulant treatment. Among nonstimulants for ADHD, the most extensively studied and the only one approved for use in the United States is the norepinephrine reuptake inhibitor atomoxetine. This paper reviews atomoxetine's chemistry and putative mechanism of action, as well as its clinical pharmacokinetics, metabolism, and efficacy and safety in acute clinical trials. (c) 2004 Prous Science. All rights reserved.     

Treatment of attention deficit hyperactivity disorder in children and adolescents: safety considerations.

Despite a large body of evidence for both the validity of the diagnosis of attention deficit hyperactivity disorder (ADHD) and the efficacy of its treatment with medication, there is an equally long history of controversy. This article focuses on presenting safety information for medications approved by the US FDA for the treatment of individuals with ADHD. Stimulant medications are generally safe and effective. The common adverse effects of stimulant medications, including appetite suppression and insomnia, are usually of mild severity and manageable without stopping the medication. The more severe adverse effects such as tics or bizarre behaviours occur with low frequency and usually resolve when the medication is stopped. The possible impact on growth requires careful monitoring. Several rare but potentially severe adverse effects including sudden cardiac death and cancer following long-term treatment have been reported; however, these effects have not been adequately demonstrated to be of significant concern at this time. Atomoxetine also has a mild adverse effect profile in terms of severity and frequency although the numbers of studies and years of clinical experience is considerably less with this drug than for the stimulant medications. When the risks are juxtaposed to the clear efficacy in significantly reducing dysfunctional symptoms of ADHD, benefit-risk analyses support the continued use of these pharmacological treatments for patients with ADHD.     

Review of long-acting stimulants in the treatment of attention deficit hyperactivity disorder

A number of long-acting medications for the treatment of attention deficit hyperactivity disorder (ADHD) have recently been developed and approved for use in the US. These compounds are intended to optimize and maintain ADHD symptom control throughout the day, while eliminating problems associated with short-acting medications, such as the need for in-school, midday or multiple daily doses. Recent reports confirm that the safety and tolerability of long-acting medications are similar to those of short-acting medications, although long-acting medications appear to have a lower risk of abuse and diversion and may be associated with significant improvements in medication adherence. Distinctions can be made among the long-acting medications with regard to the onset, magnitude and duration of their clinical effects. Recognition of these differences is important for individualizing treatment for patients with ADHD.     

儿童注意缺陷、多动障碍的药物治疗

注意缺陷、多动障碍 (ADHD)是儿童期最为常见的一种心理行为疾病 ,药物治疗是ADHD主要的治疗方法之一。中枢兴奋药是治疗ADHD最常用的药物 ,作用快、疗效好 ,且不良反应较少。可乐定和抗抑郁剂也有较好的治疗效果 ,可乐定主要适用于伴抽动或情绪异常的ADHD病儿 ,而抗抑郁剂多用于伴抑郁或焦虑的ADHD病儿 ,但不良反应较明显。本文还介绍了近年来出现的一些治疗AD HD的新药     

AOD use and attention deficit/hyperactivity disorder

Children with attention deficit/hyperactivity disorder (ADHD) often continue to exhibit significant impairment in academic, occupational, and social functioning throughout adulthood. In addition, children with ADHD are at increased risk for developing alcoholism and other drug addictions, especially if alcoholism or ADHD exists in other family members. Alcohol and other drug (AOD) abuse may develop earlier in life (i.e., in midadolescence) when ADHD is accompanied by certain behavioral or mood disorders. The nature of the link between ADHD and AOD use disorder is unknown, although the association may be mediated by the co-occurring disorders just mentioned. In addition, ADHD-related AOD abuse may develop initially as an attempt to alleviate symptoms of mental distress associated with chronic failure, feelings of inadequacy, and conflict with parents and peers. Therapeutic intervention should incorporate both addiction and mental health treatment, including appropriate use of psychiatric medications.     

Use of moclobemide in children with attention deficit hyperactivity disorder

A monoamine oxidase hypothesis for the cause of attention deficit hyperactivity disorder has recently been established (Shekim et al. 1986). To test this, moclobemide, a new and reversible inhibitor of monoamine oxidase-A, was administered to 12 children between the ages of 6 and 13 years, diagnosed as attention deficit hyperactive according to DSM III-R, in a 4-week study. All had previously discontinued treatment with methylphenidate due to side-effects. A 40% improvement in parental assessment of children's behaviour occurred among those who received moclobemide as outpatients, and a 31% improvement among the five in-patients. There was a general increase in concentration and attention span at the end of the trial, but mood changes and explosive behaviour continued to be present at a low level. Brain mapping after moclobemide treatment showed an overall reduction in frontal lobe delta activity. Moclobemide was well tolerated by these patients, although two complained of mild gastrointestinal disturbances during the first week of therapy.     

儿童注意力缺陷多动障碍的诊断与治疗

儿童注意力缺陷多动障碍是一种影响终身的慢性神经精神疾病,儿童具有注意缺陷或多动、冲动等 6 条以上症状,至少已持续 6 个月方可诊断。诊断时注意与儿童其他疾病的鉴别。该病的治疗必须药物、行为矫治并重,对家长的培训和学校干预也应并重。     

托莫西汀和阿立哌唑治疗儿童注意缺陷多动障碍的疗效比较

目的比较托莫西汀和阿立哌唑治疗儿童注意缺陷多动障碍的临床疗效。方法收集2015年1月—2016年1月在大连市第七人民医院诊治的88例注意缺陷多动障碍患者,根据用药方案的不同分为对照组和治疗组,每组各44例。对照组患儿口服阿立哌唑片,1片/次,每晚1次。治疗组患儿口服盐酸托莫西汀胶囊,初始剂量为每天0.5 mg/kg,治疗过程中根据临床反应及耐药性进行剂量调整,每天最大剂量为1.4 mg/kg。两组患儿均连续治疗6周。比较两组患儿临床效果、SNAP-IV量表评分、数字划消失误率和Conners父母量表测验结果。结果治疗后,对照组和治疗组的总有效率分别为81.82%、97.73%,两组总有效率比较差异具有统计学意义(P0.05)。治疗后,两组患儿SNAP-IV量表评分、数字划消失误率和Conners父母量表测验结果均显著改善,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组患儿上述观察指标比对照组的改善更明显,两组比较差异有统计学意义(P0.05)。结论托莫西汀治疗注意缺陷多动障碍临床效果显著,有利于患者认知功能的改善,具有一定的临床推广应用价值。     

儿童注意缺陷多动障碍的“肾系”病机研究

目的:在全面分析临床资料的基础上揭示注意缺陷多动障碍(ADHD)的中医证候规律和病机核心。方法:采取横断面回顾性研究方法,对符合研究标准的170例初次就诊的ADHD患儿进行6个方面的临床因素调查和分析。结果:中医证型分布显示以肾精不足、脑髓失养型为主,而无证可辨型与肾虚肝旺、阴虚阳亢型所占比例相当;中医证型分布与疾病严重程度呈显著正相关趋势(P<0.01);西医亚型与中医证型分布呈显著正相关趋势(P<0.01)。结论:ADHD病位在脑,核心病机是肾虚、脑髓不充、发育落后;中医证候分型可能与西医亚型有特定对应关系;在"肾系"辨证中,与先天不足关系最为密切的ADHD两类证型:肾精不足、脑髓失养型和肾虚肝旺、阴虚阳亢型之间可能并非是平行的关系,而是一种具有逻辑顺序的前后发展关系,而最早期有可能表现为无证可辨型,在同一脏腑体系中(本研究即"肾系")各证型间的转化趋势体现了本病的中医证候变化规律。     

Psychiatric comorbidities in children with attention deficit hyperactivity disorder: implications for management

Attention deficit hyperactivity disorder (ADHD) is frequently comorbid with a variety of psychiatric disorders. These include oppositional defiant disorder and conduct disorder (CD), as well as affective, anxiety, and tic disorders. ADHD and ADHD with comorbid CD appear to be distinct subtypes; children with ADHD/CD are at higher risk of antisocial personality and substance abuse as adults. Stimulants are often effective treatments for aggressive or antisocial behavior in patients with ADHD, but mood stabilizers or atypical antipsychotics may be used to treat explosive aggressive outbursts. Response to stimulants is not affected by comorbid anxiety, but children with ADHD/anxiety disorder may show greater benefit from psychosocial interventions than those with ADHD alone. The degree of prevalence of major depressive disorder (MDD) and bipolar disorder among children with ADHD is controversial, but a subgroup of severely emotionally labile ADHD children who present serious management issues for the clinician clearly exists. Antidepressants may be used in conjunction with stimulants to treat MDD, while mood stabilizers and atypical antipsychotics are often required to treat manic symptoms or aggression. After resolution of the manic episode, stimulant treatment of the comorbid ADHD may be safely undertaken. Recent research suggests that stimulants can be safely used in children with comorbid ADHD and tic disorders, but the addition of anti-tic agents to stimulants is often necessary. Clinicians who work with patients with ADHD should be prepared to deal with a wide range of emotional and behavioral problems beyond the core symptoms of inattention and impulsivity/hyperactivity.     

Background,clinical features and treatment of attention deficit hyperactivity disorder in children

Introduction: Attention deficit hyperactivity disorder (ADHD) is an early onset, clinically heterogeneous, complex neurobiological disorder, defined by symptoms of inattention and hyperactivity/impulsivity and has been associated with a broad range of impairments for those affected. Additionally, ADHD in children and adolescents is frequently associated with psychiatric comorbidities. This review provides an overview of the epidemiology, neurobiology, genetics, diagnosis and most recent pharmacological approaches for treatment with a focus on safety and efficacy and describes the use of medications used to treat ADHD in special populations.

Areas covered: PubMed, Cochrane database, Essential Evidence and Uptodate were searched for relevant articles about stimulant and non-stimulant pharmacological approaches in ADHD.

Expert opinion: Data supporting the safety and efficacy of both stimulant and non-stimulant formulations have significantly grown over the past decade and more efforts are being made to tailor medications to the needs of the patients and their families. Pharmacogenomics research is evolving, but predictors of treatment response and side effects remain largely unknown. Other unmet clinical needs include long-term follow-up studies of the safety and efficacy of medications for those with ADHD alone, or with comorbidities and in special populations including preschoolers.     

Clinical and neuropsychological effects of desipramine in children with attention deficit hyperactivity disorder

Desipramine is a tricyclic antidepressant with demonstrated efficacy for some children with attention deficit hyperactivity disorder (ADHD). In this controlled study, clinical improvement was noted in a group of 12 ADHD children. There also were neuropsychological effects associated with desipramine treatment: a small but significant decline in motor performance and an improvement in long-term verbal memory. The decline in motor performance may be of only limited clinical significance, but it is an effect that desipramine seems to share with other tricyclic antidepressants. The improvement in memory performance is an effect it shares with the psychostimulants.     

Stimulants: use and abuse in the treatment of attention deficit hyperactivity disorder

Attention deficit hyperactivity disorder (ADHD) is the most prevalent childhood developmental disorder and is also of unclear neurobiological aetiology. However, recent advances in molecular genetics and brain imaging implicate dopaminergic hypofunction in the frontal lobes and basal ganglia in ADHD. Psychostimulants (e.g. methylphenidate and amphetamine, which are potent inhibitors of the dopamine transporter) are the first choice medication for ADHD and have a good acute efficacy and safety profile when used for this disorder. Whether long-term psychostimulant administration to adolescents alters neural development and behaviour or increases the risk of substance abuse is less certain. The precise molecular mechanism of action of psychostimulants is beginning to be established. Furthermore, preclinical studies have begun to use lower clinically relevant doses and oral administration of psychostimulants to determine their long-term effect on development, behaviour and neurochemistry, which is an important public health issue associated with chronic medication of adolescents with ADHD.     

Effects of methylphenidate on multiple components of attention in children with attention deficit hyperactivity disorder

Rationale Methylphenidate (MPH) has been shown to be effective in the treatment of attention deficits in children with attention deficit hyperactivity disorder (ADHD). Although a variety of studies have been performed, there is little available information as to which components of attentional functioning are disturbed in ADHD.Objectives The aim of the present study was to monitor the effect of MPH on various measures of attention in children with ADHD.Methods In a double-blind, placebo-controlled, crossover study, the attentional functioning of 58 children diagnosed with ADHD without psychiatric comorbidity was examined. Assessment of attention was performed on their usual MPH treatment and following withdrawal of the drug. Furthermore, the attentional performance of 58 healthy children was assessed. The test battery consisted of reaction time tasks, including measures of alertness, vigilance, divided attention, flexibility, and aspects of selective attention such as focused attention, inhibition, and integration of sensory information.Results In comparison to the test performance of healthy children, children with ADHD displayed impairments of vigilance, divided attention, flexibility, and aspects of selective attention including focused attention, inhibition, and integration of sensory information. Statistical comparison of attentional functioning of children with ADHD on and off MPH treatment revealed that the medication resulted in an improved task accuracy regarding vigilance, divided attention, inhibition, focused attention, integration of sensory information, and flexibility. Conclusion The present findings indicate that various aspects of attention are markedly impaired in children with ADHD. Treatment with MPH was accompanied by improvements in attention functions of small to moderate sizes. Although MPH-induced improvements were observed in a broad range of attention measures, children with ADHD who were on MPH treatment nevertheless displayed serious deficits in a number of components of attention.     

学龄期注意缺陷多动障碍儿童行为问题的研究

目的分析学龄期注意缺陷多动障碍（ Attention Deficit Hyperactivity Disorder, ADHD）儿童的行为问题。方法对82例ADHD儿童和82例正常组儿童进行对照研究,应用Conner’s儿童行为父母问卷及CBCL（ Children Behavior Check List）对所有受试者进行行为评定。结果Conner’s父母问卷和CBCL评定量表中,ADHD组在品行问题、学习问题、冲动-多动和多动指数、攻击性、多动因子得分和总分分别与对照组比较,差异均有统计学意义（P〈0．05）。结论学龄期ADHD儿童大多伴有行为问题,应重视早期干预和治疗。     

Inositol may worsin attention deficit disorder with hyperactivity

Antidepressant drugs have been reported to improve ADDH symtomatology. Myoinositol is a simple isomer of glucose and is the precursor of the phosphatidylinositol second messenger system in brain. Both α₁-adrenergic and 5HT₂ receptors activate this second messenger system. Recently, we found inositol to be effective in depression. Therefore we decided to evaluate the effects of oral inositol in children with ADDH in a double-blind, cross-over, placebo-controlled manner. Eleven children, mean age 8.9 ± 3.6 years with a mean illness duration of 4.5 ± 2.8 years were enrolled in an 8-week trial. Inositol or dextrose (placebo) was dispensed in powder form at a dose of 200 mg/kg aggravation of the syndrome with myo-inositol as compared to placebo.