Attention deficit and hyperactivity disorder: controversies of diagnosis and safety of pharmacological and nonpharmacological treatment

Attention-Deficit and Hyperactivity Disorder (ADHD) is a condition that presents with a variety of behavioral and social problems. The objective of this review was to examine the evidence concerning the controversies surrounding the diagnosis of ADHD and the safety of pharmacological and nonpharmacological treatment. A MEDLINE search was conducted using MeSH terms ADHD, children, treatments or behavioral therapy. The search was limited to January 1990 to present, randomized clinical trials, retrospective studies and English. Fifty-seven articles were selected for review. Controversies exist regarding the diagnosis: variations exist by gender, across countries and by method of diagnosis. These issues are currently unresolved. The interventions with the most data concerning their safety and efficacy in children were stimulant medications. Children with ADHD who took stimulant medications showed the greatest improvement in behavior when compared to other interventions such as behavior therapy or family counseling. Limitations of behavior therapy included that it is often a difficult process to continue on an ongoing basis and only a portion of the therapy stimulated the child's natural reward system. However, a combination of both stimulant medication and behavior therapy demonstrated synergistic efficacy. Care must be taken to insure that issues of gender and race, as well as the adverse effects of treatment options, are adequately taken into account by the treating clinician.     

Long-term use of stimulants in children with attention deficit hyperactivity disorder: safety, efficacy, and long-term outcome

The purpose of this review is to summarize existing data on the long-term safety and efficacy of stimulant treatment, and how long-term stimulant treatment of children with attention deficit hyperactivity disorder (ADHD) affects their outcome. Existing controlled studies of children with ADHD treated and untreated with stimulants, as well as long-term prospective follow-up studies, are reviewed. Children with ADHD treated with stimulants for as long as 2 years continue to benefit from the treatment, with improvements observed in ADHD symptoms, comorbid oppositional defiant disorder, and academic and social functioning, with no significant problems of tolerance or adverse effects. Long-term, prospective follow-up studies into adulthood show that stimulant treatment in childhood has slight benefits regarding social skills and self-esteem. Long-term adverse effects from stimulant treatment in childhood regarding adult height or future substance abuse have not been supported by existing studies.     

Pharmacotherapy of adolescent attention deficit hyperactivity disorder: challenges, choices and caveats

A recent increase in stimulant treatment of adolescents with attention deficit hyperactivity disorder (ADHD) has been documented. Challenges in treating adolescent ADHD with methylphenidate or dextroamphetamine include compliance with frequent dosing, abuse potential and wear-off or rebound effects. Co-morbid anxiety, occurring in at least 30 percent of ADHD youths, is associated with lower rate of response to stimulants. The effective alternatives, tricyclic antidepressants or pemoline, are each associated with rare but serious toxicity. Bupropion has recently proven effective in controlled trials. Other noradrenergic or dopamine-enhancing agents such as venlafaxine and nicotine show some benefit in open trials. The need for more options in pharmacotherapy of ADHD is evidenced by rapid adoption in clinical practice of alternative and adjunctive medication despite lack of controlled research on efficacy and safety. The indications for long-term stimulant treatment of ADHD present some controversy, and highlight a need for more research on safety and efficacy through the lifespan. Thresholds for diagnosis are much lower with DSM than with ICD, and thresholds for treatment are contentious, given the performance-enhancing effects of stimulants in normal students. The endpoint for treatment is unclear, as stimulants are also effective in adult ADHD. Based on short- and intermediate-term studies to date, stimulant medication is clearly more efficacious than cognitive and behavioral strategies for the symptoms of ADHD. Longer term research is needed to determine whether sustained stimulant therapy will reduce the adverse emotional, behavioral and academic consequences of inattention and impulsivity in adolescents and adults.     

Long-term efficacy and safety of treatment with stimulants and atomoxetine in adult ADHD: A review of controlled and naturalistic studies

Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood that often persists into adulthood. Although stimulant medications are recommended as the first-line treatment for ADHD because of their documented short-term effects in children and adults, less is known about their effects on long-term outcome in adults. Here we review the long-term efficacy and safety of the stimulant drugs methylphenidate and amphetamine, as well as the related compound atomoxetine. We performed a systematic review to identify direct and indirect effects of stimulant therapy on long-term outcome in adults. Five randomized controlled trials (RCTs), and 10 open-label extension studies of initial short-term RCTs, with total follow-up of at least 24 weeks, were identified. All these RCTs found that medication was significantly more efficacious than placebo in treating ADHD in adults, and the extension studies showed that this favorable effect of medication was maintained during the open-label follow-up period. However, since the maximum duration of these pharmacological trials was 4 years, we also reviewed 18 defined naturalistic longitudinal and cross-sectional studies, to provide more information about longer term functional outcomes, side effects and complications. These observational studies also showed positive correlations between early recognition of the disorder, stimulant treatment during childhood and favorable long-term outcome in adult ADHD patients. In conclusion, stimulant therapy of ADHD has long-term beneficial effects and is well tolerated. However, more longitudinal studies of long duration should be performed. In addition, the ethical issues involved in performing double blind RCTs of many years duration should be further explored.     

Safety of stimulant treatment in attention deficit hyperactivity disorder: part II

Importance of the field: Attention deficit hyperactivity disorder (ADHD) is the most common childhood psychiatric disorder and in at least 50% of cases persists into adulthood. Treatment of ADHD with stimulants is one of the oldest and most effective pharmacological treatments in psychiatry. Yet, there continues to be controversy over the safety of stimulant medications in the treatment of ADHD.

Areas covered in this review: This paper is a continuation of an earlier paper that reviewed the safety profile of newer stimulant agents, especially in relation to special populations. This part II reviews, through essentially an organ-system approach, the various clinical concerns that have been raised over the safety of stimulant medications. This includes neuropsychiatric, cardiovascular effects on growth and development, and a number of other less common concerns.

What the reader will gain: A thorough review of safety concerns in stimulants that emphasizes clinical information, case reports, open series or controlled trials relating to stimulant use in the treatment of ADHD.

Take home message: While many safety concerns have been raised in the use of stimulants, the vast majority of treatment complications are either quickly reversible or easily manageable with appropriate clinical care. The negative consequences of untreated ADHD clearly outweigh the risks of the stimulant medicines when used in an appropriate and careful manner.     

Efficacy and tolerability of pharmacotherapies for attention-deficit hyperactivity disorder in adults

This review examines the evidence regarding the efficacy and tolerability of long- and short-acting stimulant medications, as well as the non-stimulant medications atomoxetine and bupropion in the treatment of adult attention-deficit hyperactivity disorder (ADHD). Effect sizes in adults appear to be of almost the same magnitude as in school-age children when robust doses are used. There are adequate data demonstrating short-term efficacy and safety of medication in ADHD during adulthood but long-term studies are lacking, particularly in view of concerns regarding cardiovascular adverse events. There is some evidence that stimulant medication can improve driving performance in adults with ADHD. The extent to which medication may improve academic, occupational and social functioning in adults with ADHD is unclear, and future research should investigate these outcomes. Medication treatment of adults with ADHD in sports is controversial. Both stimulant and non-stimulant medications seem to be well tolerated. Monitoring of pulse and blood pressure is recommended with these drugs because of their cardiovascular effects. There have been extremely rare case reports of sudden death in adults and children treated with stimulants and atomoxetine, but it is difficult to clearly establish causality. In view of reports of treatment-related suicide-related behaviour with atomoxetine, it is recommended that adults should be observed for agitation, irritability, suicidal thinking, self-harming or unusual behaviour, particularly in the first months of treatment, or after a change of dose. ADHD in adults continues to remain an under-recognized disorder in many parts of the world and there is a lack of specialist clinics for assessment and treatment of adult ADHD. Studies to date have failed to show efficacy of medications in the treatment of ADHD in the substance misuse population. There is little evidence so far to suggest an increased misuse of stimulants or diversion amongst substance misusers; however, data are insufficient to draw firm conclusions. Further work is necessary to evaluate effective treatments in subgroups such as the substance misuse population, those with multiple co-morbidities and different ADHD subtypes.     

New formulations of stimulants for attention-deficit hyperactivity disorder: therapeutic potential

New formulations of stimulant medications for the treatment of attention-deficit hyperactivity disorder (ADHD) have been an important focus for pharmaceutical industry research and development over the past decade. In this article, we review and assess the therapeutic potential of five new stimulant formulations (one immediate release and four longer-acting preparations) that have recently become available for the treatment of ADHD.While the therapeutic potential of immediate-release enantiomers of methylphenidate has not yet been clinically realised, new long-acting formulations of stimulants have changed the standard of care for children, adolescents and adults with ADHD. The longer duration of action of these once-daily compounds, and the consequent expansion of the duration of daily ADHD coverage afforded by them, has introduced the realistic possibility of reducing the overall daily burden of ADHD on affected individuals. Although more expensive, these new stimulant formulations are easier for patients to use than older stimulants, more resistant to abuse and misuse, and allow for increased privacy of ADHD treatment at school or work.     

盐酸哌甲酯控释片治疗注意缺陷多动障碍研究进展

注意缺陷多动障碍是一种儿童期常见的精神障碍，中枢兴奋剂如盐酸哌甲酯片是临床治疗此类障碍的一线药物。然而，由于盐酸哌甲酯片疗效持续时间较短，需要每天多次服药使治疗依从性不佳。盐酸哌甲酯控释片（专注达）是每天1次服用的渗透型控释片剂，成为治疗注意缺陷多动障碍的有价值药物。现综述其药动学、药理作用、剂型特点、临床疗效和安全性研究进展。     

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.     

Pharmacotherapy for parents with attention-deficit hyperactivity disorder (ADHD): impact on maternal ADHD and parenting

Given the high heritability of the disorder, attention-deficit hyperactivity disorder (ADHD) is common among parents of children with ADHD. Parental ADHD is associated with maladaptive parenting, negative parent-child interaction patterns and a diminished response to behavioural parent training. We describe our previous research demonstrating that stimulant medications for mothers with ADHD are associated with reductions in maternal ADHD symptoms. Although limited beneficial effects on self-reported parenting were also found in our study, the impact of ADHD medications on functional outcomes related to parenting and family interactions may not be sufficient for many families. Many questions remain with regard to how best to treat multiplex ADHD families in which a parent and child have ADHD. In particular, future studies are needed: (1) to evaluate how best to sequence pharmacotherapy, psychosocial treatment for adult ADHD and behavioural parenting interventions; (2) to determine the best approach to maintaining treatment effects over the long term for both parents and children; and (3) to identify individual predictors of treatment response.     

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.     

Dexmethylphenidate for attention deficit hyperactivity disorder

Background: Dexmethylphenidate is a single-isomer stimulant medication approved for the treatment of attention deficit hyperactivity disorder (ADHD). Single-isomer drugs have the potential for decreased undesired effects and improved therapeutic efficacy. Stimulant medications have been the mainstay treatments for ADHD for fifty years, and ability to reduce their adverse effects would be useful in promoting patient compliance with treatment. Objective: To review the literature on the safety and efficacy of dexmethylphenidate. Methods: MedLine, PubMed search of dexmethylphenidate research. Results/conclusions: Dexmethylphenidate is a safe and effective treatment for ADHD. Its overall safety and tolerability profile is similar to other members of the psychostimulant class.     

Comparison of the inhibitory and excitatory effects of ADHD medications methylphenidate and atomoxetine on motor cortex.

Stimulant and norepinephrine (NE) reuptake inhibitor medications have different effects at the neuronal level, but both reduce symptoms of attention deficit hyperactivity disorder (ADHD). To understand their common physiologic effects and thereby gain insight into the neurobiology of ADHD treatment, we compared the effects of the stimulant methylphenidate (MPH) and NE uptake inhibitor atomoxetine (ATX) on inhibitory and excitatory processes in human cortex. Nine healthy, right-handed adults were given a single, oral dose of 30 mg MPH and 60 mg ATX at visits separated by 1 week in a randomized, double-blind crossover trial. We used paired and single transcranial magnetic stimulation (TMS) of motor cortex to measure conditioned and unconditioned motor-evoked potential amplitudes at inhibitory (3 ms) and facilitatory (10 ms) interstimulus intervals (ISI) before and after drug administration. Data were analyzed with repeated measures, mixed model regression. We also analyzed our findings and the published literature with meta-analysis software to estimate treatment effects of stimulants and NE reuptake inhibitors on these TMS measures. There were no significant pretreatment differences or effects of treatment order. Both agents produced a significant increase in facilitation and a decrease in inhibition. Effects of ATX and MPH did not differ significantly. Pooled estimates from published studies show similar results for stimulants and NE reuptake inhibitors. In conclusion, in healthy adults, both stimulant and nonstimulant medications for ADHD decrease cortical inhibition and increase cortical facilitation. Cortical inhibition, shown previously to be abnormal in ADHD, may play a key role producing behavioral pathology.     

Testing computational models of dopamine and noradrenaline dysfunction in attention deficit/hyperactivity disorder.

We test our neurocomputational model of fronto-striatal dopamine (DA) and noradrenaline (NA) function for understanding cognitive and motivational deficits in attention deficit/hyperactivity disorder (ADHD). Our model predicts that low striatal DA levels in ADHD should lead to deficits in 'Go' learning from positive reinforcement, which should be alleviated by stimulant medications, as observed with DA manipulations in other populations. Indeed, while nonmedicated adult ADHD participants were impaired at both positive (Go) and negative (NoGo) reinforcement learning, only the former deficits were ameliorated by medication. We also found evidence for our model's extension of the same striatal DA mechanisms to working memory, via interactions with prefrontal cortex. In a modified AX-continuous performance task, ADHD participants showed reduced sensitivity to working memory contextual information, despite no global performance deficits, and were more susceptible to the influence of distractor stimuli presented during the delay. These effects were reversed with stimulant medications. Moreover, the tendency for medications to improve Go relative to NoGo reinforcement learning was predictive of their improvement in working memory in distracting conditions, suggestive of common DA mechanisms and supporting a unified account of DA function in ADHD. However, other ADHD effects such as erratic trial-to-trial switching and reaction time variability are not accounted for by model DA mechanisms, and are instead consistent with cortical noradrenergic dysfunction and associated computational models. Accordingly, putative NA deficits were correlated with each other and independent of putative DA-related deficits. Taken together, our results demonstrate the usefulness of computational approaches for understanding cognitive deficits in ADHD.     

Substance abuse in patients with attention-deficit hyperactivity disorder : therapeutic implications

Attention-deficit hyperactivity disorder (ADHD) is a common disorder in children that frequently persists into adulthood. Studies have found that substance use disorders (SUD) are seen more commonly in those with ADHD than the general population. Although treatment with stimulant medications has been shown to be effective for individuals with ADHD, concern about the use of these agents in this population persists. This review article highlights the research in this area with a focus on the treatment of individuals who present with concomitant ADHD and SUD. Although stimulants can be abused, studies have shown that adolescents who are prescribed stimulants for ADHD have lower rates of SUD than those who are not treated with stimulants. It may be particularly difficult to evaluate adults for the diagnosis of ADHD when SUD is a co-morbid factor. Studies show that 20--30% of adults presenting with SUD have concomitant ADHD and approximately 20--40% of adults with ADHD have histories of SUD. Therefore, it is critical to perform careful diagnostic interviews to discern if patients have either or both of these disorders. Many clinical experts suggest that adults with ADHD and active SUD be treated for the SUD until a period of sobriety persists prior to initiation of specific treatment for ADHD. Since individuals with ADHD and active SUD are more likely to have more severe SUD and a worse prognosis, this approach may not serve many patients, as they relapse prior to obtaining ADHD treatment. Therefore, research has been directed towards determining if the treatment of ADHD with stimulant medications can be safe and effective for the individual with active SUD and concomitant ADHD. An initial trial of methylphenidate in a population of adults with active cocaine dependence and ADHD indicates that this is the case. Individuals with ADHD and SUD can present difficult diagnostic and therapeutic challenges. It appears that the most effective treatment option is to create a programme that uses the most effective treatment modalities available, including both behavioural and medical therapies, along with close supervision and monitoring. Newer medical treatment options of long-acting stimulants and non-stimulants (e.g. atomoxetine) offer effective treatment with a lower risk of abuse potential.     

Impact of Central Nervous System Stimulant Medication Use on Growth in Pediatric Populations with Attention-Deficit/Hyperactivity Disorder: A Review

Central nervous system stimulants are a commonly used first-line treatment option for attention-deficit/hyperactivity disorder (ADHD). Stimulants are generally well tolerated, with anorexia and insomnia the most common adverse effects. However, there are some concerns with long-term use of stimulants, such as potential growth delay. Historically, data regarding this long-term adverse effect have been conflicting. In this article, we review the newer data surrounding the effects of central nervous system stimulants on growth parameters in children with ADHD. We conducted a literature search of the PubMed database; only articles using ADHD criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included to ensure the most up-to-date review of literature. Nine articles were identified for relevance and quality and are discussed in this review, describing clinical observations of height and weight of adolescent or pediatric patients receiving stimulant medications for ADHD therapy. In summary, this review points toward potential associations between duration of treatment and higher doses of stimulants with decreased weight and body mass index. Furthermore, this review demonstrates that evidence is still conflicting regarding the relationship between stimulant use and significant height decreases. Future studies with higher quality of evidence are needed to observe this potential adverse effect of stimulants in children and adolescents.     

A qualitative review of issues arising in the use of psycho­stimulant medications in patients with ADHD and co‑morbid substance use disorders

ABSTRACT

Objective: This review addresses the relationship between attention-deficit/hyperactivity disorder (ADHD) and substance use disorders (SUDs), with an emphasis on factors that determine the potential for psychostimulant abuse. Strategies for identification and treatment of patients with ADHD who are at risk for, or have, co-morbid SUD are also addressed.

Research design and methods: The article was based on a qualitative review of current literature addressing co-morbid ADHD and SUD.

Discussion: Adolescent and adult patients with ADHD are at increased risk for SUD, as well as a number of other psychiatric disorders. Psychostimulant agents like methyl­phenidate (MPH) and mixed amphetamine salts (MAS) are effective first-line pharmacotherapies for ADHD; however, they are Schedule II controlled substances with a potential for abuse. Evidence suggests that treatment of ADHD during childhood with stimulant agents may reduce the risk of developing SUD later on. Factors associated with the highest risk of SUD in patients with ADHD include co-morbid antisocial personality disorder, bipolar disorder, an eating disorder, severe ADHD and/or antisocial behavior symptoms, and dropping out of school. Treatment initiation during adolescence or young adulthood also has been linked to increased risk of polydrug use and non-medical stimulant use, a pattern of behavior consistent with a risk of SUD development. Treatment plans for patients with ADHD and co-morbid SUD should include behavioral interventions, careful monitoring, and when appropriate, pharmacotherapy. When oral formulations of psychostimulants are used at recommended doses and frequencies, they are unlikely to yield effects consistent with abuse potential in patients with ADHD. Long-acting stimulant formulations and non-stimulants, like atomoxetine or bupropion, have a lower potential for abuse, and provide several safe and effective treatment options for the development of a comprehensive manage­ment plan for patients with co-morbid ADHD and SUD.

Conclusions: The present review is neither exhaustive nor systematic. Moreover, the reviewed studies vary wide­ly with regards to methodology and patient populations. In light of these limitations, several conclusions are still warranted. Patients with ADHD are at increased risk for SUD. Under certain conditions, psychostimulants may be a pharmacologic option in the treatment of patients with co-morbid ADHD and SUD. However, clinicians should be mindful of the risks and benefits of this treatment approach in a high-risk population and should also bear in mind the labeling guidelines when working with this co-morbidity.     

Gamma-frequency neuronal activity is diminished in adults with attention-deficit/hyperactivity disorder: a pharmaco-MEG study

Attention-deficit/hyperactivity disorder (ADHD) is a neurobehavioral disorder affecting approximately 4-7% of children and persisting in 2-5% of adults. The core symptoms include pervasive inattention and inappropriate levels of hyperactivity-impulsivity. High-frequency gamma activity has been implicated in the temporal binding of stimulus properties across cortical areas, and is known to be crucial for complex information processing and attentional processes in particular. Thus, we evaluated the amplitude of gamma-frequency neural responses in adults with and those without ADHD, and tested whether stimulant medications, the most common treatment for ADHD, modulate gamma activity in affected adults. Participants underwent two sessions (~75 min apart) of auditory stimulation using stimuli known to elicit 40 Hz gamma-band responses as magnetoencephalography data were acquired. Between sessions, the ADHD group (who were in maintenance therapy) were administered their daily stimulant medication and both groups were told to relax. The primary results indicated that gamma activity was weaker in the ADHD group during session one (pre-drug), but not session two (post-drug), and that gamma activity significantly increased following stimulant administration in adults with ADHD. These results suggest that ADHD is associated with reduced cortical gamma activity and that stimulants may ameliorate this abnormality.     

Symptoms of Depression and ADHD in Relation to Stimulant Medication Misuse Among College Students

Background: The misuse of stimulant medications, commonly used for the treatment of attention-deficit/hyperactivity disorder (ADHD), is a concern on college campuses. Objective: This study sought to examine the relations between the misuse of stimulant medications and symptoms of depression and ADHD. Method: Eight hundred and ninety students ages 18–26 from one public university took a web-based survey including rating scales measuring symptoms of depression and ADHD. Results: The prevalence rate of misuse in the past year was 23%. Symptoms of depression were significantly related to misuse; however, once symptoms of ADHD were included in the analysis, depression was no longer a significant predictor. Further, there was not a significant interaction between ADHD and depression, but symptoms of ADHD were significantly related to misuse. Conclusions/Importance: Results suggest that attention difficulties may be one of the most important factors in predicting stimulant medication misuse. Therefore, prevention efforts to reduce the misuse of stimulant medication would be most successful when targeting students with symptoms of inattention.     

Effects of stimulant medications on the EEG of children with attention-deficit/hyperactivity disorder

Abstract Rationale. Stimulant medications are the most commonly used treatments for attention deficit/hyperactivity disorder (ADHD) in North America and Australia, although it is still not entirely known how these medications work. Objectives. This study aimed to investigate the effects of stimulant medications on the EEG of children with the Combined subtype of ADHD. Method. An initial EEG was recorded during an eyes-closed resting condition and Fourier transformed to provide absolute and relative power estimates for the delta, theta, alpha and beta bands. Theta/alpha and theta/beta ratios were also calculated. Subjects were placed on a 6-month trial of a stimulant and a second EEG was recorded at the end of the trial. Results. The ADHD group had significantly greater absolute delta and theta, less posterior absolute beta, more relative theta, and less relative alpha than the control group, which is typical of EEG studies of children with ADHD. The use of stimulant medications resulted in normalisation of the EEG, primarily evident in changes in the theta and beta bands. Conclusions. These results suggest that stimulants act to increase cortical arousal in children with ADHD, normalising their brain activity. Electronic Publication