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Introduction

Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3-5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2007 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 34 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega 3-polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).

Key Points

Core symptoms of ADHD are inattention, hyperactivity, and impulsiveness, although other conditions frequently coexist with ADHD, including developmental disorders (especially motor, language, social communication, and specific learning disabilities) and psychiatric disorders (especially oppositional defiant and conduct disorder, anxiety, and depressive disorders). Symptoms must be present for at least 6 months, are generally observed in children before the age of 7 years, and cause clinically important impairment in social, academic, or occupational functioning which must be evident in more than one setting.Formal diagnostic criteria are most applicable to boys aged 6-12 years, and most research data relate to this group. Preschool children, adolescents, and females may present less-typical features, but similar levels of impairment. Prevalence estimates among school children range from 3% to 5%.

Methylphenidate improves core symptoms and school performance in children with ADHD when used alone.

Dexamfetamine and atomoxetine may also reduce symptoms of ADHD.

We don't know how effective any treatment for ADHD is in the long term; people with ADHD may require treatment for many years.

CAUTION: Atomoxetine may cause rare but serious liver injury.

Clonidine and modafinil may improve symptoms of ADHD compared with placebo, but are associated with an increased risk of adverse effects compared with methylphenidate, dexamfetamine, and atomoxetine.

We don't know whether homeopathy, bupropion, or polyunsaturated fatty acids are beneficial in the treatment of symptoms of ADHD.

We don't know how effective psychological/behavioural treatments alone are compared with each other or with pharmacological treatments, as we found few high-quality studies. The combination of methylphenidate plus psychological treatment may enhance effectiveness of methylphenidate alone or behavioural treatment alone, but we don't know whether dexamfetamine plus psychological treatment is effective in treatment of ADHD compared with either intervention alone. Long-term outcome for both drug treatment alone and combination treatments is uncertain.We don't know whether parent training in conjunction with teacher involvement is more effective than parent training alone.

Introduction

Prevalence estimates of attention deficit hyperactivity disorder (ADHD) vary according to the diagnostic criteria used and the population sampled. DSM-IV prevalence estimates among school children in the US are 3% to 5%, but other estimates vary from 1.7% to 16.0%. No objective test exists to confirm the diagnosis of ADHD, which remains a clinical diagnosis. Other conditions frequently co-exist with ADHD.

Methods and outcomes

We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmacological treatments for ADHD in children and adolescents? What are the effects of psychological treatments for ADHD in children and adolescents? What are the effects of combination treatments for ADHD in children and adolescents? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).

Results

We found 70 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.

Conclusions

In this systematic review we present information relating to the effectiveness and safety of the following interventions: atomoxetine, bupropion, clonidine, dexamfetamine sulphate, homeopathy, methylphenidate, modafinil, omega-3 polyunsaturated fatty acids, and psychological/behavioural treatment (either alone or in combination with a drug treatment).

Key Points

Core symptoms of ADHD are inattention, hyperactivity, and impulsiveness, although other conditions frequently co-exist with ADHD, including developmental disorders (especially motor, language, social communication, and specific learning disabilities) and psychiatric disorders (especially oppositional defiant and conduct disorder, anxiety, and depressive disorders). Symptoms must be present for at least 6 months, are generally observed in children before the age of 7 years, and cause clinically important impairment in social, academic, or occupational functioning that must be evident in more than one setting.Formal diagnostic criteria are most applicable to boys aged 6 to 12 years, and most research data relate to this group. Pre-school children, adolescents, and females may present less typical features, but similar levels of impairment. Prevalence estimates among school children range from 3% to 5%.

Methylphenidate improves core symptoms in children with ADHD when used alone.

Dexamfetamine and atomoxetine may also reduce symptoms of ADHD.

We don't know how effective any treatment for ADHD is in the long term; people with ADHD may require treatment for many years.

CAUTION: Atomoxetine may cause rare but serious liver injury.

Clonidine and modafinil may improve symptoms of ADHD compared with placebo, but are associated with an increased risk of adverse effects compared with methylphenidate, dexamfetamine, and atomoxetine.

We don't know whether homeopathy, bupropion, or omega-3 polyunsaturated fatty acids are beneficial in the treatment of symptoms of ADHD.

We don't know how effective psychological/behavioural treatments alone are compared with each other or with pharmacological treatments, as we found few high-quality studies. The combination of methylphenidate plus psychological treatment may enhance effectiveness of methylphenidate alone or behavioural treatment alone, but we don't know whether dexamfetamine plus psychological treatment is effective in treatment of ADHD compared with either intervention alone. Long-term outcome for both drug treatment alone and combination treatments is uncertain.We don't know whether parent training in conjunction with teacher involvement is more effective than parent training alone.

Background

Compared to existing literature on childhood attention deficit hyperactivity disorder (ADHD), little published adult data are available, particularly outside of the United States. Using General Practitioner (GP) questionnaires from the United Kingdom, this study aimed to examine a number of issues related to ADHD in adults, across three cohorts of patients, adults who received ADHD drug treatment in childhood/adolescence but stopped prior to adulthood; adults who received ADHD drug treatment in childhood/adolescence and continued treatment into adulthood and adults who started ADHD drug treatment in adulthood.

Methods

Patients with a diagnosis of ADHD and prescribed methylphenidate, dexamfetamine or atomoxetine were identified using data from The Health Improvement Network (THIN). Dates when these drugs started and stopped were used to classify patients into the three cohorts. From each cohort, 50 patients were randomly selected and questionnaires were sent via THIN to their GPs.

GPs returned completed questionnaires to THIN who forwarded anonymised copies to the researchers. Datasets were analysed using descriptive statistics.

Results

Overall response rate was 89% (133/150). GPs stated that in 19 cases, the patient did not meet the criteria of that group; the number of valid questionnaires returned was 114 (76%). The following broad trends were observed: 1) GPs were not aware of the reason for treatment cessation in 43% of cases, 2) patient choice was the most common reason for discontinuation (56%), 3) 7% of patients who stopped pharmacological treatment subsequently reported experiencing ADHD symptoms, 4) 58% of patients who started pharmacological treatment for ADHD in adulthood received pharmacological treatment for other mental health conditions prior to the ADHD being diagnosed.

Conclusion

This study presents some key findings relating to ADHD; GPs were often not aware of the reason for patients stopping ADHD treatment in childhood or adolescence. Patient choice was identified as the most common reason for treatment cessation. For patients who started pharmacological treatment in adulthood, many patients received pharmacological treatment for comorbidities before a diagnosis of ADHD was made.

Background

ADHD guidelines in the UK suggest that children and adults who respond to pharmacological treatment should continue for as long as remains clinically effective, subject to regular review. To what extent patients persist with treatment from childhood and adolescence into adulthood is not clear. This study aims to describe, in UK primary care, the persistence of pharmacological treatment for patients with ADHD who started treatment aged 6–17 years and to estimate the percentage of patients who continued treatment from childhood and adolescence into adulthood.

Methods

The Health Improvement Network (THIN) database was used to identify patients with ADHD who received their first prescription for methylphenidate/ dexamfetamine/atomoxetine, aged 6–17 years. Patients were monitored until their ‘censored date’ (the earliest of the following dates: date the last prescription coded in the database ended, end of the study period (31st December 2008), date at which they transferred out of their practice, date of death, the last date the practice contributed data to the database). Persistence of treatment into adulthood was estimated using Kaplan Meier analysis.

Results

610 patients had follow-up data into adulthood. 213 patients (93.4% male) started treatment between 6–12 years; median treatment duration 5.9 years. 131 (61.5%) stopped before 18 years, 82 (38.5%) were still on treatment age ≥18 years. 397 patients (86.4% male) started treatment between 13–17 years; median treatment duration was 1.6 years. 227 (57.2%) stopped before 18 years, 170 (42.8%) were still on treatment age ≥18 years. The number of females in both age categories was too small to formally test for differences between genders in persistence of treatment.

Conclusion

Persistence of treatment into adulthood is lower (~40%) compared with published rates of persistence of the condition (~65% when symptomatic definition of remission used). Due to the limited number of patients with data past 18 years, it is important that ongoing monitoring of prescribing into later adulthood is undertaken, particularly to observe the effects of recommendations in new guidelines.

Attention deficit hyperactivity disorder is a developmental disorder with an age onset prior to 7 years. Children with ADHD have significantly lower ability to focus and sustain attention and also score higher on impulsivity and hyperactivity. Stimulants, such as methylphenidate, have remained the mainstay of ADHD treatment for decades with evidence supporting their use. However, recent years have seen emergence of newer drugs and drug delivery systems, like osmotic release oral systems and transdermal patches, to mention a few. The use of nonstimulant drugs like atomoxetine and various other drugs, such as α-agonists, and a few antidepressants, being used in an off-label manner, have added to the pharmacotherapy of ADHD. This review discusses current trends in drug therapy of ADHD and highlights the promise pharmacogenomics may hold in the future.

Background

Attention Deficit/Hyperactivity Disorder (ADHD) is a neurobehavioural disorder, affecting 3–6% of school age children and adolescents in Spain. Methylphenidate (MPH), a mild stimulant, had long been the only approved medication available for ADHD children in Spain. Atomoxetine is a non-stimulant alternative in the treatment of ADHD with once-a-day oral dosing. This study aims to estimate the cost-effectiveness of atomoxetine compared to MPH. In addition, atomoxetine is compared to 'no medication' for patient populations who are ineligible for MPH (i.e. having stimulant-failure experience or co-morbidities precluding stimulant medication).

Methods

An economic model with Markov processes was developed to estimate the costs and benefits of atomoxetine versus either MPH or 'no medication'. The incremental cost per quality-adjusted life-year (QALY) was calculated for atomoxetine relative to the comparators. The Markov process incorporated 14 health states, representing a range of outcomes associated with treatment options. Utility values were obtained from the utility valuation survey of 83 parents of children with ADHD. The clinical data were based on a thorough review of controlled clinical trials and other clinical literature, and validated by international experts. Costs and outcomes were estimated using Monte Carlo simulation over a 1-year duration, with costs estimated from the perspective of the National Health Service in Spain.

Results

For stimulant-naïve patients without contra-indications to stimulants, the incremental costs per QALY gained for atomoxetine were € 34 308 (compared to an immediate-release MPH) and € 24 310 (compared to an extended-release MPH). For those patients who have stimulant-failure experience or contra-indications to stimulants, the incremental costs per QALY gained of atomoxetine compared to 'no medication' were € 23 820 and € 23 323, respectively.

Conclusion

The economic evaluation showed that atomoxetine is an effective alternative across a range of ADHD populations and offers value-for money in the treatment of ADHD.

Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioural disorder in childhood, affecting over 5% of children worldwide. As well as the core symptoms of inattention, hyperactivity and impulsivity, patients often exhibit learning difficulties and impairment in social functioning. The frequency of referral is higher for boys than for girls (about 2:1), and girls are generally older at the time of referral.

Pharmacological therapy is considered the first-line treatment for patients with severe ADHD and severe impairment. Stimulant medications are licensed in the UK for the management of ADHD in school-age children and young people, and are effective in controlling ADHD symptoms.

While immediate-release preparations of methylphenidate (MPH) have proven effective in the treatment of ADHD, there are a number of problems associated with their use, most notably compliance, stigma and medication diversion. Modified release preparations are now available that overcome the need for multiple daily dosing, and which offer different MPH release profiles, thereby enabling the physician to match the medication to the patient's particular requirements.

This review describes the diagnosis, referral and treatment pathways for patients with ADHD in the UK and the practical considerations when initiating pharmacological treatment. The clinical experience of treating ADHD with a modified-release MPH preparation (Equasym XL®) is illustrated with case studies.

Background

The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study.

Methods

Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo.

Results

The methodology for the ACTION study has been detailed.

Conclusions

The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment.

Trial registration

Australian and New Zealand Clinical Trials Registry ANZCTRN12607000535471.

Objective. Attention-deficit hyperactivity disorder (ADHD) is a developmental disorder characterized by a long-standing pattern of impulsive behavior, hyperkinesia, and inattention. Psychostimulants, for example, methylphenidate, are the treatment of choice for ADHD both in children, adolescents, and adults. Method. The effect of methylphenidate on sleep structure is not well known. We studied the effect of long-acting methylphenidate on sleep in adult ADHD patients, in a naturalistic treatment setting, using actigraphic and polysomnographic recordings. Results. One of our patients experienced manic episode after starting methylphenidate. A wrist-worn accelerometer recording demonstrated a decrease in the duration and quality of sleep. After discontinuation of methylphenidate treatment, the patient's symptoms subsided and there was no need for hospital admission. Actigraphic recording showed a decrease in the amount and quality of the patient's sleep as triggering factor for the manic symptoms. Conclusions. Disruptions of the sleep-wake cycle are probably important etiologic factors in mood disorders, especially bipolar disorder. The changes in length and quality of sleep described in this case report bear close resemblance to those of patients with a manic episode, although these symptoms were induced by methylphenidate.

Tobacco use is more prevalent and smoking cessation less likely among persons with attention deficit hyperactivity disorder (ADHD) than the general population. Evidence that tobacco use and nicotine hold divergent relationships with inattention (IN) and hyperactivity/impulsivity (HI), the core symptoms of ADHD, prompted this post hoc investigation of abstinence patterns by type of ADHD symptoms. Subjects were 583 adult smokers treated openly with bupropion and nicotine patch during the initial eight-week phase of a maintenance treatment study. Using the ADHD Current Symptom Scale, clinically significant ADHD symptom subtypes, i.e., predominantly inattention (ADHD-IN) and predominantly hyperactivity/impulsivity with or without inattention (ADHD-HI+/-IN), were identified. The study outcome was abstinence status, verified by expired carbon monoxide <8 parts per million, at five clinic visits from Week 1 through the end of treatment at Week 8. The distribution by ADHD symptom status was: No ADHD=540; ADHD-IN=20; ADHD-HI+/-IN=23. The study groups did not differ on demographic or smoking variables. The frequency of past major depression was highest with ADHD-IN and the frequency of past alcohol dependence was highest with ADHD-HI+/-IN. Compared to smokers with no ADHD, smokers of both ADHD subtypes combined showed lower abstinence rates throughout the study (OR=0.54, 95% CI: 0.32-0.99). Disaggregation by symptom subtype and separate comparisons against smokers with no ADHD showed that lower odds of quitting occurred mainly with ADHD-HI+/-IN (OR=0.40, 95% CI:=0.19-0.82), not with ADHD-IN (OR=0.74, 95% CI=p=0.36-1.51). Combined bupropion and nicotine patch treatment appears to be helpful for smokers with IN but not smokers with HI symptoms. The reasons for this divergent treatment response warrant further investigation.

Background:

The annual cut-off date of birth for entry to school in British Columbia, Canada, is Dec. 31. Thus, children born in December are typically the youngest in their grade. We sought to determine the influence of relative age within a grade on the diagnosis and pharmacologic treatment of attention-deficit/hyperactivity disorder (ADHD) in children.

Methods:

We conducted a cohort study involving 937 943 children in British Columbia who were 6–12 years of age at any time between Dec. 1, 1997, and Nov. 30, 2008. We calculated the absolute and relative risk of receiving a diagnosis of ADHD and of receiving a prescription for a medication used to treat ADHD (i.e., methylphenidate, dextroamphetamine, mixed amphetamine salts or atomoxetine) for children born in December compared with children born in January.

Results:

Boys who were born in December were 30% more likely (relative risk [RR] 1.30, 95% confidence interval [CI] 1.23–1.37) to receive a diagnosis of ADHD than boys born in January. Girls born in December were 70% more likely (RR 1.70, 95% CI 1.53–1.88) to receive a diagnosis of ADHD than girls born in January. Similarly, boys were 41% more likely (RR 1.41, 95% CI 1.33–1.50) and girls 77% more likely (RR 1.77, 95% CI 1.57–2.00) to be given a prescription for a medication to treat ADHD if they were born in December than if they were born in January.

Interpretation:

The results of our analyses show a relative-age effect in the diagnosis and treatment of ADHD in children aged 6–12 years in British Columbia. These findings raise concerns about the potential harms of overdiagnosis and overprescribing. These harms include adverse effects on sleep, appetite and growth, in addition to increased risk of cardiovascular events.

Attention-deficit hyperactive disorder (ADHD) is a psychiatric illness commonly diagnosed during the early years of childhood. In many adolescents with undiagnosed ADHD, presentation may not be entirely similar to that in younger children. These adolescents pose significant challenges to parents and teachers coping with their disability. Often adolescents with behavioural problems are brought to medical attention as a last resort. This case describes an adolescent who presented to a primary care clinic with school truancy. He was initially treated for depression with oppositional defiant disorder and sibling rivalry. Only following a careful detailed history and further investigations was the diagnosis of ADHD made. He showed a positive improvement with the use of methylphenidate for his ADHD and escitalopram for his depression. The success of his management was further supported by the use of behavioural therapy and parenting interventions. There is a need to increase public awareness of ADHD, especially among parents and teachers so that early intervention can be instituted in these children.

Introduction:

Attention deficit hyperactivity disorder (ADHD) is a neuropsychiatric condition subclassified in DSM-IV according to its core symptoms domains as (a) predominantly inattentive (ADHD-IN), (b) predominantly hyperactive/impulsive (ADHD-H), and (c) combined inattentive and hyperactive/impulsive (ADHD-C). Whether these subtypes represent distinct clinical entities or points on a severity continuum is controversial. Divergence in treatment response is a potential indicator of qualitative heterogeneity. This study examined smoking cessation response by ADHD subtype to osmotic-release oral system methylphenidate (OROS-MPH).

Methods:

Male and female adult smokers (ADHD-C = 167 and ADHD-IN = 87) were randomized to receive OROS-MPH or placebo as augmentation treatment to nicotine patch and counseling. Logistic regression was conducted to test the effect of OROS-MPH versus placebo on prolonged smoking abstinence by ADHD subtype.

Results:

The subtypes were similar in baseline demographic, smoking, and psychiatric history but differed in smoking cessation response to OROS-MPH or placebo as a function of nicotine dependence level. The 3-way interaction was significant; χ2(1) = 8.22, p < .01. Among highly dependent smokers, the prolonged abstinence rates were greater with OROS-MPH than with placebo in the ADHD-C group (60% vs. 31.3%, respectively, p < .05) but higher with placebo than with OROS-MPH in the ADHD-IN group (60% vs. 11.8%, respectively, p < .01). Abstinence rates did not differ by subtype or treatment among smokers who were less nicotine dependent.

Conclusion:

Contrasting treatment response and divergence in the impact of nicotine dependence level support the hypothesis of ADHD subtypes as distinct clinical entities and may indicate the need and directions for personalized targeted treatments of smokers with ADHD.

Objective:

This review examines and summarizes the pharmacodynamic and pharmacokinetic properties, short- and longer-term efficacy, the moderating effect of comorbid disorders, as well as short- and long-term safety and tolerability of atomoxetine for the treatment of pediatric attention-deficit/hyperactivity disorder (ADHD).

Methods:

A systematic literature search was performed to review the extant literature on articles pertaining to the pharmacological treatment with atomoxetine in pediatric and/or adolescent ADHD.

Results:

There is an extensive literature on atomoxetine; over 4000 children have participated in clinical trials of atomoxetine, demonstrating its short- and longer-term efficacy. In addition, studies have examined the moderating effect of comorbid disorders on atomoxetine response, as well as atomoxetine’s therapeutic potential for other psychiatric conditions. Short- and longer-term safety and tolerability continue to be reported.

Conclusions:

Atomoxetine is indicated for both acute and maintenance/extended treatment of pediatric ADHD. Clinicians and families must be familiar with atomoxetine’s evidence base, including its profile of clinical response and its possible effectiveness in the presence of comorbidity.

The persistence of attention deficit hyperactivity disorder (ADHD) into adolescence and adulthood has now been accepted as a clinical entity. The rate of prevalence among adults is assumed to be from 2% to 4%. With increasing age, a symptom change has to be considered; disturbance of attention becomes more prominent, whereas hyperactivity often diminishes or changes to inactivity. Neuroimaging studies show a high striatal dopamine transporter (DAT) availability in most adults with ADHD; this can be reduced by stimulants. Nicotine seems to have a stimulant-like action on the DAT. In most adults with ADHD, therapy has to be multimodal, combining psychotherapy and medication. Methylphenidate is the first-line drug in adult ADHD; further options are amphetamine and noradrenaline reuptake inhibitors. Nonresponders to methylphenidate seem to have no elevated DAT availability prior to therapy. Combination with other psychiatric disorders occurs frequently in adults with ADHD; in these patients additional pharmacological treatment with special regard to the comorbid disease is recommended.

Background

In childhood, attention deficit/hyperactivity disorder (ADHD) is characterized by age-inappropriate levels of inattentiveness/disorganization, hyperactivity/impulsiveness, or a combination thereof. Although the criteria for ADHD are well defined, the long-term consequences in adults and children need to be more comprehensively understood and quantified. We conducted a systematic review evaluating the long-term outcomes (defined as 2 years or more) of ADHD with the goal of identifying long-term outcomes and the impact that any treatment (pharmacological, non-pharmacological, or multimodal) has on ADHD long-term outcomes.

Methods

Studies were identified using predefined search criteria and 12 databases. Studies included were peer-reviewed, primary studies of ADHD long-term outcomes published between January 1980 to December 2010. Inclusion was agreed on by two independent researchers on review of abstracts or full text. Published statistical comparison of outcome results were summarized as poorer than, similar to, or improved versus comparators, and quantified as percentage comparisons of these categories.

Results

Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1) without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2) treatment for ADHD improved long-term outcomes compared with untreated ADHD, although not usually to normal levels. Only English-language papers were searched and databases may have omitted relevant studies.

Conclusions

This systematic review provides a synthesis of studies of ADHD long-term outcomes. Current treatments may reduce the negative impact that untreated ADHD has on life functioning, but does not usually 'normalize' the recipients.

Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in children and adolescents, and in about half of these patients, significant symptomology continues into adulthood. Although impulsivity and hyperactivity are the most salient features of ADHD, cognitive deficits, particularly impairments in attention and executive function, are an important component, particularly in adolescents and adults, with over 90% of adults seeking treatment for ADHD manifesting cognitive dysfunction. Currently available medications treat the core ADHD symptoms but typically do not adequately address cognitive aspects of ADHD, underscoring the need for new therapeutics. Dopamine and norepinephrine are hypothesized to be particularly important in ADHD, but there is emerging evidence that cholinergic neurotransmission, particularly involving neuronal nicotinic acetylcholine receptors (nAChRs), may play a role in the pathophysiology of ADHD. Nicotine has demonstrated procognitive effects in both humans and experimental animals and has produced signals of efficacy in small proof-of-concept adult ADHD trials. Although adverse effects associated with nicotine preclude its development as a therapeutic, a number of novel nAChR agonists with improved safety/tolerability profiles have been discovered. Of these, ABT-418 and ABT-089 have both demonstrated signals of efficacy in adults with ADHD. Notably, tolerability issues that might be expected of a nAChR agonist, such as nausea and emesis, were not observed at efficacious doses of ABT-089. Further understanding of the effects of novel neuronal nAChR agonists on specific aspects of cognitive functioning in ADHD is required to assess the full potential of this approach.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among school-aged children. It is highly symptomatic and associated with significant impairment. This review examines the role of stimulant medications in the treatment of children and adolescents with ADHD. Published clinical studies that compared methylphenidate- and amfetamine-based stimulants in children and adolescents with ADHD support the therapeutic utility of stimulant treatments, and suggest robust efficacy and acceptable safety outcomes in groups treated with either stimulant. Evidence-based guidelines agree that each patient with ADHD is unique and individual treatment strategies that incorporate both drug and non-drug treatment options should be sought. In seeking to optimize individual response and outcomes to stimulant therapy, important considerations include the selection of stimulant class, the choice of long- or short-acting stimulant formulations, addressing effectively any emergent adverse effects and strategies aimed at enhancing adherence to dosing regimen and persistence on therapy.

Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder characterized by atypical levels of inattention, hyperactivity, and impulsivity that impair daily living activities. Although commonly associated with children and adolescents, current literature and practice now demonstrate the impairment the disorder may impose on adults as well. Central nervous system (CNS) stimulant medications are the first-line therapy for ADHD. CNS stimulants include methylphenidate and amphetamine derivatives. Longer-acting formulations used once daily are often preferred to avoid medication administration during school or work as well as to avoid side effects associated with rapid fluctuations in serum concentrations associated with multiple daily dosing. Lisdexamfetamine, a new, novel amphetamine product, has been shown to provide efficacy upwards of 12 hours in children and adults with a side effect profile similar to those of other longer-acting amphetamine products. Owing to its unique prodrug composition and the need for oral administration to activate the medication, lisdexamfetamine may offer advantages in clinical situations where stimulant abuse is a concern.

Background

The objective of this study was to assess the effects of atomoxetine on treating attention-deficit/hyperactivity disorder (ADHD), on reading performance, and on neurocognitive function in youth with ADHD and dyslexia (ADHD+D).

Methods

Patients with ADHD (n = 20) or ADHD+D (n = 36), aged 10-16 years, received open-label atomoxetine for 16 weeks. Data from the ADHD Rating Scale-IV (ADHDRS-IV), Kaufman Test of Educational Achievement (K-TEA), Working Memory Test Battery for Children (WMTB-C), and Life Participation Scale for ADHD-Child Version (LPS-C) were assessed.

Results

Atomoxetine demonstrated significant improvement for both groups on the ADHDRS-IV, LPS-C, and K-TEA reading comprehension standard and composite scores. K-TEA spelling subtest improvement was significant for the ADHD group, whereas the ADHD+D group showed significant reading decoding improvements. Substantial K-TEA reading and spelling subtest age equivalence gains (in months) were achieved for both groups. The WMTB-C central executive score change was significantly greater for the ADHD group. Conversely, the ADHD+D group showed significant phonological loop score enhancement by visit over the ADHD group. Atomoxetine was well tolerated, and commonly reported adverse events were similar to those previously reported.

Conclusions

Atomoxetine reduced ADHD symptoms and improved reading scores in both groups. Conversely, different patterns and magnitude of improvement in working memory component scores existed between ADHD and ADHD+D patients. Though limited by small sample size, group differences in relation to the comparable changes in improvement in ADHD symptoms could suggest that brain systems related to the therapeutic benefit of atomoxetine in reducing ADHD symptoms may be different in individuals with ADHD+D and ADHD without dyslexia.

Trial Registration

Clinical Trial Registry: ClinicalTrials.gov: NCT00191048

Objective

It is not clear whether sibling's gender ratio is associated with attention deficit hyperactivity disorder (ADHD). This study examines whether inattentiveness severity and hyperactivity/impulsivity severity are associated with birth order of children with ADHD.

Method

Participants are a clinical sample of 173 children and adolescents with ADHD and 43 ones without ADHD. Diagnoses were made using Diagnostic and Statistical Manual of Mental Disorders forth edition-Text Revision (DSM-IV-TR), diagnostic criteria according to face-to-face interview with the children and their parents. ADHD DSM-IV checklist was used to measure inattentiveness and hyperactivity/impulsivity scores.

Results

The association of birth order and diagnosis of ADHD was not statistically significant after adjusting for covariate factors. The gender ratio of siblings is not associated with ADHD.

Conclusion

Birth order and siblings gender ratio are independent of ADHD diagnosis. The results of this study support the fact that genetic factors rather than environmental factor of birth order is associated with ADHD. Moreover, contrary to autism, the current results do not suggest the androgen theory for ADHD.

Background

Attention-deficit/hyperactivity disorder (ADHD) is a heritable disorder characterized by symptoms of inattention and/or hyperactivity/impulsivity. Methylphenidate (MPH) has been shown to block the norepinephrine transporter (NET), and genetic investigations have demonstrated that the norepinephrine transporter gene (SLC6A2) is associated with ADHD. The aims of this study were to examine the association of the SLC6A2 -3081(A/T) and G1287A polymorphisms with MPH response in ADHD.

Methods

This study enrolled 112 children and adolescents with ADHD. A response criterion was defined based on the Clinical Global Impression-Improvement (CGI-I) score, and the ADHD Rating Scale-IV (ARS) score was also assessed at baseline and 8 weeks after MPH treatment.

Results

We found that the subjects who had the T allele as one of the alleles (A/T or T/T genotypes) at the -3081(A/T) polymorphism showed a better response to MPH treatment than those with the A/A genotype as measured by the CGI-I. We also found a trend towards a difference in the change of the total ARS scores and hyperactivity/impulsivity subscores between subjects with and without the T allele. No significant association was found between the genotypes of the SLC6A2 G1287A polymorphism and response to ADHD treatment.

Conclusion

Our findings provide evidence for the involvement of the -3081(A/T) polymorphism of SLC6A2 in the modulation of the effectiveness of MPH treatment in ADHD.

The behavioral difficulties of children with attention-deficit/hyperactivity disorder (ADHD) inattentive type differ from those of children with ADHD combined or hyperactive/impulsive type. Existing evidence-based interventions primarily target the disruptive and impulsive behaviors exhibited by children with ADHD combined and hyperactive/impulsive type. A number of recent advances have been made in the non-pharmacological treatment of behavioral difficulties associated with ADHD inattentive type. Additional research using randomized controlled research designs and long-term follow-up evaluation is necessary before these interventions may be considered established evidence-based interventions for patients with ADHD inattentive type.

The Attention Deficit Hyperactivity Disorder (ADHD) symptom presentation of young adolescents with ADHD was examined in association with the transition to middle school. The current study used data collected in the Multimodal Treatment Study of ADHD which included children between 7–9 years of age with a diagnosis of ADHD (n=258) and grade and sex matched controls (n=112). The trajectory of ADHD symptoms before, during and after the transition to middle school was modeled using hierarchical linear modeling. A clear developmental reduction in ADHD symptomatology was observed for all three ADHD symptom domains. For young adolescents with ADHD, the transition to middle school was associated with a disruption in the developmental decline of inattention, hyperactivity and impulsivity symptoms as measured by parent ratings. This effect was also observed for teacher ratings of inattention and hyperactivity. These results support the assertion that the environmental changes associated with transitioning to middle school coincide with a transient reversal in ADHD symptom decline among children with ADHD.

Background

This study examined augmenting atomoxetine with extended-release methylphenidate in children whose attention-deficit/hyperactivity disorder (ADHD) previously failed to respond adequately to stimulant medication.

Methods

Children with ADHD and prior stimulant treatment (N = 25) received atomoxetine (1.2 mg/kg/day) plus placebo. After 4 weeks, patients who were responders (n = 4) were continued on atomoxetine/placebo while remaining patients were randomly assigned to either methylphenidate (ATX/MPH) (1.1 mg/kg/day) or placebo augmentation (ATX/PB) for another 6 weeks. Patients and sites were blind to timing of active augmentation. Safety measures included vital signs, weight, and adverse events. Efficacy was assessed by ADHD rating scales.

Results

Categorical increases in vital signs occurred for 5 patients (3 patients in ATX/MPH, 2 patients in ATX/PBO). Sixteen percent discontinued the study due to AE, but no difference between augmentation groups. Atomoxetine treatment was efficacious on outcome measures (P ≤ .001), but methylphenidate did not enhance response.

Conclusion

Methylphenidate appears to be safely combined with atomoxetine, but conclusions limited by small sample. With atomoxetine treatment, 43% of patients achieved normalization on ADHD ratings.