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.     

Attention-deficit hyperactivity disorder in girls: epidemiology and management

Attention-deficit hyperactivity disorder (ADHD) in girls is a topic of growing research and clinical interest. For many years, girls with ADHD have been ignored and overshadowed by hyperkinetic and impulsive boys, but they are now attracting interest in an effort to understand the similarities and differences in the prevalence, symptoms, familial risk, comorbidities and treatment of ADHD in the two sexes. A review of past and current literature finds that the symptoms of ADHD are not sex specific, but that identification of girls with ADHD is hampered by parental and teacher bias, and confusion. Girls are more likely to be inattentive without being hyperactive or impulsive, compared with boys. Girls and boys share the same familial risk patterns, as well as similar, although not identical, comorbidity or impairment patterns. The risk of non-treatment is as great in girls as it is in boys; up to 70-80% of identified children will have persistent symptoms and impairment that extends into adolescence and adulthood. Treatment modalities are equally effective in girls and boys. Stimulants, non-stimulants and behavioural modalities are the mainstays of effective treatment.     

ADHD,stimulant treatment in childhood and subsequent substance abuse in adulthood — A naturalistic long-term follow-up study

The purpose of the study was to estimate the risk of substance use disorder (SUD) and alcohol abuse in adulthood among children and adolescents with attention-deficit hyperactivity disorder (ADHD) compared to the background population. Furthermore, to examine whether the age at initiation and duration of stimulant treatment in childhood predicts SUD and alcohol abuse in adulthood. 208 youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of SUD and alcohol abuse were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of SUD and alcohol abuse for cases with ADHD, compared to the background population was 7.7 (4.3–13.9) and 5.2 (2.9–9.4), respectively. Female gender, conduct disorder in childhood and older age at initiation of stimulant treatment increased the risk of later SUD and alcohol abuse. Our results warrant increased focus on the possibly increased risk of substance abuse in females with ADHD compared to males with ADHD.     

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.     

Economic implications of attention-deficit hyperactivity disorder for healthcare systems

Attention-deficit hyperactivity disorder (ADHD) is one of the most common chronic conditions of childhood, with adverse consequences that persist through adolescence into adulthood. Thus, the burden of illness associated with ADHD is high for affected individuals, their families, and society at large. This article reviews available information about ADHD-associated utilisation of healthcare resources, direct medical costs, and the costs or cost effectiveness of pharmacological interventions. Published estimates suggest that direct medical costs for youth with ADHD are approximately double those for youth without ADHD. Cross-sectional studies suggest that ADHD-associated incremental costs are highest for mental health services and pharmaceutical costs, and are greatest for youth with comorbid psychiatric conditions and for those being treated with stimulant medication. To guide relevant clinical and health policy, additional research is warranted on the following: source of increased costs observed among persons with ADHD; patient characteristics of those accruing high medical costs; and the long-term effect of ADHD treatment on direct and indirect costs.     

Compliance with stimulants for attention-deficit/hyperactivity disorder: issues and approaches for improvement

Attention-deficit/hyperactivity disorder (ADHD) affects approximately 8-10% of school-aged children in the US and for many individuals persists into adolescence and adulthood. Both pharmacological and nonpharmacological (behavioural) therapies are used to treat individuals with ADHD. Treatment with stimulant medications, which include methylphenidate and amphetamine, typically requires multiple daily doses to maintain efficacy. The frequency of treatment, coupled with the importance of timing of doses and the long-term nature of treatment, make noncompliance a particular issue in the treatment of ADHD. Studies report noncompliance rates of 20-65% with stimulant treatment, although there are only limited published studies and these show considerable individual variation. Noncompliance can arise through inadequate supervision of those receiving medication, leading to delayed or missed doses, or through the reluctance of individuals to take medication, which is influenced by a number of factors (e.g. social attitudes, pressures or worries surrounding medication use and the inconvenience of multiple daily doses). Two approaches are likely to increase compliance with stimulant treatment: effective once-daily formulations of medication and improved treatment information. The development of effective once-daily formulations for stimulant treatments removes the need for multiple daily doses, with the associated problems of ensuring adequate treatment supervision and personal privacy. Improved provision of education and information for individuals with ADHD, as well as their families and teachers, should help them address the issues surrounding stimulant medication and allow full participation in the treatment process. Together, these strategies should improve treatment compliance for individuals with ADHD.     

A Prospective Examination of the Association of Stimulant Medication History and Drug Use Outcomes among Community Samples of ADHD Youths

A continuing debate in the child psychopathology literature is the extent to which pharmacotherapy for children with attention-deficit/hyperactivity disorder (ADHD), in particular stimulant treatment, confers a risk of subsequent drug abuse. If stimulant treatment for ADHD contributes to drug abuse, then the risk versus therapeutic benefits of such treatment is greatly affected. We have prospectively followed an ADHD sample (N = 149; 81% males) for approximately 15 years, beginning at childhood (ages 8 to 10 years) and continuing until the sample has reached young adulthood (ages 22 to 24 years). The sample was originally recruited via an epidemiologically derived community procedure, and all youths were diagnosed with ADHD during childhood. We report on the association of childhood psychostimulant medication and subsequent substance use disorders and tobacco use. The substance use outcomes were based on data collected at three time points when the sample was in late adolescence and young adulthood (age range approximately 18 to 22 years old). We did not find evidence to support that childhood treatment with stimulant medication, including the course of stimulant medication, was associated with any change in risk for adolescent or young adulthood substance use disorders and tobacco use. These results from a community-based sample extend the growing body of literature based on clinically derived samples indicating that stimulant treatment does not create a significant risk for subsequent substance use disorders.     

A Prospective Examination of the Association of Stimulant Medication History and Drug Use Outcomes among Community Samples of ADHD Youths

A continuing debate in the child psychopathology literature is the extent to which pharmacotherapy for children with attention-deficit/hyperactivity disorder (ADHD), in particular stimulant treatment, confers a risk of subsequent drug abuse. If stimulant treatment for ADHD contributes to drug abuse, then the risk versus therapeutic benefits of such treatment is greatly affected. We have prospectively followed an ADHD sample (N = 149; 81% males) for approximately 15 years, beginning at childhood (ages 8 to 10 years) and continuing until the sample has reached young adulthood (ages 22 to 24 years). The sample was originally recruited via an epidemiologically derived community procedure, and all youths were diagnosed with ADHD during childhood. We report on the association of childhood psychostimulant medication and subsequent substance use disorders and tobacco use. The substance use outcomes were based on data collected at three time points when the sample was in late adolescence and young adulthood (age range approximately 18 to 22 years old). We did not find evidence to support that childhood treatment with stimulant medication, including the course of stimulant medication, was associated with any change in risk for adolescent or young adulthood substance use disorders and tobacco use. These results from a community-based sample extend the growing body of literature based on clinically derived samples indicating that stimulant treatment does not create a significant risk for subsequent substance use disorders.     

Distal forearm fractures in New Zealand children: annual rates in a geographically defined area

AIMS: To estimate the annual incidence of distal forearm fractures in New Zealand children and to describe circumstances associated with this fracture. METHODS: The ages and dates of fracture of all girls and boys aged three to fifteen years with distal forearm fractures treated at Fracture Clinic, Dunedin Public Hospital in one calendar year were recorded. RESULTS: The age-standardised annual incidence rates for Dunedin girls and boys aged three to fifteen years were 10.4 per 1000 (95% CI 8.3-12.4 per 1000), and 10.4 per 1000 (95% CI 8.3-12.6 per 1000), respectively. The peak incidence in girls was observed at ten years of age (23.5 fractures per 1000) and for boys at thirteen years of age (25.3 fractures per 1000). Extrapolation of these rates to all New Zealand suggest that in children aged three to fifteen years, 3659 (95% CI 2906-4413) distal forearm fractures occur per year in girls, and 3845 (95% CI 3087-4603) per year in boys, representing about 20 fractures per day. Many of the fractures for the girls and boys resulted from apparently slight trauma (62.2% and 61.6%, respectively). CONCLUSIONS: Distal forearm fractures are very common events in New Zealand children and adolescents, and are usually caused by apparently slight trauma.     

Childhood attention deficit hyperactivity disorder and the development of substance use disorders: Valid concern or exaggeration?

Attention deficit hyperactivity disorder (ADHD) is a common childhood disorder associated with many behavioral problems in adolescence and adulthood. In particular, researchers have identified comorbid substance use disorders in many adolescents and young adults who were diagnosed with ADHD as children. Conflicting reports exist regarding the developmental risk for substance use problems and disorders in these individuals. This paper reviews the recent literature evaluating the relationship between childhood ADHD and substance use. Research suggests that in the absence of conduct disorder, ADHD carries only a moderate risk for subsequent substance use. Degree of risk appears to be related to specific drugs of abuse and particular ADHD symptoms. Additionally, whether stimulant treatment of ADHD symptoms predisposes children to later substance use is an important concern. Currently, little evidence exists to support this notion and most research suggests that stimulant treatment serves as a protective factor for substance use. ADHD is an important precursor to subsequent disorders in children and further research is necessary to diminish the risk for substance use in this population.     

Effect of comorbid symptoms of oppositional defiant disorder on responses to atomoxetine in children with ADHD: a meta-analysis of controlled clinical trial data

Rationale Up to 60% of children with attention-deficit/hyperactivity disorder (ADHD) suffer from comorbid affective or behavioral impairments, the most common condition being oppositional defiant disorder (ODD), which occurs in 40–60% of children with ADHD.Objectives This post hoc meta-analysis was performed to determine the effect of the presence of comorbid ODD symptoms on clinical outcomes among pediatric and adolescent subjects being treated for ADHD.Methods Acute-phase data were analyzed from three randomized, double-blind, placebo-controlled studies in outpatients aged 6–16 and meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, criteria for ADHD. Subjects received placebo or atomoxetine (max 1.8 mg/kg/day, daily) for 6–8 weeks. Patients were diagnosed with comorbid ODD on structured diagnostic interview (Schedule for Affective Disorders and Schizophrenia for School-aged Children—Present and Lifetime Versions).Results Of the 512 subjects studied, 158 were diagnosed with comorbid ODD. Relative to placebo, atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects irrespective of the comorbidity with ODD. ADHD subjects also showed significant improvements from baseline on most of the psychosocial measures of the child health questionnaire irrespective of the comorbidity with ODD. Reduction in ODD symptoms was highly related to the magnitude of ADHD response.Conclusions Atomoxetine treatment significantly reduced ADHD symptoms in both ODD-comorbid and noncomorbid subjects to similar extents, indicating that the presence of comorbid symptoms of oppositionality does not affect clinical outcomes of treatment of ADHD with atomoxetine.     

Predictive factors for more than 3 years' duration of central stimulant treatment in adult attention-deficit/hyperactivity disorder: a retrospective, naturalistic study

ABSTRACT: There is effective short-term central stimulant (CS) treatment of attention-deficit/hyperactivity disorder (ADHD) symptoms in adult ADHD, and despite this, many patients discontinue the treatment too early. The present study examines the duration of CS treatment in a Norwegian cohort of adult ADHD to identify predictors for long treatment duration (≥3 years).The data were based on the medical records of a sample of 117 of all 119 adult ADHD patients diagnosed over a period of 8 years in a specific catchment area and treated with CS. A logistic regression model was applied to identify possible predictors for long treatment duration.The sample was severely impaired in terms of comorbidity, educational achievement, and employment. The median duration of CS treatment was 33.0 months. Use of extended-release formulations of methylphenidate predicted long treatment duration positively (odds ratio, 4.420 [95% CI, 1.875-10.419]), whereas baseline antisocial personality disorder predicted long treatment duration negatively (odds ratio, 0.210 [0.085-0.518]).This study showed that it is possible to treat severely impaired and highly comorbid adult ADHD patients with CS over years. The finding that extended-release formulations of methylphenidate predict long treatment duration supports previous research, and it is important to show this association in naturalistic samples such as in the present study. Comorbid antisocial personality disorder was a negative predictor of long CS treatment duration. Univariate analyses also indicate that comorbid substance use disorder is related to shorter duration of CS treatment.     

Attention-deficit hyperactivity disorder

The epidemiology, etiology, pathogenesis, clinical presentation, diagnostic criteria, and clinical course of attention-deficit hyperactivity disorder (ADHD) are described and the role of pharmacotherapy in the management of this disorder is discussed. ADHD is a behavioral disorder of unknown etiology characterized by inattention, impulsiveness, and hyperactivity. The behavior, which may be manifest at home, at school, or in social situations, is generally worse in settings requiring sustained attention; as a result, academic underachievement is frequently an associated problem. Although the onset usually occurs before the age of four years, ADHD is most commonly diagnosed when the child enters school. It is up to six times more common in boys than in girls. Nearly one third of all children with ADHD continue to show symptoms of the disorder in adulthood. While many questions about the pathophysiology of ADHD remain unanswered and a cure has not yet been found, pharmacotherapy can effectively control the symptoms of the disorder in most patients. Three psychostimulant medications--dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline--are considered the drugs of first choice for management of the behavioral manifestations of ADHD. Dextroamphetamine and methylphenidate are equally effective in improving the symptoms of ADHD. Pemoline, a newer agent, may be tried in patients who cannot tolerate or do not respond to these two first-line agents. Common adverse effects associated with stimulant medications include anorexia, insomnia, stomach pain, and weight loss; these are generally transient and decrease with time. Imipramine hydrochloride and desipramine hydrochloride are less effective and may produce more serious adverse effects than the psychostimulants and are therefore considered second-line agents for the treatment of ADHD. Dextroamphetamine sulfate, methylphenidate hydrochloride, and pemoline have been shown to effectively control the behavioral symptoms of ADHD. For maximum impact, pharmacotherapy should be accompanied by behavioral, educational, and psychosocial intervention.     

可乐定治疗共患注意缺陷多动障碍的抽动障碍患儿的临床疗效

目的:探讨可乐定治疗共患注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)的抽动障碍(tic disorder,TD)患儿的临床疗效。方法:对符合美国精神障碍诊断与统计手册第4版(DSM-IV)中TD和ADHD标准的儿童予系统的可乐定治疗,逐渐调整至目标剂量,并维持治疗12周。以耶鲁综合抽动严重程度量表(YGTSS)评定抽动症状;根据家长填写的ADHD评定量表(ADHD-RS-IV)评定注意缺陷多动症状;并观察药物不良反应。结果:本研究完成系统可乐定滴定并维持治疗12周的共患ADHD的TD患儿40例,男36例,女4例;年龄6.50～14.50(9.84±2.90)岁。完成剂量滴定患儿的目标剂量5μg/(kg.d),最大剂量不超过0.2 mg/d。治疗后抽动总分(9.78±7.76)分,运动抽动分(7.52±4.85)分,发声抽动分(2.26±3.27)分,功能受损程度评分(8.50±5.70)分;治疗前抽动总分(21.34±8.66)分,运动抽动分(15.41±4.68)分,发声抽动分(5.93±7.10)分,功能受损程度评分(21.16±11.76)分。治疗后运动抽动及发声抽动的数量、频度、强度和复杂性均较治疗前显著减少(P<0.05)。治疗后ADHD总分(12.63±9.07)分,注意缺陷评分(7.43±4.74)分,多动-冲动评分3.0分;治疗前ADHD总分(31.05±8.51)分,注意缺陷评分(17.55±3.08)分,多动-冲动评分13.0分。治疗后家长ADHD症状评定量表总分及分量表分较治疗前均显著下降(P<0.05)。结论:可乐定治疗共患ADHD的TD患儿的运动抽动、发声抽动、注意力缺陷、多动-冲动均有明显疗效,能改善患儿生活质量。     

Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult

Abstract

Background: The use of the natural product, kratom, has increased significantly in recent years. The active compounds in kratom have been shown to produce both opioid and stimulant-like effects. While kratom is marketed as a safe, non-addictive method to treat pain and opioid withdrawal, there have been reports demonstrating that kratom is physiologically addictive and linked to overdose deaths. A limited number of case-reports are available describing treatment of kratom use disorder in middle-aged adults, generally in the context of chronic pain and in inpatient settings. Our case is unique in that we describe outpatient treatment of kratom use disorder in a young adult with comorbid attention deficit hyperactivity disorder (ADHD) and in the absence of chronic pain. Case: A 20-year-old college student with ADHD presented to an office-based opioid agonist treatment clinic (OBOT) for treatment of kratom use disorder. He was unable to attend inpatient or residential substance use treatment due to work and school obligations. Additionally, he had stopped taking his prescribed stimulant due to cardiac side effects. The OBOT team successfully initiated buprenorphine-naloxone (BUP/NAL) sublingual films via home induction to treat his kratom use disorder. The patient is being monitored monthly with plans to slowly taper his BUP/NAL dose as tolerated. Discussion: We present a case of a young adult male with kratom use disorder, complicated by a diagnosis of ADHD, successfully treated with BUP/NAL via home induction. The patient is currently kratom-free, reports improved mood and sleep patterns since initiating BUP/NAL, and is able to once again tolerate his ADHD stimulant medication. Healthcare providers should be aware of the use of kratom and consider utilizing BUP/NAL to treat dependence to this botanical drug.