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ADHD into Adolescence

In ADHD, ADHD child/adolescent, ADHD stimulant treatment, Medication, Neuropsychology, School Psychology on Friday, 14 September 2012 at 05:26

Adolescent ADHD: Diagnosis and Initial Treatment

Scott H. Kollins, PhD

http://www.medscape.org/viewarticle/749104_2

ADHD Into Adolescence

Longitudinal studies demonstrate that ADHD is a disorder that children do not simply outgrow as they reach adolescence.[1-5] Follow-up studies of children with ADHD estimate that the diagnosis persists in 50% to 80% of cases.[1,6-10] Studies of clinically referred adolescents with ADHD also indicate that the disorder continues into adolescence and is associated with various functional impairments, particularly when compared with nondiagnosed peers, including social competence, behavioral and emotional adjustment, school performance, and general quality of life.[11,12]

Although ADHD as a disorder is continuous from childhood into adolescence,[13] the persistence of ADHD into adolescence needs to be considered in the context of adolescence as a period of development in which there are many changes at multiple levels, including physical, psychological, and social changes. During this developmental period, adolescents typically experience a growing influence of peers and independence from family members.[14] For adolescents with a disorder like ADHD in which social and emotional impairment is common,[15] this transitional period may be particularly difficult. Cognitive demands increase along with greater independence from adult supervision (eg, multiple teachers with different teaching styles, amount and scope of homework) as children enter into middle and high school,[11] which requires greater self-regulation, a quality that is often impaired in those with ADHD.

Neuronal and hormonal developmental changes during adolescence can further influence how symptoms are expressed.[14] Related to these biologically based changes, adolescence also is a critical period neurobiologically, with more risk-taking behavior and drug and alcohol use, which correspond with notable changes in motivational and reward-related brain regions. Such behaviors can be problematic because adolescents are naturally more sensitive to the positive rewarding properties of various drugs and natural stimuli and less sensitive to the aversive properties of these stimuli.[16] These behavioral and neurobiological developmental changes in concert with social, hormonal, and physiological changes place adolescents at high risk for substance use.[17,18] ADHD is an additional risk factor for such substance use behavior (reviewed in greater detail below) and thus places adolescents with ADHD at greater risk during this critical developmental period.

Given such developmental changes, the presentation of ADHD changes in adolescence as well, including symptom presentation; although inattentive symptoms continue to be involved in the clinical characteristics of most patients, hyperactive symptoms decline in severity for many.[7,19-21] This symptom presentation continues to cause functional impairment in domains typically impaired in childhood, including academics.[22]

Adolescents with ADHD smoke at significantly higher rates than peers without ADHD and start smoking earlier, demonstrate a higher level of nicotine dependence, and have greater difficulty quitting than youth without ADHD. Some studies have estimated that 25% to 75% of adolescents with ADHD meet diagnostic criteria for ODD or CD. Although mood disorders are often seen in adolescents with ADHD, with an incidence of roughly 10% to 20%, they are less common than DBD. ADHD may be evidence of more severe bipolar disease. For example, ADHD is more common in those with childhood-onset bipolar disorder, which suggests that in some cases ADHD may signal an earlier onset, more chronic bipolar disorder.

ADHD and Comorbid Conditions in Adolescence

Comorbidity within populations of adolescents with ADHD is typically the norm rather than the exception. For example, in one clinical sample of patients 6 to 18 years old, more than half met the criteria for at least one comorbid disorder.[23] Disruptive behavior disorders, including ODD and CD, are particularly common.[24] In general population studies, ADHD increases the odds of ODD or CD by 10.7-fold.[25] Some studies have estimated that 25% to 75% of adolescents with ADHD meet the diagnostic criteria for ODD or CD.[14] In another study, ODD was comorbid among 54% to 67% of clinically referred 7- to 15-year-old children with ADHD.[23] In this study, differences in subtypes also emerged. ODD was significantly more common among those with combined and hyperactive-impulsive ADHD subtypes (50.7% and 41.9%, respectively) than with inattentive subtype (20.8%). Such rates are concerning not only because of the characteristics of these comorbid disruptive behavior disorders (eg, delinquency) that are dealt with in adolescence, but also because CD is a precursor to antisocial personality disorder in adulthood. Given that CD is commonly seen in children with ADHD and is a precursor to antisocial personality disorder, it is not surprising that rates of antisocial personality disorder (among additional forms of Axis II psychopathology) are elevated in adults with ADHD.[4,5,10,26,27]

SUDs are also common in adolescents with ADHD. In longitudinal studies of hyperactive children, the risk for SUDs ranges from 12% to 24% into adulthood.[8,10,26] Because adolescence is a time when initial exposure to substances occurs and because adolescence is also a developmental period during which susceptibility to the reinforcing effects of substances is heightened,[16-18] substance use in adolescence is a concern both as an outcome of current use and of continued risk for future use. This risk is further elevated among adolescents with ADHD. Individuals with ADHD engage in experimentation earlier than children without ADHD.[28,29] Although such findings indicate that the relationship between ADHD and SUDs is independent of comorbidity, CD is a strong predictor of risk for SUDs among children with ADHD when they reach adolescence and adulthood.[30-32] In addition, prospective studies indicate that children with ADHD and co-occurring CD or bipolar disorder are at a higher risk for SUDs during adolescence.[33-35]

Adolescents with ADHD smoke at significantly higher rates than peers without ADHD. Prevalence rates range from 10% to 46% for adolescents with ADHD vs 10% to 24% for adolescents without ADHD.[34,36,37] Even among nonclinical patient samples, there is a linear relationship between number of ADHD symptoms, lifetime risk of smoking, and age of onset of regular smoking.[38] Additional studies have demonstrated that youth with ADHD initiate smoking earlier, exhibit a higher level of nicotine dependence, have greater difficulty quitting than youth without ADHD, and are at an increased risk for becoming a regular cigarette smoker.[37,39] In addition, the relationship between ADHD and tobacco use has remained significant as an independent risk factor after accounting for comorbidity, including CD.[40,41]

Mood disorders are also common among adolescents with ADHD.[42] For example, in one study, 21.6% of children 6 to 18 years old who had ADHD also had a depressive disorder.[23] The combination of a major depressive disorder and a comorbid disruptive behavior disorder is a risk factor for suicidal behavior,[43] and both major depressive disorder and disruptive behavior disorder are common comorbidities in those with ADHD. One longitudinal study assessing childhood ADHD reported that the diagnosis of ADHD in children predicted adolescent depression and/or suicide attempts. In addition, female sex, maternal depression, and concurrent symptoms in childhood predicted which children with ADHD were at greatest risk for these outcomes.[44]

Bipolar disorder is another disorder commonly seen in children with ADHD. Studies have estimated that bipolar disorder co-occurs among 10% to 20% of children and adolescents with ADHD.[45-47] Longitudinal studies of hyperactive children indicate a similar prevalence in adulthood,[5,10,26] although another longitudinal study of children with ADHD reported higher rates into adolescence (12%).[48] In some cases, ADHD may be evidence of more severe bipolar disorder. For example, ADHD is more common in cases of childhood-onset bipolar disorder, which suggests that in some cases ADHD may signal an earlier onset, more chronic bipolar disorder.[48] Regarding anxiety disorders, longitudinal studies of hyperactive children do not report significant elevations in comorbid anxiety disorders.[5,10,26] However, anxiety disorders have been reported in 10% to 40% of clinic-referred children and adolescents with ADHD.[23,49-51] Overall, these studies demonstrate that comorbidity is typical among adolescents with ADHD and further complicates its clinical presentation in adolescence. In addition to concerns about prognosis, such comorbidities can easily complicate issues related to assessment.

Assessment of Adolescents With ADHD

An empirically-based assessment of ADHD typically includes structured clinical interviews, standardized questionnaires, and a review of records, all in the context of diagnostic criteria.[14,52] Cognitive test performance may provide additional value when differentiating ADHD subtypes.[53] Although there is diagnostic continuity of ADHD from childhood into adolescence,[13] assessing ADHD during adolescence needs to be considered in the context of complicating factors. One such factor involves comorbidity. Comorbidity is common in adolescents with ADHD, and conditions can co-occur with ADHD or can mimic ADHD symptoms. Regarding the latter, a diminished ability to concentrate can also be a symptom of a major depressive episode, distractibility and being overly talkative can also be symptoms of a manic or hypomanic episode, and restlessness and difficulty concentrating can be symptoms of generalized anxiety disorder or post-traumatic stress disorder.[54] Further, substance use can confound the assessment for ADHD, as alcohol and illicit drug use can create cognitive impairments that are also common in youth with ADHD.[55-57]

An additional factor that emerges in assessments of adolescent ADHD involves reporting source. In childhood ADHD assessments, parents and teachers are the typical reporters.[14] However, adolescents spend more time with peers and less time with parents. Further, in contrast to elementary school, adolescents have multiple teachers who spend less time with them during the school day and thus have fewer opportunities to observe their students’ behavior. Self-report methods can be incorporated into adolescent ADHD assessments as well; however, adolescents with ADHD have a tendency to underreport the severity of their symptoms,[7,58] which should be considered in any assessment. In adolescents with ADHD, concerns about the accuracy of self-report involve not only their account of ADHD symptoms, but of past delinquent behaviors as well. In one study, adolescents and young adults with ADHD were less likely than those without ADHD to report accurately on delinquent behaviors they engaged in 1 year earlier.[59] Such inaccurate reporting of behavior in ADHD is consistent with findings that persons with ADHD have a tendency toward a positive illusory bias view of their behavior[60] and with theories of ADHD that argue that problems with self-awareness emerge from working memory impairments.[61]

Developmental changes in the presentation of ADHD symptoms also have implications for self-report in the assessment of adolescents with ADHD. In particular, the decline in overt hyperactive symptoms into adolescence[7,19,21,22] makes inattentive symptoms more prominent. As a clinical observation, inattentive features common in ADHD may be experienced more subjectively (eg, daydreaming) than more overt hyperactive behaviors (eg, getting out of one’s seat at inappropriate times), thus making self-report more relevant in this age group.

Finally, the appropriateness of diagnostic criteria for ADHD complicates adolescent assessment. Specifically, the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, Text Revision [54] states that symptom onset must have occurred by age 7 to qualify for an ADHD diagnosis. However, studies addressing the empiric basis for this criterion have called it into question and recommend a revision to include childhood onset at or before age 12.[39,62-64] One study assessing the implications of this diagnostic revision in a large longitudinal sample found that the prevalence estimate, correlates, and risk factors of ADHD would not be affected if this new diagnostic criterion were adopted.[65] Thus, although following diagnostic criteria in adolescent ADHD assessments is recommended, incorporating these more recent findings may be crucial in making a diagnosis.

Treatment of ADHD in Adolescence

Relatively less research has been devoted to efficacious treatments for adolescents with ADHD compared with treatments for children with ADHD.[66] Despite diagnostic continuity, given the physical, social, and psychological changes that occur in adolescents with ADHD, it is somewhat difficult to simply extend childhood treatments to this group. ADHD treatments in this age group are likely to require more extensive and costly interventions. Further, treating adolescents is particularly challenging because they are less likely than children to receive mental health services in the first place.[67]

ADHD treatment is focused on symptom management and the reduction of downstream effects of unmanaged ADHD, such as school failure, automobile accidents, and peer rejection.[68] The more complex academic and social demands during adolescence require a management plan that addresses academic needs throughout the school day and into the evening, as well as weekday and weekend activities including driving, athletic and artistic endeavors, and family and peer relationships. Symptom management should be analogous to symptom management for any lifelong condition, such as nearsightedness, diabetes, or asthma. Such comparisons emphasize that ADHD is not the fault of the person with the disorder but rather a neurobiological condition, and making such comparisons may help the teen deal with any stigma associated with a psychiatric disorder.[69]

For children with ADHD, psychoeducation about ADHD, psychopharmacology (primarily stimulants), parent training in behavior management methods, classroom behavioral modification and academic interventions, and special educational placement are the most effective or promising interventions.[68] The empiric literature regarding extending these treatments into adolescence is much less prevalent, however. Thus, although treatment options for adolescent ADHD may be available, not all are equally effective and in many cases well-controlled studies are lacking. However, some treatments for adolescents with ADHD and their families do have empiric support, particularly pharmacotherapy and specific psychosocial treatment approaches.[68,70]

Although the stimulants and nonstimulants used for the treatment of ADHD can cause minor changes in blood pressure and heart rate, most analyses of studies of cardiac events and sudden death in children, youth, and adults with ADHD treated with stimulants have not found a higher incidence of these events in patients without preexisting structural cardiovascular conditions or a family history of sudden death.[71,72] Therefore, only routine assessment of cardiovascular function, similar to screening for participation in school sports, is recommended.

Current guidelines and consensus statements[71,72] do not recommend specialty cardiovascular screening (including routine electrocardiogram) before initiating treatment for ADHD, either with stimulants or nonstimulants. However, because these medications are known to cause small elevations in blood pressure and pulse (in the case of stimulants and atomoxetine) or hypotensive changes (in the case of the alpha-2 agonists), blood pressure and heart rate should be checked before treatment is started and should be monitored regularly at follow-up visits.

Pharmacotherapy

Stimulant medications. Stimulants and noradrenergic agonists are psychotropic treatments approved by the US Food and Drug Administration (FDA) for use in adolescents. Stimulants include methylphenidates and amphetamine compounds; these medications have a long-standing history in the treatment of ADHD and are considered the first-line therapies for ADHD.[73] The 2 classes of stimulants have slightly differing mechanisms of action. Whereas both block the reuptake of dopamine and norepinephrine into the presynaptic neuron and thereby increase neurotransmitter concentrations, amphetamine compounds also increase the release of dopamine from presynaptic cytoplasmic storage vesicles.[74]

Stimulants are effective in approximately 70% of adolescents with ADHD.[75-77] At least 7 randomized controlled trials have been conducted among adolescents with ADHD and all but one support the efficacy of stimulants for ADHD in adolescence.[74] Consistent with findings of diagnostic continuity of ADHD from childhood into adolescence, the efficacy of stimulants (specifically, methylphenidate) is largely equal from childhood into adolescence.[78] In a meta-analysis of children and adolescents comparing the efficacy of the methylphenidates and amphetamine compounds, amphetamine compounds had a small yet statistically significant advantage over a standard-release form of methylphenidate for parent and clinicians ratings of ADHD symptoms and global ratings (but not for teacher ratings).[79] Although stimulants are effective in acutely reducing ADHD symptoms, common medication side effects (eg, decreased appetite) have prompted consideration of other pharmacologic interventions.[80]

Nonstimulant medications. Noradrenergic agonists approved by the FDA for use in children and adolescents with ADHD include guanfacine extended release (XR), clonidine modified release (MR),[81] and atomoxetine. Although the precise mechanism of action for treating ADHD is unclear, these medications likely facilitate dopamine and noradrenaline neurotransmission thought to play a role in the pathophysiology of ADHD.[81,82]

In 2009, guanfacine XR was the first alpha-2 agent to be approved by the FDA for use in the treatment of ADHD in children and adolescents. According to one randomized controlled trial in children and adolescents with ADHD, guanfacine XR performed better than placebo in reducing teacher-rated ADHD symptoms but not parent-rated ADHD symptoms.[83] In several double-blind, placebo-controlled trials involving child and adolescent participants, guanfacine XR performed significantly better than placebo in reducing ADHD symptoms.[84,85] A 2-year, open-label, follow-up study of guanfacine XR in children and adolescents, with or without co-administration of stimulants, demonstrated continued efficacy as that seen in short-term randomized controlled trials.[86] Such findings emerged in a similar study,[87] although the attrition rate in both studies was greater than 75%, limiting generalizability.

Two randomized, double-blind, placebo-controlled studies evaluating the efficacy of clonidine MR in children and adolescents with ADHD have been conducted. One assessed clonidine MR as a monotherapy, and another studied it as an add-on agent in patients on a non-optimal stimulant drug regimen. In both trials, clonidine MR significantly reduced ADHD symptoms from baseline and was well tolerated.[88,89]

Atomoxetine is another noradrenergic agonist approved for use in adolescents with ADHD,[90-92] and it has comparable efficacy with methylphenidate in reducing core ADHD symptoms in children and adolescents.[93] In one randomized, placebo-controlled, dose-response study of atomoxetine in children and adolescents with ADHD, atomoxetine was consistently associated with a significant reduction of ADHD symptoms.[94] Social and family functioning also improved among those taking atomoxetine with statistically significant improvements in measures of ability to meet psychosocial role expectations and parental impact. In a randomized, placebo-controlled study of atomoxetine among children and adolescents with ADHD, atomoxetine-treated participant reductions in ADHD symptoms were superior to those of the placebo treatment group as assessed by investigator, parent, and teacher ratings.[95] Additional trials have demonstrated the efficacy and tolerability of this medication in children and adolescents with ADHD.[96-101] In addition, acute atomoxetine treatment appears to be equally effective and equally tolerated in children and adolescents.[102] Such findings suggest that pharmacologic differences in tolerability or ADHD symptom response are negligible between children and adolescents.

Treatment Discontinuation in Adolescence

When considering pharmacotherapy, one issue relevant to adolescents with ADHD involves treatment discontinuation. The prevalence of prescribing by general practitioners to adolescent patients with ADHD drops significantly.[103] Further, this decline is greater than the reported age-related decline in symptoms, indicating that treatment is prematurely discontinued in many cases when symptoms persist.[104] In one longitudinal study,[105] 48% of children between the ages of 9 and 15 had discontinued ADHD medication. Age was a significant moderator of medication adherence such that adolescents were less likely to continue their medication.[105] Thus, in addition to a need for continued research devoted to effective treatments for adolescents with ADHD,[66] unique barriers to treatment such as premature discontinuation need to be addressed.

Psychosocial Treatments

In terms of psychosocial treatments for adolescents with ADHD, the empiric literature is sparse compared with the literature on pharmacotherapy options. In addition, because of the many developmental and environmental changes that occur during the transition into adolescence, childhood treatments are not easily translated for this age group. Developmental changes with implications for treatment include that adolescents have a greater cognitive capacity for abstraction, they have more behavioral self-awareness, adolescents are undergoing identity formation and have a need for independence, there is peer influence, there is variability in daily school routines, and adolescents are undergoing physiologic changes (eg, development of secondary sex characteristics).[66] Thus, treatment approaches are recommended that include increased involvement of the teenager, behavioral contingencies that involve more opportunities to socialize with peers and exert independence, collaboration with multiple teachers, homework issues (particularly time management and organizational skills), and self-monitoring strategies.[44] Among studies that have considered psychosocial treatments for adolescents with ADHD, family-based and school-based approaches are the most promising.[44,106]

Family-Based Interventions

Three studies have examined family-based interventions. Barkley and colleagues[107] randomly assigned 12- to 18-year-olds to 8 to 10 sessions of behavior management training, problem-solving and communication training, or structural family therapy. All strategies resulted in significant improvement in negative communication, conflict, anger during conflicts, school adjustment, internalizing and externalizing symptoms, and maternal depressive symptoms at post-treatment, and improvements were largely maintained at a 3-month follow-up visit. However, only 5% to 20% in each treatment group demonstrated clinically significant reliable change following treatment.

Another study compared parent behavior management training with parent behavior management training/problem solving and communication therapy.[108] Both treatments resulted in significant improvement in parent-teen conflicts but were not statistically different from each other. Although such group-level analysis and normalization rates supported the efficacy of these treatments, reliable change indices were similar to those reported by Barkley and colleagues.[107]

Another study evaluated behavior management, problem solving, and education groups for parents of adolescents with ADHD.[109] Pretreatment and posttreatment comparisons indicated statistically significant reductions in the frequency and intensity of self-reported parent-adolescent conflict and in parent-reported problem behavior and positive effects on parent skills and confidence.

Although all these studies are promising, they did not produce much clinically significant reliable change or they were limited by methodologic design (ie, lack of a control or alternative treatment group). In terms of clinical implications, multimodal long-term treatment may be useful to assist parents in their interactions with their teens to manage parental and family distress,[110] as opposed to simply reducing ADHD symptom severity.

School-Based Interventions

Academic functioning is one of the most common concerns of parents of adolescents with ADHD.[110] Interventions targeting academic impairment in adolescents with ADHD are promising.[111] One school-based intervention involving directed note taking through group-based didactic and modeling yielded statistically significant improvements in on-task behavior, material comprehension, and daily assignment scores in a sample of adolescents with ADHD.[112] A more comprehensive treatment, called the Challenging Horizons Program,[113] involves after-school academic training incorporating behavioral strategies in a group and individual setting and monthly group parent training. This program has yielded moderate to large effect sizes on parent- and teacher-rated academic functioning and classroom disturbance compared with a community care group among middle school students with ADHD.[114] Although effect sizes were less promising for social functioning, and methodologic design limited the generalizability of these findings (eg, quasi-experimental design, small sample size), a 3-year treatment outcome study of this program indicated cumulative long-term benefits for the treatment group compared with a community care control group for parent ratings of ADHD symptoms and social functioning.[115] However, this latter study did not indicate any academic benefits of the treatment. Single-subject design studies also support the beneficial impact of behavioral techniques (eg, self-monitoring and functional analysis) in improving goal-oriented behavior in the classroom while reducing disruptive behavior among adolescents with ADHD.[116,117] This deserves additional consideration in future research.

A variant of the interventions aimed at academic behavior in adolescents with ADHD is also emerging. The Homework Intervention Program is a behavioral-based parent training program targeting homework in middle school students. In a pilot study of a small sample of middle school students diagnosed with ADHD (n = 11), multiple-baseline design analyses indicated an improvement in parent-reported homework problems and ADHD symptoms, overall grade point average, and teacher-reported productivity.[118]

Overall, comprehensive school-based interventions are promising and, similar to family-based interventions, warrant future research. Psychosocial treatment for adolescents with ADHD is a small, yet developing field of research. Current treatments need to be more thoroughly assessed. For example, social impairment continues into adolescence.[119] Further, social impairment in youth with ADHD increases the risk for substance use and related problems,[120] which demonstrates the need to also target social functioning in adolescent ADHD interventions. Providers also need to consider how to individualize treatment for adolescents with ADHD and the various potential comorbidities that can be present. In addition, treatments that complement existing psychosocial treatment approaches should be considered to target the multidimensional challenges that adolescents with ADHD face.[66] Some potentially complimentary treatments have yielded promising results. For example, attention training in cognitive training programs, mindfulness meditation, and physical exercise to reduce disruptive behaviors have shown potential, although more methodologically rigorous trials are required.[121-123]

Driving and ADHD

In North America, motor vehicle accidents are the leading cause of death among adolescents.[124] Drivers with ADHD are at significantly higher risk for poor driving outcomes, including increased traffic citations (particularly speeding), accidents that are their fault, repeated and more severe accidents, driving-related morbidity, and license suspensions and revocations.[125] Such findings were not better accounted for by comorbidity or intelligence. Given that substance use is not uncommon in persons with ADHD, the risks associated with drug and alcohol use should also be considered.[126] In terms of clinical implications of such findings, stimulant medications have been shown to improve driving performance in drivers with ADHD.[127-129] The method of stimulant delivery is also an important factor. In one study, adolescent drivers with ADHD drove better throughout the day on a driving simulator after taking an extended controlled-release stimulant compared with an immediate-release formulation.[126]

ADHD Pharmacotherapy and Growth

The effects of ADHD medication (especially stimulants) have been an area of considerable debate and controversy. Reviews indicate that treatment with stimulant medication does lead to subsequent delays in height (approximately 1 cm per year during the first 3 years of treatment) and weight.[130,131] These reviews also indicate that the effect of stimulants on growth decline over time, that growth deficits may be dose dependent, that growth suppression effects may not differ between methylphenidate and amphetamine, that stimulant discontinuation may lead to growth normalization, and that ADHD may itself be associated with dysregulated growth.[130,131]

In one longitudinal study, methylphenidate treatment was associated with small yet significant delays in height, weight, and body mass index.[132] Within the ADHD sample, those who had not received prior stimulant therapy and those who entered the study with an above average height, weight, and body mass index were most likely to experience growth deficits while taking stimulants. Further, the impact on all growth indices was most apparent during the first year of treatment and attenuated over time. In another longitudinal study that evaluated the effect of stimulant medication on physical growth, a newly medicated group exhibited reductions in size after 3 years of treatment relative to a nonmedicated group; the newly medicated group was 2.0 cm shorter and weighed 2.7 kg less.[133]

These findings indicate that in clinical settings, the potential benefits in symptom reduction and daily functioning need to be contrasted with the small but significant effects of pharmacotherapy (particularly stimulants) on growth. In most cases, growth suppression effects do not appear to be a clinical concern for most children treated with stimulants.[130] Although future studies are required to clarify the effects of continuous pharmacotherapy into adulthood to attain a better perspective of the long-term impact on growth, these findings suggest that growth rate should be monitored during treatment for ADHD.

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