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Canadian Paediatric Society

Position statement

ADHD in children and youth: Part 2—Treatment

Posted: Oct 24 2018


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Principal author(s)

Mark E. Feldman, Alice Charach, Stacey A. Bélanger; Canadian Paediatric Society, Mental Health and Developmental Disabilities Committee

Paediatr Child Health 2018, 23(7):462–472.

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder. Three position statements have been developed by the Canadian Paediatric Society, following systematic literature reviews. Statement objectives are to:

1) Summarize the current clinical evidence regarding ADHD,

2) Establish a standard for ADHD care, and

3) Assist Canadian clinicians in making well-informed, evidence-based decisions to enhance care of children and youth with this condition.

Specific topics reviewed in Part 2, which focuses on treatment, include: evidence and context for a range of clinical approaches, combining behavioural and pharmacological interventions to address impairment more effectively, the role of parent and teacher (or other caregiver) training, the use of stimulant and nonstimulant medications, with effects and risks, and dosing and monitoring protocols. Treatment recommendations are based on current guidelines, evidence from the literature, and expert consensus.

Keywords: ADHD; Adverse effects; Combined interventions; Medication management

GUIDE FOR CLINICIANS: Non-pharmacological interventions

A multimodal approach combining behaviour management and pharmacological interventions is often needed to effectively treat children and adolescents impaired by attention-deficit hyperactivity disorder (ADHD). Because ADHD is a chronic condition, an important first step is to develop a shared-care approach with the parents and child or adolescent, based on a shared understanding of identified treatment goals and preferences and accurate information about underlying etiology.

NONPHARMACOLOGICAL INTERVENTIONS FOR ADHD

Current ADHD guidelines recommend including nonpharmacological interventions as part of treatment planning for children and adolescents with ADHD [1][3]. Some evidence-based interventions, such as organizational skills training, have specific indications, while others, such as physical exercise, have a wide range of benefits. Recommendations for nonpharmacological intervention should be individualized, based on specified treatment goals, follow a thorough evaluation of comorbid conditions and be appropriate for the child’s or youth’s age and stage, as well as being both acceptable to and feasible for the patient, family, and schoolteachers. Table 1 summarizes nonpharmacological interventions for ADHD.

INITIATING TREATMENT

For children with ADHD younger than 6 years of age, evidence is robust that first-line intervention should be parent behaviour training [4]. Overall evidence for the effectiveness of psychostimulants is weak, and Health Canada has not approved their use in this age group.

Medication works primarily on core ADHD symptoms and should be considered for children aged 6 years and older [5][7].

Table 1. Nonpharmacological interventions for ADHD (PDF version)
InterventionEvidenceContext for use
PsychoeducationAn RCT comparing a structured psychoeducational intervention with a support group for parents of children and youth with ADHD showed improvements in parent-reported symptoms, with additional benefits in prosocial behaviour after 1 year [9].When initiating treatment, providing accurate education and information to patients and families are essential for successful management planning and implementation. Misperceptions are common. Many patients and families rely on both online and physician-recommended resources for information [10].
Shared decision-makingA 6-month longitudinal cohort showed that parents who focused on academic improvements were more likely to initiate medication, while those more concerned with behaviour were likelier to begin behavioural therapy [12].In shared decision-making, all participants (parents, youth/child, and physician) share information regarding diagnosis and treatment before the latter is implemented. Treatment planning is enhanced by identifying goals for improvement [1]: academic performance [2], behavioural compliance [3], interpersonal relationships [11].
PBT

Meta-analytic examination of RCTs of PBT using observations and teacher ratings showed improved parenting skills for conduct problems. Parent ratings showed effectiveness for ADHD symptoms, social skills and academic performance [95].

For preschool age children, PBT should be the intervention of first choice [4].

For disruptive behaviours comorbid with ADHD, initiating PBT before medication proved more effective than medication followed by PBT [96].

Classroom management

Classroom behaviour management strategies have been considered a well-established treatment for ADHD for over a decade [97].Teachers help children with special needs by setting classroom rules and expectations, providing students with individual attention and praise, and offering both direct and indirect messages of acceptance.
Daily report cardAn RCT of daily report cards and psychological consultation showed improved compliance with classroom rules, academic productivity and classroom behaviours [98].Behaviour management strategies that include parent and teacher cooperation have been shown to improve homework completion [98].
Behavioural peer interventionsRCTs of two such programs (different researchers) observed improved peer skills in classroom settings; therefore, the intervention is considered well established [99].Adults use behaviour modification techniques to help children improve peer skills in recreational settings, such as summer camps [99].
Social skills trainingNo clear evidence of efficacy for improved classroom behaviour or peer interaction skills [5]. 
Organizational skills trainingRCTs of two such programs (different researchers) showed improvements in organization, time management and planning; therefore, the intervention is considered well established [100].These programs address specific executive functioning difficulties common in children with ADHD. They are added to other interventions [100].
Cognitive trainingMeta-analysis showed benefit for working memory skills targeted by computerized interventions. Parents, but not teachers, reported improved inattention symptoms [101].Computerized interventions for specific neuropsychological deficits (e.g., working memory) require additional development before they can be considered clinically useful [102].
EEG neurofeedbackSystematic reviews showed benefit reported by parents; benefit from blinded outcomes was less clear [103].Such interventions require additional development before they can be considered clinically useful [104].
DietSmall effects on ADHD symptoms were shown for free fatty acid supplementation and restricted elimination diets (e.g., removing artificial food dyes) [6][105].Children with a suspected dietary deficiency, insufficiency or food allergy should be evaluated [106].
ExerciseMeta-analysis of exercise interventions (e.g., short-term aerobic exercise and yoga) showed improvement in core ADHD symptoms and in related anxiety and cognitive functions [107].Exercise provides additional benefits to health and well-being [108].
ADHD Attention-deficit hyperactivity disorder; EEG Electro-encephalograph; PBT Parent behaviour training; RCT Randomized control trial.

However, more than one-half of children with ADHD have psychiatric and developmental comorbidities [8]. For this reason, nonpharmacological interventions (Table 1) should be considered routinely as part of comprehensive ADHD care, with specific goal-setting to improve compliance, academic performance, and quality of life. Psychoeducation around optimal supportive care should be available for all patients and families of children and youth with ADHD [9][10].

Generally, parents’ preferences for either medication or behavioural interventions for younger children are guided by beliefs and values, which interventions are easily accessible, and concerns about adverse effects (AEs) and stigma [11]. Parents who are focused on improving academic skills are more likely to initiate medication, while those more concerned about behaviour are likelier to choose behavioural therapy [12].

Prescribing stimulants for non-ADHD-related learning or behaviour disorders and polypharmacy for ADHD treatment are growing concerns. Prescription rates for ADHD in the UK have risen over the last 20 years from 0.4% to 4% of children [13]. One study found that more than 10% of children in some districts of the USA were being treated with stimulants [14]. Canadian prescription rates are also reported to be on the rise, and may be approaching US levels [15].

Recommendation 1: Treatment approaches for children and youth with ADHD and comorbidities must be multimodal and part of an individualized, comprehensive care plan. A psychoeducational plan of interventions should be initiated first, combined with other nonpharmacological interventions and medication when indicated, always keeping specific functional or behavioural goals in mind.

Recommendation 2: Medication use should be reserved for children and youth diagnosed with ADHD (see the companion statement on etiology, diagnosis, and comorbidity in this issue) whose learning or academic performance are impaired by attention difficulties or whose behaviours and social interactions are impaired by lack of impulse control and hyperactivity.

EFFECTS OF STIMULANT MEDICATION

Outcomes from well-designed, long-term trials to evaluate the effectiveness of stimulants for ADHD are under-researched [16] and, due to publication bias [17], may also be under-reported. Stimulants appear to improve parent-reported quality of life in children being treated for ADHD [18][21] and are associated with improved academic achievement and lower rates of comorbid anxiety and depression in young adulthood [22]. However, lasting impact on the core symptoms of ADHD has not been confirmed [23].

Short-term randomized control trials of stimulant use for ADHD have shown that these medications can improve function in multiple domains, including decision-making [21], handwriting [24], and school work productivity [25]. Among adolescents and young adults with ADHD, longer-acting preparations of extended-release (ER) stimulants have demonstrated improved evening driving performance [26]. Population-based observational studies have indicated that stimulant treatment is also associated with better math and reading scores [27], fewer injuries leading to emergency room visits [28][29] and reduced morbidity and mortality related to motor vehicle injuries [30].

Long-term cohort studies following children who were diagnosed in childhood with ADHD into adulthood, compared with children living without ADHD, have documented that individuals with ADHD who continue to experience higher rates of inattention, impulsiveness and hyperactivity than their typical peers will also have greater difficulties with educational and occupational adjustments, risky sexual behaviours, and psychiatric disorders than those for whom core ADHD symptoms diminished over time [31][32].

These studies suggest that when ADHD symptoms persist into young adulthood, there is reason to continue stimulant treatment to address them. Indeed population studies show that stimulant use is associated with better employment outcomes [31][32], and reduced morbidity and mortality related to motor vehicle injuries [30].

INITIATING AND MONITORING STIMULANT MEDICATIONS

Initial titration and monitoring to evaluate the benefits and AEs of ADHD medication should include using standardized questionnaires [33][35] and checklists [33][34] (www.cps.ca/en/tools-outils/mental-health-screening-tools-and-rating-scales). Parents and older children can provide baseline observations regarding symptom severity and potential AEs. Baseline and follow-up teacher observations are also essential for monitoring treatment response [36].

Recommendation 3: When initiating treatment with ADHD medication, set goals or target outcomes focused on symptom reduction and improved functioning (e.g., improving family or peer relationships, reducing disruptive behaviours, enhancing independence in self-care or homework) to guide the treatment plan.

Recommendation 4: Use standardized checklists to monitor treatment response. Information must be obtained from two or more settings and include direct input from school.

The differences in efficacy and AE profiles between methylphenidate (MPH) and dextroamphetamine (DEX) stimulant preparations are minimal. Both MPH and DEX are available in short-, medium- and ER formulations. To start, the choice of one stimulant over another depends on duration of effect, cost and ease of administration. Differences in effectiveness or AE profiles among stimulant brands, as experienced by individuals, appear to be idiosyncratic. Switching from one stimulant formulation to another is recommended over switching from a stimulant medication to a nonstimulant. The child’s or youth’s family and physician, with input from teachers and caregivers, can usually determine whether a specific psychostimulant and dose is effective and well-tolerated within 2 to 4 weeks of initiation.

Recommendation 5: Initiate treatment with a stimulant formulation from either the MPH or DEX subclass. Switching to another formulation within the same subclass or within the other subclass should be tried before concluding that a child or youth does not respond to or cannot tolerate stimulants.

Choosing initially between ER versus immediate release (IR) stimulant preparations

Medication adherence correlates better with once-daily ER prescriptions than with short-acting prescriptions [37][43]. AEs are a common reason for discontinuing stimulant medications [44]. Finding the optimal dose within a relatively short time improves adherence because poor adherence is correlated with dosing that is too low for too long [45] or with high dosing that causes unacceptable side effects [44][46]. Lower medication adherence is also associated with older age and with having a learning, mood or behavioural comorbidity [40][43]. Unfortunately, ER preparations are prohibitively expensive for many families [46].

Recommendation 6: In combination with nonpharmacological interventions, ER stimulants are recommended as first-line therapy for most children and youth with ADHD.

The occasional use of IR formulations may be indicated for children who cannot yet tolerate ER stimulants (e.g., because they are preschool-age) or for individuals with short-term attention and behavioural targets.

Longer-acting ER formulations are especially appropriate for older children whose homework demands protracted attention or for individuals experiencing impulsive or at-risk behaviours or difficulties with peer and family relationships outside of school hours. Continuing ER medication use over weekends and holidays may benefit children or youth with ADHD who are at high risk for poor outcomes, engaged in risk-taking behaviours or struggling with peer interactions. In these circumstances, ‘drug holidays’ should not be recommended routinely, unless there are specific concerns about a medication’s AEs. Dosing and duration become particularly important medication features for adolescents, who may drive during evening hours or at night [26]. An additional benefit of ER medications is that they are less likely to be diverted for recreational use [47][48] than IR-stimulants because ER capsules are difficult to crush, effectively prohibiting intranasal or intravenous administration. Also, the controlled rate of release minimizes rapid absorption and delivery to the brain [49][51].

The duration of action of ER stimulants can range between 6 and 13 hours (Table 2). A single dose of any ER stimulant is usually given at breakfast time. Administered more than 30 minutes before breakfast, an ER stimulant can diminish appetite for breakfast. Appetite suppression is the most commonly reported AE with stimulant use. Although appetite suppression may be acceptable at lunchtime, it should no longer be present by dinnertime. Titration should aim for medication to ‘wear off ’ to avoid dinnertime appetite suppression and sleep problems.

Dosing should be individualized based on response to careful titration to the lowest effective dose, not on severity of presentation or (solely) on the child or youth’s age or size. Close monitoring is essential until medication effectiveness and tolerability have been optimized. When the initial dose is tolerated but not effective, small increments at weekly, biweekly or monthly intervals may be helpful, until symptoms are improved or AEs appear.

Dosing requirements may need to be increased initially because of ‘up-regulation’ of the liver enzymes that catabolize stimulants, which causes tachyphylaxis [47]. When dosage response has been optimized, monitoring every few months helps ensure the dose remains appropriate and can be adjusted as necessary.

Dose adjustments must be closely tied to reports of benefits or AEs from families and teachers. Clinicians must remember that preconceived notions concerning stimulants persist in the popular mind and sometimes colour perceptions of treatment effectiveness [52][54]. Moreover, the different natures of home and school settings and the duration of medication action can sometimes cause or enhance true differences in functioning between school and home. For example, when teachers report improvements not observed by parents, the duration of medication action may be limiting observable benefits to school hours. When caregivers report benefits that are not seen by teachers, be sure to consider a comorbid learning difficulty, bullying or the placebo effect. When parents and teachers both report inadequate response to a medication, despite counselling, trials of more than one medication and careful dose titration, revisit the original diagnosis.

If medication requirements appear to exceed maximum recommended doses (Table 2), consulting with an expert in ADHD management is essential.

Monitoring the AEs of stimulant medications

There is significant variability among individual dosing requirements and dose-related AEs. Before initiating any medication, it is important to determine baseline symptom rates, specifically for low appetite, sleep difficulties, moodiness, irritability, and tics, as these are among the most common AEs of stimulant medications but are also common symptoms in untreated children and youth with ADHD.

Table 2. Stimulant and nonstimulant medications for ADHD
ER methylphenidate formulationDuration of action (hours)*

Mechanism of sustained action

Palatability considerations

Starting dose | Range | MaximumNotes
Concerta (OROS-MPH)8–12 hOsmotic release in multiple stagesCapsule must be swallowed whole0.5 mg/kg | 0.8 mg/kg to 1.5 mg/kg | 2 mg/kg or 72 mgMay be a suitable first choice for older children (see duration of action and palatability considerations)
Biphentin (MPH-HCl, controlled release capsules)6–10 hEnteric coating of minute ‘beads’ within capsule

Beads can be sprinkled on a spoon of soft food (must not be chewed)

0.5 mg/kg | 0.8 mg/kg to 1.5 mg/kg | 2 mg/kg or 80 mg

May be a suitable first choice for younger children (see duration of action and palatability considerations)

ER methylphenidate formulation

Duration of action (hours)*

Mechanism of sustained action

Palatability considerations

Starting dose | Range | Maximum

Notes

Generic MPH ER4–5 h (varies widely)Compressed powderIntended to be swallowed whole

0.5 mg/kg | 0.8 to 1.5 mg/kg | 2 mg/kg or 72 mg (in two divided doses, with second dose at lunch)

Duration may be too short for full-day, single-dose Rx
Ritalin SR4–5 h (varies widely)Compressed powderIntended to be swallowed whole

0.5 mg/kg | 0.8 to 1.5 mg/kg | 2 mg/kg or 60 mg (in two divided doses, with second dose at lunch)

Duration may be too short for a full-day single-dose Rx

Amphetamine/ Dextroamphetamine

Duration of action (hours)*Mechanism of sustained actionPalatability considerations

Starting dose | Range | Maximum

Notes

Vyvanse

Lisdexamphetamine dimesylate

8 to 13 h‘Pro-drug’ only bioavailable after slow enzymatic cleavage of lysine from dexamphetamine

Capsule contains powder and may be mixed with food or drink

0.5 mg/kg | 0.8 mg/kg to 1.5 mg/kg | 2  mg/kg or 80 mg

May be a suitable first choice for older children (see duration of action considerations)

May also be suitable choice for younger children (see palatability considerations)

Adderall XR

Mixed amphetamine salts

6–8 hEnteric coating of minute ‘beads’ within capsule

Beads can be sprinkled on a spoon of soft food (must not be chewed)

0.25 mg/kg | 0.4 mg/kg to 0.7mg/kg | 1 mg/kg or 30 mg

May be suitable choice for younger children (see duration of action and palatability considerations)

Dexedrine spansule4–6 h

Spansule with sustained-release capsule

Spansule to be swallowed whole (must not be crushed or chewed)10 mg taken daily | range 20 mg to 30 mg per day | maximum 40 mgDuration may be too short for a full-day single-dose Rx

Nonstimulant formulation

Duration of action (hours*, varies widely)

Mechanism of sustained action

Palatability considerations

Starting dose | Range | Maximum

Notes
Strattera (Atomoxetine HCl)24 h

Selective norepinephrine reuptake inhibitor

Capsule should be swallowed whole and not opened

0.5 mg/kg/d | 40 mg per day

0.5 mg/kg/d to 1.2 mg/kg/d

Increase by 0.3 mg/kg intervals every 1–2 weeks

Maximum dose: 80 mg or 1.2 mg/kg/d

No additional benefit has been demonstrated at doses greater than 1.2 mg/kg/d

Clinical response is gradual.

Usually assessable by 4 weeks, but can take up to 3 months after starting treatment.

Once-daily dosing is common.

Limited data suggest that twice daily dosing improves tolerability and efficacy.

Intuniv XR (Guanfacine XR)24 h

Selective alpha 2a-adrenergic receptor agonist

Matrix tablet to be swallowed whole once daily

1 mg/d | 0.05 mg/kg/d to 0.12 mg/kg/d, in AM or PM |

At 6–17 years old: 4 mg/day MAXIMUM, in combination with stimulants

At 6–12 years old: 4 mg/day MAXIMUM monotherapy

At 13–17 years old: 7 mg/day MAXIMUM monotherapy

Danger of rebound hypertension when stopped abruptly

To discontinue, taper the dose in decrements of 1 mg every 3 to 7 days.

Data adapted from ref. [109]*.

ER Extended-release; Rx Prescription; SR Sustained-release

Duration of action is highly variable and may be shorter or longer than indicated for certain individuals.

Another concern commonly expressed by families is that a child or youth seems ‘too quiet’ or over-focused when their medication dose is too high. Some adolescents also describe personality changes or feeling constricted. Preschool children experience higher rates of side effects, especially irritability and moodiness, and, typically, better tolerate smaller doses of stimulant medications [55]. At typical doses, the overall risk for developing or exacerbating a tic disorder is not increased in children with ADHD who are treated with stimulants, compared with untreated children [56][59]. Transient fluctuations in tic severity are common, particularly with stress. Tics should be monitored and may require dose adjustments without discontinuing the medication. A comorbid tic disorder is not a contraindication for ADHD treatment.

Psychostimulants and nonstimulants are associated with a variety of peripheral vasculopathic symptoms, including Raynaud’s phenomenon [60]. Symptoms are often triggered months or years after starting these medications, by a change of dose or drug [61][62].

Only rarely has psychosis been noted as an AE of stimulants [63]. Priapism has been reported, again rarely, in individuals with ADHD who are taking stimulants [64], but is also observed in unmedicated individuals with ADHD [65]. Until more evidence is available, families should be counselled about possible risks and management.

Cardiovascular changes with stimulants include slight increases in heart rate and blood pressure. However, the presence of abnormal blood pressure (i.e., in the hypertensive or prehypertensive range) does not appear to differ significantly in youth with ADHD who are taking a stimulant compared with those who are not [66]. Although there is no clear consensus among experts, the product monographs for stimulants recommend monitoring blood pressure at appropriate intervals, especially in individuals with hypertension. In children or youth with ADHD being treated with stimulants, risk for developing a dysrhythmia is not significantly increased [67]. Routine pretreatment ECG screening is not recommended. A careful history and physical examination to assess risk factors [68] should be completed before initiating treatment with a stimulant medication.

Recommendation 7: Only children and youth at risk for stimulant-induced cardiovascular AEs (based on family history or a personal history/cardiac examination) should undergo ECG testing or a paediatric cardiology consultation before treatment with stimulants is initiated [68].

Special considerations regarding appetite, growth, and stimulant medication

One recent study has suggested that a diminution in growth of approximately 2.5 cm is associated with consistent use of stimulant medication over years, compared with negligible use of medication. The final height decrement appears to be associated with cumulative dose of stimulant medications [23]. However, final adult height in most children or youth is likely to remain minimally affected by stimulant treatment for ADHD [69][70].

Stimulant-treated children or youth with ADHD may experience a slight overall reduction in BMI [71], particularly if they are overweight when treatment begins [72]. This weight loss may help explain why stimulants sometimes delay pubertal growth-spurt timing slightly, compared with peers with ADHD who are not being treated with a stimulant [72].

Recommendation 8: Monitor growth parameters for all children and youth being treated with stimulants for ADHD.

NONSTIMULANT MEDICATIONS

Two long-acting nonstimulants, atomoxetine and guanfacine chlorohydrate XR, are approved by Health Canada for treating ADHD in children and youth 6 to 17 years old (Table 2) [73][75].

Clonidine, a short-acting nonstimulant, is a nonselective alpha adrenergic agonist. Although controlled trials using clonidine have shown slow but gradual improvement in ADHD symptoms and tics [76], paediatric use of clonidine is not approved by Health Canada at the present time.

Nonstimulants are considered to be second-line medications for managing ADHD symptoms, due to lower treatment response rates [77][81] and effect size [82] compared with stimulants. Although atomoxetine is often used in combination with stimulants for young persons experiencing only a partial response to a stimulant [77], one recent systematic review concluded that there is little evidence to support administering a stimulant and atomoxetine adjunctively [83].

Recommendation 9: Nonstimulant medications are second-line interventions for ADHD treatment. They are typically used when stimulants are contraindicated, ineffective or not tolerated.

Because nonstimulants lack both a mechanism of action linked to abuse potential (such as increased norepinephrine and dopamine release) and immediacy of effect (such as speed of action and feeling stimulated), their potential for abuse or diversion is low compared with stimulant medications [84]. Atomoxetine may also have a lower risk for weight loss and for exacerbating tics and has been reported to improve anxiety [85]. Studies supporting these benefits are limited, however.

Recommendation 10: For individuals with ADHD and a history of substance use disorders (SUDs), treatment with a nonstimulant or ER stimulant medication with lower risk for abuse and diversion should be considered as part of a multimodal intervention plan. More research is needed to provide evidence-based recommendations for atomoxetine’s effectiveness in alleviating anxiety in children and youth.

Guanfacine chlorohydrate XR has shown utility as a monotherapy [86] or when used adjunctively with a stimulant medication [73] for treating both ADHD and comorbid oppositional symptoms [87] in children and adolescents with ADHD.

Monitoring the AEs of nonstimulant medications

AEs associated with atomoxetine include gastrointestinal (GI) symptoms (e.g., appetite loss, upper abdominal pain), somnolence, headaches, moodiness, and irritability. Serious risks, such as suicide-related events [88] and hepatic disorders, are rare but should be screened for in all patients. Unless symptomatic, baseline liver function tests are not indicated. Norepinephrine reuptake inhibitors like atomoxetine can raise blood pressure and heart rate but increases do not differ from levels associated with MPH [89] or DEX [81].

Sedation, somnolence, and fatigue are common side effects with guanfacine XR. Orthostatic hypotension, bradycardia and syncopal episodes have also been reported [87][89]. Clonidine causes a higher frequency of side effects, like sedation, dizziness, and hypotension, compared with guanfacine. Raynaud’s phenomenon may occur with all nonstimulants [60]. Blood pressure monitoring to establish a baseline is recommended before starting treatment, during dose adjustments, at regular intervals during treatment and when treatment is stopped. Studies in children, youth, and adults have shown a dose-dependent prolongation of the QTc interval [90], although little is known about the clinical significance of this effect. One Federal Drug Administration report in the United States concluded that evidence is lacking to support the potential for drug interaction between stimulants and alpha-agonists [91][93], which implies that they can be used adjunctively with stimulants.

Recommendation 11: Monitor blood pressure in patients on alpha-adrenergic drugs (e.g., guanfacine XR and clonidine) before initiating treatment, following dose increases and periodically throughout treatment.

Atomoxetine is metabolized in the liver by the CYP2D6 (a cytochrome P450 enzyme) pathway to 4-hydroxyatomoxetine. The elimination half-life for atomoxetine can extend from 5 to 22 hours and its rate of clearance is 10% that of extensive metabolizers in persons who are slow CYP2D6 metabolizers. Longer half-life may be caused by genetic polymorphisms of the cytochrome P450 enzyme system or by drugs that inhibit this system (i.e., bupropion, paroxetine, fluoxetine) [94]. In such cases, an atomoxetine dose of 0.5 mg/kg/day (to a maximum 40 mg/day) is continued for 2 to 4 weeks before considering increasing the dose.

Unlike atomoxetine, alpha adrenergic drugs (e.g., guanfacine XR and clonidine) must be tapered slowly to prevent rebound hypertension, tachycardia or, more rarely, hypertensive encephalopathy.

Recommendation 12: Patients and their families must be counselled about the dangers of abruptly stopping guanfacine or clonidine.

In summary, children and youth with ADHD benefit from implementation of a multimodal treatment plan with specified goals developed through a shared understanding of the child or youth’s needs. For most families, clinical management includes accurate psychoeducation and inclusion of parent and school interventions, as well as management of general health and well-being, with ongoing conversations about sleep, diet and exercise. Medications are an important option for families to consider because they are safe and effective therapy for the symptoms of inattention, impulsivity and hyperactivity associated with ADHD. Psychostimulant medications are the firstline choice because they are generally safe and effective for use over months to years. When stimulants are not well tolerated or no longer effective, additional medication options, such as atomoxetine or guanfacine XR, are available.

Acknowledgements

This position statement has been reviewed by the Adolescent Health, Community Paediatrics and Drug Therapy and Hazardous Substances Committees of the Canadian Paediatric Society. It was also reviewed by representatives of the Canadian Academy of Child and Adolescent Psychiatry (CACAP).


CANADIAN PAEDIATRIC SOCIETY MENTAL HEALTH AND DEVELOPMENTAL DISABILITIES COMMITTEE

Members: Debbi Andrews MD (Chair), Susan Bobbitt MD, Alice Charach MD, Brenda Clark MD (past member), Mark E. Feldman MD (past Board Representative), Johanne Harvey MD (former Board Representative), Benjamin Klein MD, Oliva Ortiz-Alvarez MD, Sam Wong MD (Board Representative)

Liaisons: Sophia Hrycko MD, Canadian Academy of Child and Adolescent Psychiatry; Angie Ip MD, CPS Developmental Paediatrics Section; Aven Poynter MD, CPS Mental Health Section

Principal authors: Mark E. Feldman MD, Alice Charach MD, Stacey A. Bélanger MD, PhD


References

  1. American Academy of Pediatrics, Subcommittee on Attention-Deficit/Hyperactivity Disorder; Steering Committee on Quality Improvement and Management, Wolraich M, et al. ADHD: Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics 2011;128(5):1007–22.
  2. National Institute for Health and Care Excellence (NICE) Guidelines: Attention Deficit Hyperactivity Disorder: Diagnosis and Management (updated recommendations 2018). https://www.nice.org.uk/guidance/ng87 (Accessed May 23, 2018).
  3. Bolea-Alamañac B, Nutt DJ, Adamou M et al.; British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: Update on recommendations from the British association for psychopharmacology. J Psychopharmacol 2014;28(3):179–203.
  4. Charach A, Carson P, Fox S, Ali MU, Beckett J, Lim CG. Interventions for preschool children at high risk for ADHD: A comparative effectiveness review. Pediatrics 2013;131(5):e1584–604.
  5. Storebø OJ, Skoog M, Damm D, Thomsen PH, Simonsen E, Gluud C. Social skills training for attention deficit hyperactivity disorder (ADHD) in children aged 5 to 18 years. Cochrane Database Syst Rev 2011;(12):CD008223.
  6. Sonuga-Barke EJ, Brandeis D, Cortese S et al.; European ADHD Guidelines Group. Nonpharmacological interventions for ADHD: Systematic review and metaanalyses of randomized controlled trials of dietary and psychological treatments. Am J Psychiatry 2013;170(3):275–89.
  7. Rimestad ML, Lambek R, Zacher Christiansen H, Hougaard E. Short- and longterm effects of parent training for preschool children with or at risk of ADHD: A systematic review and meta-analysis. J Atten Disord. 2016;pii:1087054716648775 (Epub ahead of print).
  8. Kadesjö B, Gillberg C. The comorbidity of ADHD in the general population of Swedish school-age children. J Child Psychol Psychiatry 2001;42(4):487–92.
  9. Ferrin M, Moreno-Granados JM, Salcedo-Marin MD, Ruiz-Veguilla M, Perez-Ayala V, Taylor E. Evaluation of a psychoeducation programme for parents of children and adolescents with ADHD: Immediate and long-term effects using a blind randomized controlled trial. Eur Child Adolesc Psychiatry 2014;23(8):637–47.
  10. Bussing R, Zima BT, Mason DM, Meyer JM, White K, Garvan CW. ADHD knowledge, perceptions, and information sources: Perspectives from a community sample of adolescents and their parents. J Adolesc Health 2012;51(6):593–600.
  11. Fiks AG, Mayne S, Hughes CC, et al. Development of an instrument to measure parents’ preferences and goals for the treatment of attention deficit-hyperactivity disorder. Acad Pediatr 2012;12(5):445–55.
  12. Fiks AG, Mayne S, Debartolo E, Power TJ, Guevara JP. Parental preferences and goals regarding ADHD treatment. Pediatrics 2013;132(4):692–702.
  13. Renoux C, Shin JY, Dell’Aniello S, Fergusson E, Suissa S. Prescribing trends of attention-deficit hyperactivity disorder (ADHD) medications in UK primary care, 1995-2015. Br J Clin Pharmacol 2016;82(3):858–68.
  14. Wolraich ML, McKeown RE, Visser SN, et al. The prevalence of ADHD: Its diagnosis and treatment in four school districts across two states. J Atten Disord 2014;18(7):563–75.
  15. Brault MC, Lacourse É. Prevalence of prescribed attention-deficit hyperactivity disorder medications and diagnosis among Canadian preschoolers and school-age children: 1994-2007. Can J Psychiatry 2012;57(2):93–101.
  16. Charach A, Dashti B, Carson B, et al. Attention deficit hyperactivity disorder: Effectiveness of treatment in at-risk preschoolers; long-term effectiveness in all ages; and variability in prevalence, diagnosis, and treatment [Internet], AHRQ Comparative Effectiveness Reviews 2011; Report No.:12-EHC003-EF.
  17. Storebø OJ, Krogh HB, Ramstad E, et al. Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. BMJ 2015;351:h5203.
  18. Banaschewski T, Soutullo C, Lecendreux M, et al. Health-related quality of life and functional outcomes from a randomized, controlled study of lisdexamfetamine dimesylate in children and adolescents with attention deficit hyperactivity disorder. CNS Drugs 2013;27(10):829–40.
  19. Danckaerts M, Sonuga-Barke EJ, Banaschewski T, et al. The quality of life of children with attention deficit/hyperactivity disorder: A systematic review. Eur Child Adolesc Psychiatry 2010;19(2):83–105.
  20. van der Kolk A, Bouwmans CA, Schawo SJ, Buitelaar JK, van Agthoven M, Hakkaartvan Roijen L. Association between quality of life and treatment response in children with attention deficit hyperactivity disorder and their parents. J Ment Health Policy Econ 2014;17(3):119–29.
  21. DeVito EE, Blackwell AD, Kent L, et al. The effects of methylphenidate on decision making in attention-deficit/hyperactivity disorder. Biol Psychiatry 2008;64(7):636–9.
  22. Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV. Do stimulants protect against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics 2009;124(1):71–8.
  23. Swanson JM, Arnold LE, Molina BSG, et al.; MTA Cooperative Group. Young adult outcomes in the follow-up of the multimodal treatment study of attention-deficit/hyperactivity disorder: Symptom persistence, source discrepancy, and height suppression. J Child Psychol Psychiatry 2017;58(6):663–78.
  24. Lufi D, Gai E. The effect of methylphenidate and placebo on eye-hand coordination functioning and handwriting of children with attention deficit hyperactivity disorder. Neurocase 2007;13(5):334–41.
  25. Prasad V, Brogan E, Mulvaney C, Grainge M, Stanton W, Sayal K. How effective are drug treatments for children with ADHD at improving on-task behaviour and academic achievement in the school classroom? A systematic review and meta-analysis. Eur Child Adolesc Psychiatry 2013;22(4):203–16.
  26. Cox DJ, Merkel RL, Moore M, Thorndike F, Muller C, Kovatchev B. Relative benefits of stimulant therapy with OROS methylphenidate versus mixed amphetamine salts extended release in improving the driving performance of adolescent drivers with attention-deficit/hyperactivity disorder. Pediatrics 2006;118(3):e704–10.
  27. Zoëga H, Rothman KJ, Huybrechts KF, et al. A population-based study of stimulant drug treatment of ADHD and academic progress in children. Pediatrics 2012;130(1):e53–62.
  28. Dalsgaard S, Leckman JF, Mortensen PB, Nielsen HS, Simonsen M. Effect of drugs on the risk of injuries in children with attention deficit hyperactivity disorder: A prospective cohort study. Lancet Psychiatry 2015;2(8):702–9.
  29. Man KK, Chan EW, Coghill D, et al. Methylphenidate and the risk of trauma. Pediatrics 2015;135(1):40–8.
  30. Dalsgaard S, Østergaard SD, Leckman JF, Mortensen PB, Pedersen MG. Mortality in children, adolescents, and adults with attention deficit hyperactivity disorder: A nationwide cohort study. Lancet 2015;385(9983):2190–6.
  31. Hechtman L, Swanson JM, Sibley MH, et al.; MTA Cooperative Group. Functional adult outcomes 16 years after childhood diagnosis of attention-deficit/hyperactivity disorder: MTA results. J Am Acad Child Adolesc Psychiatry 2016;55(11):945–52. e2.
  32. Klein RG, Mannuzza S, Olazagasti MA, et al. Clinical and functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 2012;69(12):1295–303.
  33. Canadian Paediatric Society. Children with School Problems, 2012. Preschool/Kindergarten Questionnaire. [Online]. http://www.cps.ca/uploads/issues/preschool-kindergarten-questionnaire-CWSP.pdf (Accessed September 12, 2018).
  34. Canadian Paediatric Society. Children with School Problems, 2012. School Questionnaire (6–18 yrs). [Online]. http://www.cps.ca/uploads/issues/schoolquestionnaire-6-18years-CWSP.pdf (Accessed September 12, 2018).
  35. Canadian ADHD Resource Alliance. SNAP-IV 26 - Teacher and Parent Rating Scale. [Online]. http://www.caddra.ca/pdfs/caddraGuidelines2011SNAP.pdf (Accessed January 30, 2018).
  36. Murray DW, Kollins SH, Hardy KK, et al. Parent versus teacher ratings of attention-deficit/hyperactivity disorder symptoms in the preschoolers with attention-deficit/hyperactivity disorder treatment study (PATS). J Child Adolesc Psychopharmacol 2007;17(5):605–20.
  37. Sanchez RJ, Crismon ML, Barner JC, Bettinger T, Wilson JP. Assessment of adherence measures with different stimulants among children and adolescents. Pharmacotherapy 2005;25(7):909–17.
  38. Marcus SC, Wan GJ, Kemner JE, Olfson M. Continuity of methylphenidate treatment for attention-deficit/hyperactivity disorder. Arch Pediatr Adolesc Med 2005;159(6):572–8.
  39. Lage M, Hwang P. Effect of methylphenidate formulation for attention deficit hyperactivity disorder on patterns and outcomes of treatment. J Child Adolesc Psychopharmacol 2004;14(4):575–81.
  40. Steele M, Weiss M, Swanson J, Wang J, Prinzo RS, Binder CE. A randomized, controlled effectiveness trial of OROS-methylphenidate compared to usual care with immediate-release methylphenidate in attention deficit-hyperactivity disorder. Can J Clin Pharmacol 2006;13(1):e50–62.
  41. Gau SS, Chen SJ, Chou WJ, et al. National survey of adherence, efficacy, and side effects of methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan. J Clin Psychiatry 2008;69(1):131–40.
  42. Christensen L, Sasané R, Hodgkins P, Harley C, Tetali S. Pharmacological treatment patterns among patients with attention-deficit/hyperactivity disorder: Retrospective claims-based analysis of a managed care population. Curr Med Res Opin 2010;26(4):977–89.
  43. Charach A, Fernandez R. Enhancing ADHD medication adherence: Challenges and opportunities. Curr Psychiatry Rep 2013;15(7):371.
  44. Kidwell KM, Van Dyk TR, Lundahl A, Nelson TD. Stimulant medications and sleep for youth with ADHD: A meta-analysis. Pediatrics 2015;136(6):1144–53.
  45. Thiruchelvam D, Charach A, Schachar RJ. Moderators and mediators of long-term adherence to stimulant treatment in children with ADHD. J Am Acad Child Adolesc Psychiatry 2001;40(8):922–8.
  46. Feldman M, Bélanger S. Extended-release medications for children and adolescents with attention-deficit hyperactivity disorder. Paediatr Child Health 2009;14(9):593–602.
  47. Swanson J, Gupta S, Lam A, et al. Development of a new once-a-day formulation of methylphenidate for the treatment of attention-deficit/hyperactivity disorder: Proof-of-concept and proof-of-product studies. Arch Gen Psychiatry 2003;60(2):204–11.
  48. Teuscher NS, Adjei A, Findling RL, Greenhill LL, Kupper RJ, Wigal S. Population pharmacokinetics of methylphenidate hydrochloride extended-release multiple-layer beads in pediatric subjects with attention deficit hyperactivity disorder. Drug Des Devel Ther 2015;9:2767–75.
  49. Parasampuria DA, Schoedel KA, Schuller R, et al. Do formulation differences alter abuse liability of methylphenidate? A placebo-controlled, randomized, double-blind, crossover-study in recreational drug users. J Clin Psychopharmacol 2007;7(5):450–67.
  50. Dupont RL, Coleman JJ, Bucher RH, Wilford BB. Characteristics and motives of college students who engage in nonmedical use of methylphenidate. Am J Addict 2008;17(3):167–71.
  51. Wilens TE, Adler LA, Adams J, et al. Misuse and diversion of stimulants prescribed for ADHD: A systematic review of the literature. J Am Acad Child Adolesc Psychiatry 2008;47(1):21–31.
  52. Ahmed R, McCaffery KJ, Aslani P. Factors influencing parental decision making about stimulant treatment for attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2013;23(3):163–78.
  53. Faraone SV, Biederman J, Zimmerman B. An analysis of patient adherence to treatment during a 1-year, open-label study of OROS methylphenidate in children with ADHD. J Atten Disord 2007;11(2):157–66.
  54. Charach A, Fernandez R. Enhancing ADHD medication adherence: Challenges and opportunities. Curr Psychiatry Rep 2013;15(7):371.
  55. Greenhill L, Kollins S, Abikoff H, et al. Efficacy and safety of immediate-release methylphenidate treatment for preschoolers with ADHD. J Am Acad Child Adolesc Psychiatry 2006;45(11):1284–93.
  56. Cohen SC, Mulqueen JM, Ferracioli-Oda E, et al. Meta-analysis: Risk of tics associated with psychostimulant use in randomized, placebo-controlled trials. J Am Acad Child Adolesc Psychiatry 2015;54(9):728–36.
  57. Erenberg G. The relationship between Tourette syndrome, attention deficit hyperactivity disorder, and stimulant medication: A critical review. Semin Pediatr Neurol 2005;12(4):217–21.
  58. Law SF, Schachar RJ. Do typical clinical doses of methylphenidate cause tics in children treated for attention-deficit hyperactivity disorder? J Am Acad Child Adolesc Psychiatry 1999;38(8):944–51.
  59. Gadow KD, Sverd J, Sprafkin J, Nolan EE, Ezor SN. Efficacy of methylphenidate for attention-deficit hyperactivity disorder in children with tic disorder. Arch Gen Psychiatry 1995;52(6):444–55.
  60. Coulombe J, Powell J, Hatami A, McCuaig C, Renet S, Marcoux D. Diseases of abnormal sensitivity to cold in children on psychostimulant drugs. J Cutan Med Surg 2015;19(2):121–4.
  61. Syed RH, Moore TL. Methylphenidate and dextroamphetamine-induced peripheral vasculopathy. J Clin Rheumatol 2008;14(1):30–3.
  62. Singletary F, Sharma N, Jerath R. Psychostimulant-induced vasculopathy: A retrospective study in a pediatric rheumatology clinic [abstract]. Arthritis Rheumatol 2015;67(suppl 10).
  63. Man KK, Coghill D, Chan EW, et al. Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system. Transl Psychiatry 2016;6(11):e956.
  64. Eiland LS, Bell EA, Erramouspe J. Priapism associated with the use of stimulant medications and atomoxetine for attention-deficit/hyperactivity disorder in children. Ann Pharmacother 2014;48(10):1350–5.
  65. Burnett AL. Anxiety disorders in patients with idiopathic priapism: Risk factor and pathophysiologic link? J Sex Med 2009;6(6):1712–8.
  66. Hailpern SM, Egan BM, Lewis KD, et al. Blood pressure, heart rate, and CNS stimulant medication use in children with and without ADHD: Analysis of NHANES data. Front Pediatr 2014;2:100.
  67. Cooper WO, Habel LA, Sox CM, et al. ADHD drugs and serious cardiovascular events in children and young adults. N Engl J Med 2011;365(20):1896–904.
  68. Bélanger SA, Warren AE, Hamilton RM, et al. Cardiac risk assessment before the use of stimulant medications in children and youth. Paediatr Child Health 2009;14(9):579–92.
  69. Harstad EB, Weaver AL, Katusic SK, et al. ADHD, stimulant treatment, and growth: A longitudinal study. Pediatrics 2014;134(4):e935–44.
  70. Biederman J, Spencer TJ, Monuteaux MC, Faraone SV. A naturalistic 10-year prospective study of height and weight in children with attention-deficit hyperactivity disorder grown up: Sex and treatment effects. J Pediatr 2010;157(4):635–40, 640.e1.
  71. Faraone SV, Spencer TJ, Kollins SH, Glatt SJ. Effects of lisdexamfetamine dimesylate treatment for ADHD on growth. J Am Acad Child Adolesc Psychiatry 2010;49(1):24–32.
  72. Zachor DA, Roberts AW, Hodgens JB, Isaacs JS, Merrick J. Effects of long-term psychostimulant medication on growth of children with ADHD. Res Dev Disabil 2006;27(2):162–74.
  73. Wilens TE, Bukstein O, Brams M, et al. A controlled trial of extended-release guanfacine and psychostimulants for attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry 2012;51(1):74–85.e2.
  74. Biederman J, Melmed RD, Patel A, McBurnett K, Donahue J, Lyne A. Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD. CNS Spectr 2008;13(12):1047–55.
  75. Gorman DA, Gardner DM, Murphy AL, et al. Canadian guidelines on pharmacotherapy for disruptive and aggressive behaviour in children and adolescents with attention-deficit hyperactivity disorder, oppositional defiant disorder, or conduct disorder. Can J Psychiatry 2015;60(2):62–76.
  76. Palumbo DR, Sallee FR, Pelham WE Jr, Bukstein OG, Daviss WB, McDermott MP. Clonidine for attention-deficit/hyperactivity disorder: I. Efficacy and tolerability outcomes. J Am Acad Child Adolesc Psychiatry 2008;47(2):180–8.
  77. Kratochvil CJ, Milton DR, Vaughan BS, Greenhill LL. Acute atomoxetine treatment of younger and older children with ADHD: A meta-analysis of tolerability and efficacy. Child Adolesc Psychiatry Ment Health 2008;2(1):25.
  78. Schwartz S, Correll CU. Efficacy and safety of atomoxetine in children and adolescents with attention-deficit/hyperactivity disorder: Results from a comprehensive meta-analysis and metaregression. J Am Acad Child Adolesc Psychiatry 2014;53(2):174–87.
  79. Dittmann RW, Cardo E, Nagy P, et al. Efficacy and safety of lisdexamfetamine dimesylate and atomoxetine in the treatment of attention-deficit/hyperactivity disorder: A head-to-head, randomized, double-blind, phase IIIb study. CNS Drugs 2013;27(12):1081–92.
  80. Newcorn JH, Kratochvil CJ, Allen AJ, et al.; Atomoxetine/Methylphenidate Comparative Study Group. Atomoxetine and osmotically released methylphenidate for the treatment of attention deficit hyperactivity disorder: Acute comparison and differential response. Am J Psychiatry 2008;165(6):721–30.
  81. Wigal SB, McGough JJ, McCracken JT, et al. A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder. J Atten Disord 2005;9(1):275–89.
  82. Cheng JY, Chen RY, Ko JS, Ng EM. Efficacy and safety of atomoxetine for attention-deficit/hyperactivity disorder in children and adolescents-meta-analysis and meta-regression analysis. Psychopharmacology (Berl) 2007;194(2):197–209.
  83. Treuer T, Gau SS, Méndez L, et al. A systematic review of combination therapy with stimulants and atomoxetine for attention-deficit/hyperactivity disorder, including patient characteristics, treatment strategies, effectiveness, and tolerability. J Child Adolesc Psychopharmacol 2013;23(3):179–93.
  84. Clemow DB, Walker DJ. The potential for misuse and abuse of medications in ADHD: A review. Postgrad Med 2014;126(5):64–81.
  85. Kratochvil CJ, Newcorn JH, Arnold LE, et al. Atomoxetine alone or combined with fluoxetine for treating ADHD with comorbid depressive or anxiety symptoms. J Am Acad Child Adolesc Psychiatry 2005;44(9):915–24.
  86. Sallee FR, McGough J, Wigal T, Donahue J, Lyne A, Biederman J; SPD503 STUDY GROUP. Guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder: A placebo-controlled trial. J Am Acad Child Adolesc Psychiatry 2009;48(2):155–65.
  87. Findling RL, McBurnett K, White C, Youcha S. Guanfacine extended release adjunctive to a psychostimulant in the treatment of comorbid oppositional symptoms in children and adolescents with attention-deficit/hyperactivity disorder. J Child Adolesc Psychopharmacol 2014;24(5):245–52.
  88. Mosholder AD, Gelperin K, Hammad TA, Phelan K, Johann-Liang R. Hallucinations and other psychotic symptoms associated with the use of attentiondeficit/hyperactivity disorder drugs in children. Pediatrics 2009;123(2):611–6.
  89. Biederman J, Melmed RD, Patel A, et al.; SPD503 STUDY GROUP. A randomized, double-blind, placebo-controlled study of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Pediatrics 2008;121(1):e73–84.
  90. Knebel W, Ermer J, Purkayastha J, Martin P, Gastonguay MR. Population pharmacokinetic/pharmacodynamic modeling of guanfacine effects on QTc and heart rate in pediatric patients. AAPS J 2014;16(6):1237–46.
  91. Hirota T, Schwartz S, Correll CU. Alpha-2 agonists for attention-deficit/hyperactivity disorder in youth: A systematic review and meta-analysis of monotherapy and add-on trials to stimulant therapy. J Am Acad Child Adolesc Psychiatry 2014;53(2):153–73.
  92. Fenichel RR. Combining methylphenidate and clonidine: The role of postmarketing surveillance. J Child Adolesc Psychopharmacol 2009;5(3):155–6.
  93. Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF. Meta-analysis: Treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry 2009;48(9):884–93.
  94. Sauer JM, Ponsler GD, Mattiuz EL, et al. Disposition and metabolic fate of atomoxetine hydrochloride: The role of CYP2D6 in human disposition and metabolism. Drug Metab Dispos 2003;31(1):98–107.
  95. Daley D, van der Oord S, Ferrin M, et al.; European ADHD Guidelines Group. Behavioral interventions in attention-deficit/hyperactivity disorder: A metaanalysis of randomized controlled trials across multiple outcome domains. J Am Acad Child Adolesc Psychiatry 2014;53(8):835–47, 847.e1–5.
  96. Pelham WE Jr, Fabiano GA, Waxmonsky JG, et al. Treatment sequencing for childhood ADHD: A multiple-randomization study of adaptive medication and behavioral interventions. J Clin Child Adolesc Psychol 2016;45(4):396–415.
  97. Evans SW, Owens JS, Wymbs BT, Ray AR. Evidence-based psychosocial treatments for children and adolescents with attention deficit/hyperactivity disorder. J Clin Child Adolesc Psychol 2018;47(2):157–98.
  98. Fabiano GA, Vujnovic RK, Pelham WE, et al. Enhancing the effectiveness of special education programming for children with attention deficit hyperactivity disorder using a daily report card. School Psychol Rev 2010;39(2):219–39.
  99. Evans SW, Owens JS, Bunford N. Evidence-based psychosocial treatments for children and adolescents with attention-deficit/hyperactivity disorder. J Clin Child Adolesc Psychol 2014;43(4):527–51.
  100. Abikoff H, Gallagher R, Wells KC, et al. Remediating organizational functioning in children with ADHD: Immediate and long-term effects from a randomized controlled trial. J Consult Clin Psychol 2013;81(1):113–28.
  101. Cortese S, Ferrin M, Brandeis D, et al.; European ADHD Guidelines Group (EAGG). Cognitive training for attention-deficit/hyperactivity disorder: Metaanalysis of clinical and neuropsychological outcomes from randomized controlled trials. J Am Acad Child Adolesc Psychiatry 2015;54(3):164–74.
  102. Sonuga-Barke E, Brandeis D, Holtmann M, Cortese S. Computer-based cognitive training for ADHD: A review of current evidence. Child Adolesc Psychiatr Clin N Am 2014;23(4):807–24.
  103. Micoulaud-Franchi JA, Geoffroy PA, Fond G, Lopez R, Bioulac S, Philip P. EEG neurofeedback treatments in children with ADHD: An updated meta-analysis of randomized controlled trials. Front Hum Neurosci 2014;8:906.
  104. Holtmann M, Sonuga-Barke E, Cortese S, Brandeis D. Neurofeedback for ADHD: A review of current evidence. Child Adolesc Psychiatr Clin N Am 2014;23(4):789–806.
  105. Stevenson J, Buitelaar J, Cortese S, et al. Research review: The role of diet in the treatment of attention-deficit/hyperactivity disorder–an appraisal of the evidence on efficacy and recommendations on the design of future studies. J Child Psychol Psychiatry 2014;55(5):416–27.
  106. Hurt EA, Arnold LE. An integrated dietary/nutritional approach to ADHD. Child Adolesc Psychiatr Clin N Am 2014;23(4):955–64.
  107. Cerrillo-Urbina AJ, García-Hermoso A, Sánchez-López M, Pardo-Guijarro MJ, Santos Gómez JL, Martínez-Vizcaíno V. The effects of physical exercise in children with attention deficit hyperactivity disorder: A systematic review and meta-analysis of randomized control trials. Child Care Health Dev 2015;41(6):779–88.
  108. Kamp CF, Sperlich B, Holmberg HC. Exercise reduces the symptoms of attention-deficit/hyperactivity disorder and improves social behaviour, motor skills, strength and neuropsychological parameters. Acta Paediatr 2014;103(7):709–14.
  109. Barkley RA, ed. Stimulant and nonstimulant medications for childhood ADHD. In: Attention Deficit Hyperactivity Disorder: A Handbook for Diagnosis and Treatment, 4th edn. New York, NY: The Guildford Press, 2014.

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated: Oct 26 2018