ADHD in children and youth: Part 3—Assessment and treatment with comorbid ASD, ID, or prematurity
Posted: Oct 24 2018
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Brenda Clark, Stacey A. Bélanger; Canadian Paediatric Society, Mental Health and Developmental Disabilities Committee
Paediatr Child Health 2018, 23(7):485–490.
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 3, which focuses on associated autism spectrum disorder, intellectual disability, and prematurity, include the challenges of diagnostic assessment, common presentations, the role of genetics, and treatment, including the benefits of physical activity. Recommendations are based on current guidelines, evidence from the literature, and expert consensus.
Keywords: Autism; ADHD; Intellectual disability; Prematurity
Neurodevelopmental deficits associated with autism spectrum disorder (ASD), intellectual disability (ID), or premature birth mimic and overlap with ADHD symptoms that affect learning, behaviour, and daily functioning. However, ADHD symptoms may also overshadow or mask symptoms of all three conditions, leading to delayed diagnosis. Expertise in evaluating ASD, ID, and the sequelae of prematurity as well as associated comorbidities, and a multidisciplinary approach that includes environmental, behavioural, and learning interventions, are required for patients with these conditions. This position statement highlights symptom presentation and trajectories of impairment in these three distinct yet convergent conditions, to enhance understanding and help guide treatment planning. The roles of genetics and therapies (both pharmacological and nonpharmacological) are examined.
ASD AND ADHD
Unlike the DSM-IV-TR, the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), refers to ASD and ADHD (now ASD+ADHD) not as mutually exclusive diagnoses but as conditions that may, and often do, coexist in the same individual . ASD treatment centres on social communication and interaction skill deficits, repetitive and stereotyped behaviour, and restricted interests as core features . However, more recent and increasing evidence of comorbidity with childhood-onset neurodevelopmental disorders like ADHD, with specific impacts on function and prognosis for children and youth with ASD, has broadened scope of treatment –. Comorbidity between ASD+ADHD is high. More than 50% of individuals with ASD meet criteria for ADHD, and up to 50% of children with ADHD have ASD traits –.
Although ADHD+ASD each have distinct core symptoms, children with ASD can present with inattention, impulsivity, and hyperactivity, while children with ADHD often show ASD-like social deficits –. Both conditions have early onset, present more commonly in males, and have high heritability and comorbidity with other psychiatric, developmental, and neurological disorders . It is common for young children with ASD+ADHD to receive their ADHD diagnosis first. In these children, there is a higher probability for a significant delay (3 years on average) in the diagnosis of ASD, compared to individuals diagnosed with ASD+ADHD concurrently or with ASD alone .
Children with ASD+ADHD present with more impairment in cognitive functioning, more severe behaviour problems and greater psychopathology than individuals with either disorder alone –. Impairments include more severe and pronounced autistic symptoms, greater difficulties with social and communication skills, self-care, adaptive and executive functioning skills, as well as problematic internalizing behaviours (such as anxiety and depression). Maladaptive disruptive behaviours (e.g., tantrums, aggression, emotional dysregulation) and stereotypic or repetitive behaviours are more common in children with ASD+ADHD –. Comorbid psychiatric disorders (e.g., schizophrenia, bipolar, depression, anxiety, disruptive behaviours, and sleep and tic disorders) are also more prevalent. ASD+ADHD is associated with significant learning difficulties and specific language impairment, especially in children and youth with higher functioning ASD ––.
ASD+ADHD share genetic factors . Rare copy number variants (<1% population frequency), chromosomal deletions and duplications with a greater effect size are common in children with ADHD and show significant overlap with genetic abnormalities found in ASD and ID –. Genetic syndromes with clinical features of ASD+ADHD include fragile X syndrome, tuberous sclerosis, 22q11 deletion, and Williams syndrome –.
Loci underlying ASD+ADHD have been identified on chromosomes 12, 16, and 18 –. Sixteen single-nucleotide polymorphisms associated with ASD have been identified from ADHD studies, while 25 single-nucleotide polymorphisms appear to be related to ADHD based on ASD studies . These studies further suggest shared heritability of ASD+ADHD . Research into the role of genetics in ASD is evolving rapidly, with genetic associations and causes being frequently reported. Remaining up-to-date with the literature in this area is important for treatment planning.
When medication is indicated, recent guidelines and meta-analyses concur that psychostimulants should be considered as the first-line treatment for children diagnosed with ASD+ADHD . ADHD should be treated in individuals with ASD using the same treatment algorithm as for ADHD alone. However, children and youth with ASD+ADHD are more likely to be nonresponders and to have side effects –.
Irritability with emotional outbursts is the most common adverse effect of stimulants in children with ASD+ADHD –. Increased stereotypic behaviours, agitation, dysphoria, and psychotic symptoms have also been reported –. Limited studies have suggested that atomoxetine treatment improves ADHD symptoms in individuals with ASD+ADHD. However, the length of time required for full medication response is longer than for stimulants .
A significant reduction of ADHD symptoms was observed in children with ASD+ADHD who were treated with guanfacine and guanfacine extended-release . Antipsychotic medications are not indicated for treatment of core symptoms of ADHD . Although stimulant medications are used most often to treat children with ASD+ADHD , combined pharmacology in cases complicated by comorbidities is also common, with adjunctive use of an antidepressant, antipsychotics or a mood stabilizer . Because these children tend to be complex, regular multidisciplinary assessment is often needed to guide behavioural and learning goals.
Physical activity is known to alleviate ADHD symptoms  and improve social skills in children and youth with ASD , and should be integrated into daily routines. While evidence supports a broad range of behavioural interventions for children diagnosed with either ASD or ADHD, few studies to date have demonstrated efficacy for the nonpharmacological or behavioural management of individuals with ASD+ADHD . Children with ASD benefit from early intense behavioural interventions, but ADHD symptoms must not be overlooked. Before initiating pharmacological management, standard evidence-based interventions for ADHD should be implemented, including behavioural parent and teacher training, with a strong school-based component, including individualized education plans (IEPs) and academic supports . Referral to a tertiary level care centre is often required to access clinicians with expertise in a broad range of developmental and mental health disorders.
INTELLECTUAL DISABILITY AND ADHD
The diagnosis of intellectual disability (ID), also to be known as intellectual developmental disorder in the WHO’s most current International Classification of Diseases (ICD-11), was also revised in the DSM-5 to replace the DSM-IV diagnosis of mental retardation. ID is a chronic condition diagnosed in 2% to 3% of children >5 years of age that often co-occurs with—and affects prognosis for—other neurodevelopmental and mental health disorders. ID is characterized by developmental deficits in cognitive function (i.e., reasoning, problem-solving, planning, abstract thinking, judgment, academic learning, and learning from experience) or in adaptive functioning, such that individuals may be unable to meet developmental and sociocultural standards for personal independence and social responsibility . In ID, intelligence quotient (IQ) scores are ≥2 standard deviations below the population mean . Based on DSM-5 criteria, adaptive function rather than an IQ score is used to define the level of severity (mild, moderate, severe, profound ID), because support requirements depend largely on the level of adaptive function .
ADHD is the most common neurodevelopmental disorder comorbid with ID. Prevalence rates are three to four times higher in children or youth with ID than in the general population . However, diagnosing ADHD in individuals with ID is particularly difficult because lower intellectual functioning can affect attention and behaviour , leading to diagnostic ‘overshadowing’ . ADHD-like symptoms may also mask (or reveal) a coexisting organic or psychiatric illness .
Symptoms of inattention, hyperactivity and impulsivity may be present when academic requirements exceed a child’s intellectual level. In such cases, symptoms typically abate in nonacademic settings. As per the DSM-5, a diagnosis of ADHD in ID can only be made when the core symptoms of ADHD are excessive for developmental age and occur in two or more settings. No standardized behaviour questionnaires exist at the present time to measure ADHD symptoms in special populations. Although psychological tests cannot be used to diagnose ADHD, intelligence screening for children or youth with ADHD symptoms who are also experiencing significant difficulties with key academic skills (reading, spelling, math) is justified to rule out ID as a contributing factor . Furthermore, a multidisciplinary approach and specific expertise in assessing behaviour disorders in children and youth with ID are required to fully determine whether inattention, hyperactivity, and impulsivity are due to comorbid ADHD rather than to ID alone .
Research on comorbid ID+ADHD is still sparse, but some features are clear: core symptoms of ADHD tend to be more severe  and less likely to remit with age  in individuals with comorbid ID. Moreover, higher rates of agitation, aggressive and self-injurious behaviours , autistic traits or stereotypic behaviours (e.g., rocking) and conduct problems  are common. Adaptive functioning, especially in areas of daily living and social communication, is generally impaired in children or youth with comorbid ID+ADHD .
At least 50% of ID cases are associated with chromosomal (e.g., fragile X, Klinefelter or Turner syndrome), metabolic (e.g., aminoacidemias, phenylketonuria, galactosemia) or neurological conditions (e.g., neurofibromatosis, tuberous sclerosis, myotonic dystrophy) –. Rare copy number variants found in children with ADHD have also been associated with ID (see the Genetics section under ASD/ADHD, above). Clinicians need to investigate patients with ID+ADHD in accordance with the companion statement published in this issue.
Optimizing environmental and academic interventions, such that a child’s or youth’s cognitive and emotional needs are addressed concurrently, is an important aspect of treatment. Coordinated therapies help to lower the medication dose required and minimize risk for adverse effects. Evidence for the beneficial effects of physical exercise in individuals with ADHD  suggests that exercise programs should be encouraged for children and youth with ID+ADHD.
The clinical effectiveness of short-acting methylphenidate for managing ADHD symptoms in children with comorbid ID+ADHD has been studied in randomized controlled trials . A response rate to methylphenidate of 45% to 66% for the combined condition significantly exceeds that of placebo, but is below the response rate for ADHD alone . An IQ above 50 predicts a better response to stimulants , while very low (severe, profound) IQ levels predict poorer response . Moreover, children with ID+ADHD who receive short-acting methylphenidate are at higher risk for such side effects as tics and social withdrawal .
Recent Canadian guidelines recommend that when medication is needed to manage ADHD symptoms in children or youth with ID, psychostimulants should be used first . When response to psychostimulants combined with psychotherapy is suboptimal, the use of nonstimulants is recommended. For functionally disabling behaviours not responsive to behavioural interventions and/or to stimulants and nonstimulants, neuroleptics (e.g., Risperidone) may be used, with extreme caution due to their significant burden of side effects . Close monitoring for adverse metabolic and neurological events, as outlined in the Canadian Alliance for Monitoring Effectiveness and Safety of Antipsychotics (CAMESA) guidelines, is mandatory . Data is sparse for the use of nonstimulants and long-acting psychostimulants in children and youth with ID+ADHD. The need for more evidence to support prescribing and monitoring of drugs in this population remains profound .
PREMATURITY AND ADHD
Since the 1990s, advances in neonatal intensive care have increased survival rates for preterm births significantly . Research studies and follow-up programs now define very low birth weight and extremely low birth (ELBW) weight as <1,500 g and <1,000 g, respectively. ‘Very preterm’ (VPT) and ‘extremely preterm’ (EPT) refer to infants born before 30 weeks and 26 weeks gestation, respectively . Premature infants are surviving with lower rates of disability, including cerebral palsy, severe visual or hearing impairments, and severe cognitive impairment defined by developmental quotient or IQ .
However, while major disability rates have decreased, the occurrence of sequelae associated with low birth weight and prematurity, such as milder cognitive impairment and associated neurodevelopmental and mental health difficulties during childhood, is increasing –. Almost 50% of children born EPT or ELBW have developmental disorders . Cognitive impairment, inattention, hyperactivity, internalizing behaviour disorders, and social interaction difficulties persist well beyond the preschool period, affecting educational achievement in later childhood –.
In a cohort of ELBW children who were followed to 6 years plus 4 months of age, an increased prevalence of disability was noted by school age, compared with same-aged peers . Cognitive impairment was the most common disability (IQ 1–2 SD below the mean identified in 25% of children and IQ >2 SD below mean in 21%). The frequency of cognitive impairment rose to 41% when ELBW children were compared with contemporary classmates.
One study followed 219 ELBW children until they reached 8 years of age. The authors identified significantly more chronic conditions than in normal birth weight (NBW) controls, along with increasing need for supports and services beyond routine requirements .
There is also an association between gestational age (GA) or birth weight and cognitive scores by school age . As GA increases >26 weeks, impairments decrease almost linearly until 32 weeks GA. Even past this point, and correcting for prematurity, the mean remains 5 SD lower than for NBW peers –. Although most school-related learning difficulties, supportive services, IEPs, and special education placements are determined by lower cognitive scores, more recent research has highlighted attentional or behavioural concerns and their impact on learning –.
Behaviour outcomes in premature infants
Common difficult-to-manage behaviours relate to symptoms associated with ADHD: inattention, internalizing disorders (anxiety, depression, withdrawal, somatic complaints), and social difficulties . This cluster of difficulties is collectively referred to as the ‘preterm behavioural phenotype’ . Disruptive behaviour disorders, such as oppositional defiant disorder, conduct disorder, and hyperactive/impulsive presentation in ADHD, are seen less frequently –.
In a 2001/2003 birth cohort of ELBW and EPT children assessed at kindergarten, approximately twice as many met criteria for ADHD combined presentation compared with NBW controls, but nearly five times as many met criteria for ADHD inattentive presentation .
At 8 years of age, ELBW children showed significantly more behavioural problems than NBW children, with higher rates of ADHD and anxiety disorder . Almost twice as many had ADHD inattentive presentation compared with NBW controls . At 14 years of age , the same cohort showed significantly higher rates of subnormal IQ (14% <70) and need for IEPs (45%). Previously reported symptoms of ADHD inattentive presentation, anxiety and social problems persisted through school age. These symptoms were not accompanied by comorbid oppositional defiant disorder, conduct disorder or disruptive behaviours characteristic of ADHD . This finding is supported by other studies –, which showed that EPT children are more likely to have a psychiatric disorder at 11 years compared with NBW controls .
A Swedish national cohort study of more than a million children followed and treated for ADHD from age 6 to 19 years  showed a stepwise increase in odds ratios for ADHD medication with increasing prematurity at birth, compared with term infants. This effect was not explained by genetic, perinatal or socioeconomic status, although the last factor modified risk for ADHD in moderately preterm births .
This research has been supported by another study , which compared cohorts of later preterm (34 to 37 weeks GA) and term (37 to 42 weeks GA) children. They found no statistically significant difference in the cumulative incidence of ADHD between groups, which suggests that late preterm and term infants have similar rates of ADHD.
Most provinces and territories in Canada have follow-up programs to monitor developmental outcomes in this population, for at least 2 years postbirth and sometimes longer. However, only a few jurisdictions continue surveillance to school age, when symptoms are most likely to affect function. Monitoring development and behaviour in children born prematurely, identifying concerns early, and ensuring timely interventions, supports and services can improve outcomes significantly. As yet, there is no specific literature on treating ADHD symptoms in ELBW/EPT children or those born prematurely. When medications are needed, the same protocols are followed as for children born at term, but special consideration must be given to the screening, monitoring and treatment of internalizing behaviour disorders.
- Children and youth with ASD, ID, and born prematurely are at increased risk for ADHD and experience greater impairment due to symptoms. Clinicians must be aware of high comorbidity and assess for ADHD symptoms in children and youth with these conditions. Follow-up programs should monitor developmental, cognitive, and emotional outcomes at least until school entry and, preferably, until children are integrated and adapting well to their school environment and their academic performance is stable.
- The diagnostic evaluation of ADHD in children and youth with concurrent neurodevelopmental conditions requires a multidisciplinary approach and an expert assessment of associated behaviour disorders.
- When medication is indicated for treating ADHD symptoms in individuals with ASD and ID, psychostimulants should be used first and as part of a comprehensive treatment program.
- There is a positive role for regular physical activity in mitigating ADHD symptoms, and every effort should be made to promote these activities and integrate them into daily routines.
- Side effects of ADHD medication are more common in children and youth with ASD and ID.
- Further research is needed to develop an evidence base for using behaviour modification, long-acting psychostimulants, and nonstimulants to treat children and youth with ASD, ID or those born premature.
This position statement has been reviewed by the Adolescent Health, Community Paediatrics and Fetus and Newborn 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: Brenda Clark MD, Stacey A. Bélanger MD, PhD
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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.