Growing evidence of pharmacotherapy effectiveness in managing attention-deficit/hyperactivity disorder in young children with or without autism spectrum disorder: a minireview
Hamza A. Alsayouf*Hamza A. Alsayouf*
Dr. Hamza Alsayouf Clinic, Amman, Jordan
Many children with autism spectrum disorder (ASD) also have attention-deficit/hyperactivity disorder (ADHD). ADHD in children is associated with increased risk of negative outcomes, and early intervention is critical. Current guidelines recommend psychosocial interventions such as behavioral training as the first line of therapy in managing ADHD symptoms in children with or without ASD. Where symptoms are refractory to these interventions, medications such as stimulants, α2-adrenergic agonist inhibitors, selective norepinephrine reuptake inhibitors, and second-generation antipsychotics are recommended. However, these pharmacotherapies do not have regulatory approval for use in children of preschool age, and evidence on their safety and efficacy in this population has historically been very limited. Since publication of the current guidelines in 2020, several new randomized controlled trials and real-world studies have been published that have investigated the efficacy and tolerability of these medications in preschool children with ADHD, with or without comorbid ASD. Here, we provide a review of the key findings of these studies, which suggest that there is growing evidence to support the use of pharmacological interventions in the management of ADHD in preschool children with comorbid ASD.
1 Introduction
Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurodevelopmental condition in childhood (1) and occurs in 40-70% of children with autism spectrum disorder (ASD) (2). There is a marked overlap in symptoms between ADHD and ASD (3) that is suggestive of a related etiology (4-6), with similar alterations observed in e.g., neural connectivity, sensory processing, sleep patterns, and motor and impulse control.
Updates to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria now allow the diagnosis of ADHD in children with a comorbid diagnosis of ASD (7, 8). It is hoped that this will allow more children to be fully diagnosed and treated effectively (1, 8, 9). Standard ADHD rating scales have not yet been validated for patients with comorbid ASD, and careful differential diagnosis of ADHD is required based on observation of the child in a variety of settings (9).
ADHD is characterized by hyperactivity, inattention, and impulsivity (7), which can have lasting negative effects that extend into adulthood (10, 11). Preschool children with ADHD tend to have difficulties in developing fine motor abilities and foundational skills (e.g., writing, basic mathematics, and prereading), and they struggle to socialize due to aggression, disruptiveness, and impulsivity (10, 12). Symptoms of ADHD can exacerbate and perpetuate impairments in children with comorbid ASD, further increasing the risk of negative outcomes in these children and placing an even greater burden on families and caregivers (9).
Several medications have been evaluated in clinical trials for efficacy in the management of ADHD symptoms. Many of these may also have a beneficial effect in patients with comorbid ASD and mainly include stimulants, selective norepinephrine reuptake inhibitors, α-2 adrenergic agonists, and second-generation antipsychotics (13). However, the only pharmacological therapies that the United States’ Food and Drug Administration (FDA) have approved are risperidone (approved 2006) and aripiprazole (approved 2009) for the treatment of children with ASD from the ages of 5 and 6 years, respectively, and these medications are indicated for the comorbid symptoms of irritability and aggression that are frequently associated with this condition (14, 15).
Currently, the most recent guidelines from the American Academy of Pediatrics (AAP) from 2020 recommend that psychosocial interventions (e.g., parent training and behavioral classroom interventions) be used as first-line therapy in children with ASD to manage their core symptoms and any comorbid challenging behaviors, with pharmacotherapies to be used as an adjunct where such interventions are not sufficiently effective (1, 9). However, due to the many potential barriers in place related to access to non-pharmacological treatment strategies (16), combined with the increasing number of children diagnosed with ASD (17), most clinicians do not follow these guidelines (16), and many preschool children either receive medications off-label or remain untreated (18). Nevertheless, there is consensus that early diagnosis and treatment are associated with better social, mental health, educational, and functional outcomes in children with ADHD and ASD (19-21).