The focus of treatment for children with ASD, as depicted in the case composite, is to improve social relationships and function, with safety taken into consideration. Best practices involve a collaborative child-and family-centered approach. To consent to treatment, the child and family need to understand the diagnoses, the purpose, risks and benefits of the proposed treatments, the risks and benefits of alternative treatments, and the risks and benefits of declining treatment (Riddle, 2019; Walter et al., 2020). Therapeutic interventions for the social deficits of ASD include social skills training and behavioral therapy. Sensory-related challenges can improve with occupational and physical therapy. Speech therapy is frequently recommended for speech and communication deficiencies. Repetitive actions, avoidance, social anxiety, and perseveration associated with ASD can often be helped with concurrent cognitive-behavioral therapy (CBT). Pharmacological interventions may be considered when a child with ASD is showing emotional or behavioral dysregulation, including aggression, irritability, and impulsive behaviors that could cause harm to self or others. Such behaviors as hyperactivity and anxiety-related avoidance can similarly lead to impaired relationships and are often the impetus for bringing the child into care.
Although there are no U.S. Food and Drug Administration (FDA)–approved medications for treatment of the core symptoms of ASD, there are medications that are approved for the treatment of irritability and aggressive behaviors and co-occurring mental disorders.
Irritability and Aggressive Behaviors. The only FDA-approved medications for ASD–related irritability and aggression are risperidone and aripiprazole for children aged 5 (risperidone) and 6 (aripiprazole) to 17. Risperidone is a second-generation antipsychotic (SGA) that blocks dopamine at the D2 receptor and serotonin 5HT2A receptors. The dosage range for children is 0.25 mg (for children weighing <20 kg [<44 lbs]) or 0.5 (for children weighing ≥20 kg [≥44 lbs]); with a maximum dosage of 3 mg per day (Riddle, 2019). In the experience of the first author (L.B.), a low dose at bedtime can lead to rapid and sustained improvement in behaviors with low side effects.
Aripiprazole is often referred to as a third-generation antipsychotic (TGA) because the mechanism of action is different from SGAs; it has partial agonist activity at dopamine D2 receptors and serotonin 5HT1A receptors and blocks activity at the serotonin 5HT2A receptors. The recommended dosage range is 2 mg to 10 mg daily. The first author tends to start at 1 mg to 2 mg at bedtime and titrate up slowly by approximately 2 mg weekly, generally seeing a good response by 5 mg to 7.5 mg nightly.
Common adverse effects of risperidone and aripiprazole include sedation and anticholinergic effects (e.g., dry mouth, constipation). Major risks include weight gain, metabolic abnormalities (i.e., elevated glucose, cholesterol, or triglyceride levels), and persistent involuntary movements (e.g., tardive dyskinesia). All of these risks are worse for risperidone than aripiprazole (Mano-Sousa et al., 2020; Riddle, 2019; Scahill et al., 2016). The risk of metabolic abnormalities is linked to weight gain. Although weight gain is initially less with aripiprazole compared to risperidone, the differences with long-term treatment may not persist (DeVane et al., 2019).
Before starting the medication, a personal and family history should be obtained of metabolic or cardiovascular disease, weight/body mass index, waist circumference, blood pressure, fasting plasma glucose, and fasting lipid profile. Weight should be monitored at all follow-up visits. For children, there are no specific guidelines for monitoring; however, the standard of practice is to use the guidelines of the American Diabetes Association et al. (2014), which include monitoring blood pressure, fasting plasma glucose, and lipid profile at 12 weeks and annually (Riddle, 2019). The first author recommends obtaining a comprehensive metabolic panel at baseline because it includes liver function.
For children who are insured by Medicaid, many states require the clinician to submit an Authorization for Antipsychotic Prescription prior to treatment, at 3 months, and then every 6 months (Part E, Substance Abuse and Mental Health Services Administration, 2019). The clinician is required to document the target symptoms and laboratory results, as well as the score on the Abnormal Involuntary Movement Scale. Gynecomastia and amenorrhea are potential adverse effects associated with risperidone due to elevations in prolactin. A prolactin level should be obtained if symptomatic, and if hyper-prolactinemia is present, a decrease in dosage should be considered.
Attention, Impulsivity, and Hyperactivity. There are three ADHD presentations in the DSM-5: predominantly inattentive, predominantly hyperactive/impulsive, and combined. Children with ASD and ADHD share impairments of social skills deficits, distractibility and executive functioning (Antshel & Russo, 2019; Walter et al., 2020), and soft neurological motor symptoms (Reiersen et al., 2008). Differentiating the two disorders is difficult when inattention is the predominant presentation of ADHD. The motor and behavioral symptoms more clearly differentiate ASD and ADHD. Whereas children with ASD may display stereotypic and repetitive behaviors, children with ASD who also display general hyperactivity and impulsivity are more likely to have co-occurring ADHD (APA, 2013; Shephard et al., 2019). In children with ADHD–inattentive type, the differential is more challenging.
For children, stimulant medications (methylphenidate or amphetamine compounds) are the first line treatments for ADHD (Wolraich et al., 2019). Methylphenidate has been found to be effective in improving attention and reducing impulsivity and hyperactivity and is well-tolerated for treatment of comorbid ADHD among children and adolescents with ASD (Ventura et al., 2020). The first author's clinical approach is to start with a long-acting methylphenidate, particularly if the child is struggling with aggression, which can be intensified when treated with amphetamine-based stimulants. Parents/guardians and teachers can help by noting changes in behavior once the treatment begins.
The starting dose of long-acting methylphenidate (Concerta®) is 18 mg each morning and has a duration of effect of up to 12 hours. Parents/guardians are asked to start the medication on a day when the child will be home with them to assess for effectiveness and side effects. A checklist of routine daily activities (e.g., chores, homework completion) can often help parents/guardians identify how well the child is able to attend and control impulsive/hyperactive behaviors, and it is valuable information for the clinician to understand where impairments lie to better target symptoms. Caution must be used, as some children with ASD can experience an increase in anxiety when treated with stimulants. An increase in stereotyped/repetitive behaviors (which can resemble tics), obsessive-compulsive disorder (OCD)–like behaviors, and irritability are also possible risks after initiation of a stimulant. Parents/guardians are asked to discontinue the stimulant and call the clinician if the child experiences worrisome side effects. As the half-life of stimulants is fairly short, side effects typically resolve quickly, and long-term side effects are rare.
Non-stimulant medications, such as guanfacine/clonidine (alpha agonists) and atomoxetine (norepinephrine reuptake inhibitor) are FDA–approved for ADHD in children aged ≥6 years and are frequently useful for adjunctive therapy with stimulants (using the lowest effective dose of stimulant). In clinical studies, non-stimulants are most useful for treating agitation/hyperactivity related to ADHD and are somewhat less effective for inattention and rarely used as monotherapy for ADHD. Overall, children with ASD respond better to guanfacine or atomoxetine than clonidine (Reiersen & Todd, 2008). Side effects include sedation and hypotension, so these medications are given at bedtime.
Anxiety and Compulsive Behaviors. The prevalence of anxiety disorders or symptoms among young children with ASD is higher than in children with other neurodevelopmental disorders (Vasa et al., 2020). Diagnosable anxiety disorders co-occur with ASD, as do atypical expressions of anxiety that concern ASD–related challenges. Kerns et al. (2014) reported that 63% of a sample of 59 youths with ASD presented with anxiety that impaired functioning, with 17% having only diagnosable cooccurring anxiety disorders (i.e., specific phobias, generalized anxiety disorder [GAD], and social phobias were most common), 15% having only atypical ASD–related anxiety symptoms (e.g., worries and fears around routine, novelty, unusual specific fears, atypical social fears without fears of rejection, compulsive behaviors with ambiguous purpose), and 31% having a diagnosable anxiety disorder with co-occurring ASD–related anxiety symptoms.
In general, nonpharmacological evidence-based treatments, such as CBT, should be recommended prior to a medication trial. Children and their parents/guardians benefit from cognitive and behavioral anxiety management strategies. The newly drafted guidelines published by the Academy of Child and Adolescent Psychiatry (Walter et al., 2020) recommend, for children and adolescents ages 6 to 18 with diagnosed social anxiety, GAD, separation anxiety, specific phobia, or panic disorder, that CBT be offered as the first-line treatment for mild to moderate severity. For children with greater anxiety severity and related impairment, they recommend combination treatment (CBT and selective serotonin reuptake inhibitor [SSRI]) be offered preferentially over CBT alone or a SSRI monotherapy alone due to evidence that the combination is a more effective short-term treatment for anxiety in children and adolescents than either treatment alone (Walter et al., 2020). Vasa et al. (2020) also recommend an ASD–specific therapy called Pivotal Response Treatment (PRT) that focuses on providing and rewarding appropriate social communication and is also helpful in reducing anxiety (Lei et al., 2017).
The only FDA–approved medication for treatment of an anxiety disorder (e.g., GAD) in children and adolescents is the serotonin-norepinephrine reuptake inhibitor (SNRI), duloxetine, yet it is considered a secondary treatment due to having more adverse effects than SSRIs (Riddle, 2019; Walter et al., 2020). SSRIs that have FDA approval for the treatment of major depressive disorder or OCD in children and adolescents and have been shown to have efficacy for the treatment of anxiety disorders include fluoxetine, escitalopram, sertraline, and fluvoxamine (Riddle, 2019).
Before starting a child on a SSRI, it is important to review the potential for adverse effects with the parents/guardians and child. Although the risk is low, all antidepressants carry a FDA boxed warning for suicidal thinking and behavior up through age 24, so close monitoring is recommended during the first few months of treatment and following dosage increases (Walter et al., 2020). Behavioral activation/agitation that includes increased motor or mental restlessness, insomnia, impulsiveness, talkativeness, disinhibited behavior, and aggression can occur with SSRI treatment, so starting the dose low and increasing the dose gradually to the lowest effective dose over several months is recommended. Best practice guidelines for the discontinuing treatment of children with anxiety disorders who are taking anti-depressants recommend a slow taper during a relatively stress-free period, following at least 12 months of symptom remission (Walter et al., 2020). In the experience of the first author, sertraline or escitalopram may be good choices due to having a short metabolic half-life and the ability to discontinue or taper the medication more rapidly in case of adverse side effects. Of all SSRIs/SNRIs, escitalopram has the lowest risk for pharmacokinetic drug–drug interactions (Riddle, 2019).
Sleep Dysregulation. Children with sleep dysregulation are at risk for anxiety, behavioral problems, daytime sleepiness, and poorer health and general functioning. There are currently no FDA–approved medications for sleep disorders among children. For treating insomnia and disrupted sleep behaviors in children and adolescents with ASD, the American Academy of Neurology (AAN; Williams Buckley et al., 2020) recommend behavioral strategies as a first-line approach. Parents/guardians can be asked to monitor sleep behaviors (Shapiro, 1998). If the sleep problem does not improve with behavioral strategies (e.g., CBT-Insomnia), they recommend the use of low-dose melatonin. Melatonin has been found to be safe for children for short-term use, but the safety for long-term use remains unknown. The AAN guidelines provide evidence that melatonin alone or with CBT-Insomnia can reduce bedtime resistance, sleep-onset latency, sleep continuity, and total sleep time in children with ASD (Williams Buckley et al., 2020). The first author finds that starting with the lowest dose (1 mg) of the standard formulation and titrating to a maximum of 5 mg nightly is well tolerated. If the child's sleep difficulties have not improved within 1 month, further evaluation is warranted.