Autism Spectrum Disorder Nursing CE Course for APRNs

nosis can reliably begin as young as 14 months. According to their findings, once a toddler is identified as having ASD, there is a low chance that they will test within expected developmental levels at 3 years. In a 2020 systematic review, Tanner and Dounavi (2020) reinforced these conclusions, demonstrating that several ASD signs and symptoms emerge during the first year of life and can be detected between 6 and 18 months.

Additionally, ASD poses a sizeable economic burden, particularly due to the widespread lack of accommodations for people who have ASD. Patients who have ASD incur higher health care costs compared to the general population. Most of these costs are found to be from therapy services, medications, and outpatient visits, not inpatient services, showing that ASD is typically managed in the community setting. Individuals who have ASD also have higher rates of other physical and mental health conditions, adding to health care costs (Matin et al., 2022). According to a 2017 report by Autism Speaks—a foundation dedicated to advancing research, advocacy, and support for ASD—the cost of caring for persons who have ASD reached $268 billion in 2015. This number is predicted to rise to $461 billion by 2025 if more efficacious interventions and support services are not implemented across the lifespan. Most costs in the US are related to adult services, reaching up to $196 billion each year. On average, it costs $60,000 a year to care for someone who has autism, and most of these expenses are related to special education and lost caregiver income. In addition, the medical expenditures for children and adolescents who have ASD are about 4.1 to 6.2 times greater than for those who do not have ASD (Autism Speaks, 2017). For each individual with ASD, the cost of education, health care, and other services combined ranged from $1.4 to $2.4 million (Hyman et al., 2020).

Etiology and Contributing Factors

              While the exact cause remains under investigation, most researchers believe a combination of genetics and environmental factors contributes to the development of ASD. Several genes are linked to higher support needs in communication, social cognition, and behavior that patients who have ASD typically experience. However, specific genetic causes of ASD are only identified in 10% to 20% of cases. Patients who have similar genetic variants can be diagnosed along diverse areas of the spectrum (Rylaarsdam & Guemez-Gamboa, 2019). More than 1,000 genes reported to be associated with ASD are thought to be involved in functions at the neuronal junction (synapse) or the transmission site between nerve cells (neurons) or to affect the number of neurons produced. Other genes that are associated with ASD may control the activity of proteins and genes. These changes occur in the temporal and frontal lobes, which impact language, emotions, and social behavior, all characteristic changes associated with ASD (National Library of Medicine, 2021).

Much of what is known about the heritability of ASD is based on sibling prevalence, monozygotic twins, sex distribution, and risk pertaining to relatedness (Augustyn, 2024). Data from a study funded by the National Institutes of Health highlighted the wide variability in symptom degree among twins despite sharing the same DNA (Castelbaum et al., 2020). Castelbaum and colleagues (2020) explored data on 366 identical twin pairs with and without ASD. If one twin had ASD, there was a 96% chance the other twin was also affected. However, their symptoms varied greatly. One cohort study in Sweden found that heritability differs among males and females. In males, heritability was estimated at 87%, and in females, heritability was estimated at 75.7%. This study shows that the prevalence and underlying causes of autism may differ among the sexes (Sandin et al., 2024). Multiple published studies previously demonstrated an increased incidence of ASD among children born to parents of advanced age. The risk of ASD had been found to be as high as 40% to 50% for older parents, with a 10% to 20% reduced risk for younger parents. Lyall and colleagues (2020) further investigated parental age association with ASD-related outcomes in individuals with a high familial risk for ASD. They did not observe significant associations between ASD and advanced parental age. They found that of the 397 high familial-risk children in the study, there was an increased risk of ASD diagnosis with younger paternal age, increased cognitive functioning with increased paternal age, and decreased cognitive score with both parents of younger parental age (Lyall et al., 2020).

In a large population-based cohort study in Sweden, Xie and colleagues (2019) found that a history of parental mental illness is associated with an increased likelihood of ASD in a child. Xie and colleagues (2019) evaluated more than 500,000 participants and found that 63.1% of patients who have ASD had a parent with a history of mental and/or neurological disorders, compared with 45.4% of those who do not have ASD. In addition, a family history of multiple conditions was associated with a higher odds ratio of ASD, including a history of ASD, intellectual disability, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), schizophrenia, depression, bipolar disorder, personality disorder, cerebral palsy, and epilepsy. Furthermore, the more closely related the affected family member was, the higher the likelihood of ASD became (Xie et al., 2019). This increased risk of ASD associated with parental mental health conditions may be attributed to genetic factors, environmental exposures, timing of exposures, and the interactions between each of these. Research from Kaplan (2024) showed that the likelihood of ASD increased if both parents had a psychiatric diagnosis and an increased likelihood of ASD as the number of psychiatric illnesses increased. These researchers suggest further research on the impacts of maternal stress associated with ASD. The research also suggests family-based interventions that could provide a stronger foundation for children's social and emotional development among this population (Kaplan, 2024).

              Evidence suggests that environmental factors can determine up to 40% to 50% of ASD likelihood (Masini et al., 2020). The most discussed environmental factor correlated with ASD has been immunization. This erroneous connection, spawned from a since-retracted report published in 1998, ignited a frenzy over the perceived safety concerns of childhood immunizations, specifically the measles, mumps, and rubella (MMR) vaccine. Immunization coverage for MMR was above 90% prior to this article and subsequently dropped to below 80%. Concurrently, annual cases of measles went from below 100 to over 2,000 (DeStefano & Shimabukuro, 2019). Despite an overwhelming amount of evidence since then that there is no link between vaccines and ASD diagnosis, caregivers remain hesitant to immunize related to this association. Another likely contributing factor is the timing of typical ASD diagnosis after receiving many childhood immunization series. The Vaccine Adverse Event Reporting System, the Vaccine Safety Datalink, and the CDC's established Clinical Immunization Safety Assessment Project are ways to report, track, and connect healthcare providers with vaccine safety information. Continued evidence, not only disputing this association but also on the etiology of ASD, has the potential to improve vaccine hesitancy. Earlier screening and diagnosis may also assist in disproving this myth (Gabis et al., 2022).

According to a systematic review by Zhong and colleagues (2020), higher or moderate intake of prenatal/multivitamins, folic acid, and vitamin D reduced the likelihood of ASD. However, the results have not been consistent enough for the authors to conclude a causal relationship. Other environmental factors that have been investigated for a possible association with ASD etiology are exposure to drugs, exposure to toxic substances, parental age, nutrition, and fetal environment. There have been significant associations found between ASD risk and injury or trauma at birth, multiple births, low birth weight, neonatal anemia, hyperbilirubinemia, and umbilical cord complications. Additionally, fetal exposure to sex steroids (e.g., testosterone and estrogen) is a potential risk factor for ASD. Potential maternal nutrient deficiencies such as vitamin D and short intervals between pregnancies may increase risk. Further relationships have been established between ASD prevalence and maternal weight (obesity and underweight). Additional environmental factors that have been associated in research with ASD include maternal exposure to substances (e.g., alcohol, smoke, medications), maternal use of valproic acid (Valproate) and selective serotonin uptake inhibitors (SSRIs), maternal diseases (e.g., diabetes mellitus, gestational diabetes), maternal viral and bacterial infections, and family history of autoimmune diseases (Masini et al., 2020).

Acknowledging that the causes of ASD are not well understood and continually evolving, the National Institute of Environmental Health Sciences (NIEHS, 2024) has listed the following factors as having the most decisive evidence involving the events before and during birth. The following factors are unlikely to cause ASD by themselves but appear to facilitate spectrum characteristics when combined with genetic factors (NIEHS, 2024):

• advanced parental age at the time of conception
• prenatal exposure to air pollution or certain pesticides
• maternal obesity, diabetes, or other immune system disorders causing increased inflammation
• extreme prematurity or very low birth weight
• any labor and delivery complication leading to periods of oxygen deprivation (hypoxia) to an infant's brain

Key Features

The hallmark signs of ASD include ongoing social, communication, and interaction challenges and focused or repetitive behaviors and interests. ASD begins in early childhood, affects daily life, and is typically a lifelong condition, although specific symptoms may improve over time. In some children, the social and behavioral characteristics of ASD may manifest during the first year of life. For example, infants and young toddlers may focus intently on specific items, rarely make eye contact, or not meet certain developmental milestones. Other children develop neurotypically until age 2 or 3 and then withdraw, regress, or become indifferent to social interaction. The degree of support needed is primarily influenced by how communication, social functioning, and behaviors impact daily functioning, communication, interpersonal interactions, and development (Augustyn & von Hahn, 2022; CDC, 2024f; Koegel et al., 2019).

Verbal and nonverbal communication skills are commonly affected. Most children who have ASD will present with delayed onset of verbal communication, which is the most common reason caregiversseek consultation from a healthcare provider. Healthy developing children typically speak their first words between 10 and 18 months. On average, children who have ASD do not achieve this milestone until 36 months. While many children who have ASD can communicate verbally, at least one-third remain nonverbal throughout their lifespan, speaking few or no words (Koegel et al., 2019). People who have ASD can have difficulty using and understanding spoken language, gestures, eye contact, facial expressions, tone of voice, idioms, or other figures of speech. Affected persons often feel overwhelmed in social situations, have difficulty gauging personal space, and struggle to recognize and express emotions in themselves and understand the feelings of people around them (Augustyn & von Hahn, 2022; CDC, 2024f).

Repetitive behaviors and focused interests are core features of ASD and can manifest in various ways. These may include body movements, motions with external objects, staring at lights or spinning objects, rituals, and consistent routines (Augustyn & von Hahn, 2022; CDC, 2024f). According to the American Academy of Pediatrics (AAP), early signs of ASD include the following (Hyman et al., 2020):

• Age-specific:
  • does not respond to name by 12 months
  • does not point at objects to show interest by 14 months
  • does not engage in pretend play by 18 months
• General:
  • avoids eye contact
  • prefers to be alone (e.g., shows little or no interest in playing with peers)
  • has difficulty understanding other people's feelings or talking about their feelings
  • has delayed speech and language skills
  • exhibits echolalia (i.e., meaningless repetition of words or phrases)
  • gives unrelated answers to questions
  • has unexpected reactions to the way things sound, smell, taste, look, or feel
  • is significantly affected by minor changes (e.g., schedule/routine changes; being prevented from following particular rules)
  • has keen focus or interests (e.g., strong memory for specific topics)
  • makes repetitive movements like flapping hands, spinning in circles, or rocking back and forth

Table 2 summarizes the core features of ASD grouped into the three major categories of social, communication, and repetitive behaviors. In addition, most people who have ASD typically have diverse behaviors, habits, or needs beyond those listed above. Some of the most common include unexpected sleeping or eating habits; delayed cognitive, learning, or movement skills; gastrointestinal (GI) issues (e.g., constipation); unexpected fear perception (e.g., lack of fear or excessive fear); anxiety; or hyperactive and impulsive behaviors (CDC, 2024f).

Table 2

Core Features of Autism

Core Feature	Description
Social	minimal eye contact, gestures, or facial expression difficulty understanding the emotions and feelings of others difficulty playing with peers difficulty making and keeping friends less sharing of interests with others
Communication	lack of speech or slower speech acquisition unusual speech difficulty initiating or sustaining conversation less imitation and pretend play than expected for age
Repetitive Behaviors	repeated movements or activities (e.g., rocking, spinning, flapping) uncommon or highly focused interests (e.g., passionate about a certain topic or playing with the same toy) plays with parts of a toy instead of the whole toy (e.g., spinning the wheels of a toy car)

(CDC, 2024f; Hyman et al., 2020)

 

Screening and Diagnostic Process

The diagnosis of ASD is based on diagnostic tools and clinical judgment, as there are no laboratory tests or imaging studies to confirm the condition (Augustyn & von Hahn, 2022). The DSM-5-TR is the standard reference healthcare providers use to diagnose ASD as it outlines the primary diagnostic criteria (see Table 3). However, in clinical practice, an ASD diagnosis is rarely straightforward. Making a definitive diagnosis can be complex and time consuming. The process starts with screening modalities and typically involves a series of appointments and evaluations by an interprofessional health care team. No single tool should be used alone to diagnose an individual who has ASD (CDC, 2024b; Hyman et al., 2020; Weissman, 2024). The core features of the ASD screening and diagnostic process include the following:

• standardized observations of the child and routine surveillance
• screenings and assessments of their learning and cognitive abilities
• interviews to gather information about their behavior across multiple settings
• a comprehensive review of medical and developmental history (Hyman et al., 2020; Weissman, 2024)

The AAP recommends routine surveillance and developmental screenings at 9, 18, and 30 months. Along with routine developmental surveillance, the CDC and the AAP recommend that all children be screened specifically for ASD at 18 and 24 months and at any time concerns arise (CDC, 2024a). The priorities for these visits include asking caregiversabout concerns they have about their child's development or behavior, informal observation, and monitoring of symptoms in the context of routine health supervision. Developmental surveillance is insufficient to identify children who need further evaluation, as children who have ASD may not demonstrate all the characteristics in these brief office visits. Caregivers may not volunteer social and emotional concerns unless specifically asked. First-time caregiversmay not be aware that their child's behavior is unexpected or delayed. Therefore, standardized ASD-specific screening tools are indicated to help identify potential early manifestations and facilitate timely referrals (CDC, 2024a; Weissman, 2024).

According to Hyman and colleagues (2020), screening is a brief, standardized evaluation to identify anomalies and deviations from healthy developmental patterns. A screening tool helps detect concerns that may not be readily apparent otherwise. While screening does not confirm a diagnosis, it helps determine whether an additional evaluation is necessary. Healthcare providers are strongly encouraged to promptly refer all toddlers and children anytime an increased likelihood of ASD (or other developmental disorder) is suspected (Hyman et al., 2020; Weissman, 2024). Various ASD-specific screening tools are available, each targeting a specific age category and based on whether the child is being screened for the first time. First-tier (or level 1) tools are used to screen children for the first time to identify those with a significant chance of ASD from the general population (e.g., those at low risk), such as in primary care settings. Second-tier (or level 2) screening tools are used for children identified to be at risk based on developmental surveillance. Second-tier tools are usually more time consuming, help differentiate ASD from other developmental disorders, and often require more expertise to administer and interpret. Although ASD-specific screening tools are more accurate than general developmental tools for identifying ASD, they are criticized for their limited sensitivity (i.e., ability to identify young children who have ASD) and specificity (i.e., ability to differentiate ASD from other developmental conditions; Hyman et al., 2020; Weissman, 2024).

The Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) and the M-CHAT-R, with Follow-Up (M-CHAT-R/F) are the most frequently used tests in the US. The test carries a sensitivity of 85% and a specificity of 99% and has been validated as a first-tier screening tool for more than 16,000 children in primary care practices (Hyman et al., 2020; Weissman, 2024). The M-CHAT-R consists of 20 yes/no questions for caregivers, takes 5 to 10 minutes to complete, and can be used for children between 16 and 30 months old. The scoring and follow-up of the M-CHAT-R and M-CHAT-R/F are as follows (Hyman et al., 2020; Robins et al., 2024):

• A score of 0 to 2 indicates a low likelihood of ASD. Therefore, no additional intervention is required, and surveillance should continue at subsequent health supervision visits.
• A score of 3 to 7 denotes a medium likelihood of ASD, and the M-CHAT-R/F is recommended.
  • M-CHAT-R/F is a healthcare provider-conducted interview using the same 20 questions with additional follow-up inquiries.
• A score of 8 to 20 indicates a high likelihood of ASD and warrants an immediate referral to a specialist for a diagnostic evaluation and early intervention services.

In 2016, the US Preventive Services Task Force (USPSTF) announced that there was "insufficient" ("I" statement) evidence to support the universal role of primary care screening for ASD. An I-statement indicates that when the literature was synthesized regarding this recommendation, there was insufficient evidence to assess the balance of benefits versus harms in screening for ASD among patients whose caregiversor clinicians have raised no concerns about ASD. However, the USPSTF confirmed the availability of sufficient evidence to support current screening tools (including the M-CHAT-R) as reliable detectors of ASD when concerns arise. If either the caregiver or clinician is concerned about the child's development, the M-CHAT (or similar) screening tool should be administered. If negative, the child is unlikely to have ASD, and no further testing is recommended. If the M-CHAT is positive, then a follow-up interview with additional diagnostics should be pursued (Siu et al., 2016; USPSTF, 2016). The 2016 I-statement led to controversy among the research and medical communities regarding the risks, benefits, and potential harms of universal screening over the last few years, and the USPSTF recommendations have not changed since 2016. Still, the AAP, CDC, and other national organizations have not altered their strong recommendations for universal screening, as outlined above. An update regarding the USPSTF recommendations for ASD screening of young children is currently in process according to the USPSTF webpage (2021).

Table 3

Additional Screening Tools 

Tool	Ages	Description
Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist	6 to 24 months	first-tier screening tool 24-item caregiver-completed questionnaire
Rapid Interactive Screening Test for Autism in Toddlers	12 to 36 months	second-tier screening tool 9-item provider-completed interactive screening with clinician observation components
Caregiver's Observations of Society Interaction	16 to 35 months	additional community-context research is needed before being recommended as a first-tier screening tool 7-item caregiver-reported questionnaire
Screening Tool for Autism in 2-Year-Olds	24 to 36 months	not validated as a first-tier screening tool administered by a trained clinician interactive 20-minute play session that includes 12 activities evaluating play, attention, imitation, and communication
Autism Spectrum Screening Questionnaire	7 to 16 years	first-tier screening tool 27-item caregiver (or teacher) checklist

(CDC, 2024a; Hyman et al., 2020; Weissman, 2024)

If any screening tool identifies an area of concern, a formal, more thorough, and more structured evaluation of the child's development is recommended. Usually administered by a trained specialist, these more extensive assessments can include observations, structured tests, and additional questionnaires for caregivers(Hyman et al., 2020; Weissman, 2024).

Diagnostic Criteria

According to the CDC (2024b), the final diagnosis of ASD can be made by the primary care provider, or the patient can be referred to a neurodevelopmental pediatrician, developmental-behavioral pediatrician, geneticist, pediatric neurologist, pediatric psychologist, or early intervention programs for further assessment and diagnosis using the DSM-5-TR. According to the diagnostic criteria for ASD, a child must have persistent needs in all three areas of engaging with others (A1 to A3) plus at least two of the four types of restricted, repetitive behaviors (RRBs, B1 through B4) outlined in Table 4 (APA, 2022; CDC, 2024b).

Table 4

DSM-5-TR Diagnostic Criteria for ASD

A. Social communication and interaction Current or historical struggles engaging with others across several domains, as seen through all of the following (not exhaustive): building, sustaining, and comprehending relationships challenges with talking and interacting with people back and forth in a group setting body language, reading facial expressions

B. RRBs Actions, thoughts, and attention that are limited and remarkably consistent, sometimes referred to as RRBs. At least two of the following (previously or currently; examples are illustrative, not exhaustive): curiosity and attention to a limited number of topics patterns of speech and movement that are unchanging significantly increased or decreased response or attention to sights/sounds/smells/touches/feelings from their environment very consistent patterns in daily routines

The ability to perform successfully in crucial environments (home, school, work, friends) is significantly hindered by the condition.

Signs may increase with age and elevated communication and interaction requirements but are initially evident at a very young age.

Another condition, such as developmental delay or intellectual limitation, does not provide an enhanced reason for the symptoms.

(APA, 2022; CDC, 2024b; Interagency Autism Coordinating Committee [IACC], n.d.)

As highlighted in Table 4, the diagnostic criteria for ASD require clinicians to specify the current extent of symptoms in categories A and B. ASD is graded from 1 to 3 (see Table 5).

Table 5

Extent Levels of ASD

Level	Social Communication and Interaction	Focused, Repetitive Behaviors
Level 1 Requires support	without supports in place, needs in social communication have noticeable effects difficulty initiating social interactions may appear to have decreased interest in social interactions for those who are verbal, attempts to make friends are typically unexpected and unsuccessful	inflexibility of behavior significantly interferes with functioning in at least one context difficulty switching between activities problems with organization and planning interfere with personal independence
Level 2 Requires substantial support	marked deficits in verbal and nonverbal social communication social needs evident even with supports in place limited initiation of social interactions reduced or unexpected responses to social overtures from others	inflexibility of behavior, difficulty coping with change, and focused/repetitive behaviors occurring frequently enough to be obvious to a casual observer and require substantial support in various contexts difficulty adjusting focus or changing actions
Level 3 Requires very substantial support	severe needs in verbal and nonverbal communication skills that lead to severe effects very limited initiation of social interactions minimal response to social overtures from others	inflexibility of behavior, extreme difficulty coping with change, or other focused/repetitive behaviors that markedly interfere with functioning across all realms of life significant distress and difficulty changing focus or action

(APA, 2022; IACC, n.d.)

Common Accompanying Conditions

Several conditions often coexist with ASD, including developmental disorders, genetic disorders, medical illnesses, and mental health conditions. According to Hyman and colleagues (2020), this can prevent clinicians from recognizing the symptoms of ASD during early childhood, as it can be challenging to differentiate between ASD, intellectual developmental disorder, and social communication disorder. Approximately 30% of children who have ASD have an intellectual disability, and 30% have minimal verbal communication (Hyman et al., 2020).

Genetic Disorders

Children who have ASD should be evaluated for common coexisting genetic disorders such as fragile X syndrome, Rett's syndrome, and tuberous sclerosis complex (TSC), all linked to an increased likelihood of ASD (see Table 6). ASD is associated with a genetic cause in up to 25% of individuals (Augustyn, 2024). Genetic testing is more likely to find a genetic contribution to ASD if the child or another family member has ASD, if a family member has an ASD-related genetic change found through genetic testing, or if multiple family members have ASD. The most common genetic test for patients who have ASD is called a chromosomal microarray, which evaluates copy number variants (i.e., extra or missing components) associated with ASD. Chromosomal microarray testing demonstrates a genetic contribution in 5.4% to 14% of patients who have ASD and up to 17% to 42% of patients when copy number variants of uncertain significance were included. For patients who test negative for genetic findings on the chromosomal microarray analysis, whole-exome sequencing may be recommended as the next step in the diagnostic workup. Whole-exome sequencing evaluates genetic changes in portions of DNA and identifies a contribution in 8% to 20% of people who have ASD (Augustyn, 2024; Hyman et al., 2020).

Table 6

Common Coexisting Genetic Disorders

Genetic Disorder	Description
Fragile X syndrome	one of the most common causes of intellectual disability approximately 0.45% of individuals who have ASD have fragile X syndrome with the full mutation DNA testing for Fragile X syndrome is recommended for all patients who have ASD, especially males and those with a family history of male intellectual disability
Rett's syndrome	a neurodevelopmental disorder that primarily affects females characterized by expected early growth and development followed by a slowing of development, loss of purposeful use of the hands, unique hand movements, slowed brain growth, and intellectual disability can cause problems with walking and increase the risk of seizures approximately 60% of females who have Rett's syndrome have a phenomenology of ASD testing for Rett's syndrome is recommended for females who have ASD
TSC	a rare genetic disorder that causes benign tumors in the brain and other vital organs associated with a greater chance of developing epilepsy and ASD approximately 40% of all children who have TSC also have ASD strong association between seizures and ASD in children who have TSC, especially infant-onset seizures and infantile spasms

(Augustyn, 2024; Hyman et al., 2020; Mitchell et al., 2021; Specchio et al., 2020)

 

Seizures

Children who have ASD have an increased risk of seizures and epilepsy, even if another genetic condition is not identified. Children who have epilepsy are also at increased risk for ASD. Epilepsy risk among children who have ASD is 6.3%, and the rate of seizures among individuals who have ASD ranges from 7% to 23%, reaching 46% in some samples. Children whose language skills regress early in life appear to have a higher risk of developing epilepsy or seizure-like brain activity. Individuals diagnosed with both ASD and intellectual disability have the greatest risk of developing a seizure. Additional risk factors linked to an increased likelihood of seizures in individuals who have ASD include female sex and lower gestational age. Anomalies on electroencephalograms are common in children who have ASD, even without clinical seizure activity. Many symptoms of seizures overlap with ASD characteristics, making it challenging to differentiate between them. Symptoms also vary based on the type of seizure the child has and which part of the brain was affected; some demonstrate no visible signs at all (Hyman et al., 2020). According to Frye and colleagues (n.d.), some of the most common seizure symptoms include the following:

• loss of focus
• staring spells
• rapid eye movements/blinking rapidly
• involuntary body movements such as stiffening or muscle twitching
• loss of consciousness
• confusion or disorientation
• anxiousness or mood changes

GI Symptoms

While the etiology remains poorly understood, many children who have ASD experience coexisting GI symptoms, such as constipation, diarrhea, nausea, vomiting, gastrointestinal reflux disease, and abdominal pain. GI disorders are one of the most common comorbid medical conditions associated with ASD. However, they are often overlooked. Prevalence ranges from 9% to 91%, with the most comprehensive meta-analysis revealing that individuals who have ASD have a four-fold increase in risk of developing GI problems. Children who have ASD are also up to 5 times more likely to develop food refusal, food selectivity, and poor oral intake than children who do not have ASD. The most reported symptom is constipation. The ingestion of nonnutritive foods, known as pica, is also reported in individuals who have ASD, which is further associated with GI problems. Despite inconclusive evidence about the effectiveness of common restrictive diets such as the removal of gluten and/or casein, they are the most common dietary following in the ASD population. These may compound picky eating and contribute to nutritional deficits that the interdisciplinary team should note. Patients who have ASD often cannot verbally communicate their symptoms and have more nonspecific signs of GI symptoms, including irritability, self-injury, and aggression. This often corresponds to increased problem behaviors (Madra et al., 2021).

Depression and Anxiety

Depression and anxiety are common conditions associated with ASD. Depression among adolescents and adults who have ASD is one of the most common mental health conditions. In adults who have ASD, lifetime depression diagnosis is up to 40.2% (van Heijst et al., 2020). The co-occurrence of these conditions may result from the conditions having the same etiologic origin, sharing overlapping symptoms, or depression resulting from living with autism. The perceived amount of worry and lack of control are two overlapping symptoms between the conditions. Mastery, which is the extent to which someone feels they are in control of their lives, was found to be a relevant factor connecting depression and ASD (van Heijst et al., 2024). In children who have ASD, depression is the strongest predictor of suicidal thoughts or attempts. There was a 28% increase in children who have ASD whose caregivers reported "sometimes" or "very often" contemplation or attempting suicide than children who do not have ASD. Similar to GI symptoms, individuals who have ASD may not be able to express their depressive symptoms due to limited speech (McDougle, n.d.).

Anxiety disorder is one of the most common mental health comorbidities among children and adolescents who have ASD. Co-occurrence of these conditions negatively affects global functioning, and anxiety disorders should be considered a distinct construct from symptoms of ASD. There is also a higher rate of depressive symptoms in patients who have ASD and anxiety disorder. Individuals who have ASD and anxiety had a higher prevalence of symptoms of generalized anxiety disorder, separation anxiety, and specific phobias (Guerrera et al., 2022).

OCD

OCD is a mental health condition characterized by obsessive thoughts (e.g., intrusive, unwanted thoughts, urges, or images) that drive compulsive behaviors (e.g., handwashing, checking, doing tasks a certain number of times, arranging things) to decrease or get rid of the obsession. OCD is more prominent in children and teens who have ASD than in the general population, affecting 17% to 37% of children and adolescents who have ASD. Historically, OCD symptoms have been challenging for clinicians to distinguish from the repeated behaviors and focused interests typical of ASD (Martin et al., 2020). Individuals who have ASD may have features that overlap with OCD. However, children who have ASD typically are not aware of their obsessive thoughts or are distressed by them (Augustyn & von Hahn, 2022).

ADHD

Individuals who have ADHD, without co-occurrence of ASD, typically have an absence of deficiency in language skills, social behavior, or imaginary play (Augustyn & von Hahn, 2022). ADHD primarily presents with distraction, loss of belongings, and difficulty sustaining mental effort, compared to characteristics of ASD, such as children who seldom associate with others or struggle with communicating and interacting. Literature suggests that 50% to 70% of individuals who have ASD also have comorbid ADHD. The prevalence of selective attention related to ADHD is notably higher among individuals who have ASD. Overall, children with ASD-ADHD comorbidity have more severe ASD (Hours et al., 2022).

Sleep Disturbances

Sleep disturbances such as initiating and maintaining sleep are reported in 50% to 80% of children with ASD and may exacerbate problematic daytime behavior. Younger children often exhibit bedtime resistance, night-waking, and parasomnia, while adolescents often exhibit daytime sleepiness, shorter sleep duration, and delayed sleep onset. Coexisting conditions such as anxiety, epilepsy, and ADHD may exacerbate these sleep disturbances. Other contributors to these sleep disturbances should be explored, such as sleep apnea, gastroesophageal reflux, asthma, and seizures (Hyman et al., 2020).

Obesity

Childhood obesity is an ongoing public health issue associated with increased cardiovascular disease as well as numerous other physical and mental health conditions. Children who have developmental disabilities, which include ASD, are at a higher risk of excessive weight gain. The reasons behind this association are multifactorial, including selective eating, energy-dense food preferences, and medication side effects (e.g., second-generation antipsychotics [SGAs]; Sammels et al., 2022). Sammels and colleagues (2022) estimated a 17% prevalence of obesity among children who have ASD and a 58% increased risk of developing obesity in patients who have ASD.

Allergies

Skin and food sensitivities and allergies more commonly affect people who have ASD than those who do not have ASD. One study examined data on caregiver-reported food allergies in children who have ASD from the National Health Institute Survey. For study years 2011 to 2015, researchers found that food allergies were 2.5 times more common in children who have ASD (13.1%) than in children who do not have ASD (5.4%; Tan et al., 2019). Estrella and colleagues (2023) included 78 patients in a study looking at the association between food allergies and ASD using a skin prick test. More than 80% of patients who have ASD had positive skin prick tests compared to 42% of the control group. The most common food allergies were wheat, egg yolk, fish, egg whites, and chocolate (Estrella et al., 2023).

Risky Behaviors

Additional characteristics, risky behaviors, and challenges associated with ASD do not necessarily fit into the above categories. Some of the most common include the following:

• Children who have ASD are at an increased risk of self-injury and suicide.
• The risk of premature death is two- to 10-fold higher.
• Approximately 42% of individuals who have ASD engage in self-injurious behaviors, such as hand-hitting, self-cutting, or hair-pulling.
• Wandering and bolting are common, leading to an increased risk of getting lost or injured.
• Of children aged 4 to 10 years who have ASD, about half have tried to elope.
• Children who have ASD are 40 times as likely to die from drowning (Blanchard et al., 2021; CDC, 2024e; Hyman et al., 2020).

 

Treatment Options

              While there is no cure for ASD, various treatments can help minimize symptoms and maximize abilities. Primary treatment approaches include behavioral, developmental, educational, social-relational, pharmacological, psychological, and complementary/alternative. Therapies and behavioral interventions (i.e., nonpharmacological treatments) are designed to treat the support needs of ASD to build skills and minimize potential gaps in development. Because the manifestations of ASD can overlap with other disorders, treatment must focus on each individual's specific needs and not their diagnostic label. Therefore, treatment plans should be individualized, developmentally appropriate, and intensive, with a metric for periodically evaluating each patient's response to ensure interventions are adjusted accordingly. While most people who have ASD will benefit from treatment regardless of their age at diagnosis, it is generally accepted that the earlier these therapies are initiated, the better the outcomes (CDC, 2024g; National Institute of Child Health and Human Development [NICHD], 2021b).

As outlined by Hyman and colleagues (2020), the three primary goals of treatment for children who have ASD consist of the following:

• Support the child's core needs and associated co-occurring impairments (social communication, interaction, and restricted or repetitive behaviors and interests).
• Maximize functional independence by facilitating learning and adaptive skills.
• Eliminate, minimize, or prevent specific behaviors that may interfere with functional skills.

 

Nonpharmacological Therapies: Educational and Behavioral Interventions

In the US, educational law mandates the use of practices supported by evidence-based research. As outlined by the US Department of Education, the laws and guidelines regarding children who have ASD include the following:

• Individuals with Disabilities Education Improvement Act (IDEA)
• No Child Left Behind Act
• Every Student Succeeds Act (Hyman et al., 2020)

Therapy Options

Therapies that begin when the child is younger than 3 years old are referred to as early intervention services (EIS) and are typically organized through the state, local government, or school systems under part C of IDEA. IDEA guarantees free and appropriate education for every child who has a disability (including ASD). Each state or territory develops individual policies for implementing IDEA (Hyman et al., 2020; US Department of Education, n.d.). EIS has effectively improved behavior, functional skills, and communication in children who have ASD. The goal of EIS is to support each child's needs over time to enhance functioning. In a small percentage of patients, areas of concern may be minimized to the extent that they no longer cause disability. While treatment strategies vary based on each child's age, functioning, and individual needs, EIS typically includes the following core therapy groups: speech and language therapy (SLP), physical therapy, occupational therapy (OT), and social skills training (SST; see Table 7). These core groups are traditionally integrated as vital components of ASD behavioral and communication therapies (Steinbrenner et al., 2020).

Table 7

Core Therapy Groups

Therapy	Description
OT	OT helps children address cognitive, physical, social, motor, play, and academic/learning skills. OT teaches strategies to help each child live as independently as possible, focusing on self-care skills (e.g., eating, dressing, bathing). It can also help manage sensory triggers and build relational skills.
SLP	SLP helps with skills in verbal, nonverbal, and social communication. SLP seeks to help each child communicate in more useful and functional ways and may include interventions such as strengthening exercises of the mouth, jaw, or neck; matching emotions with appropriate facial expressions; using picture boards; and modulating tone of voice. SLP may incorporate technology (e.g., tablets or speech-output devices) and sign language as adjunctive communication avenues.
Physical therapy	Physical therapy targets any motor development delays by improving coordination and posture. It helps children develop and advance gross motor, fine motor, and fundamental movement by promoting exercise and structured play. Physical therapy can help decrease maladaptive behaviors and aggression and guide children to play games, sports, and engage physically with their peers.
SST	SST denotes a range of interventions designed to build the capabilities required to interact with others, such as conversation and problem-solving skills. SST is often incorporated into ASD support programs and may include training across several areas (e.g., eye contact, greeting, initiating conversation, body language, empathy).

(CDC, 2024g; Steinbrenner et al., 2020)

Services can be provided by an early intervention program, school-based education program, or private practice. The program should be reviewed and modified as the child's needs change over time (Weissman, 2023b). Young children who have ASD benefit from these services and caregiverslearn to implement child-responsive engagement strategies when a caregiver-coaching intervention is provided. The evidence supports combining caregiver-mediated and direct clinician-implemented interventions to maximize each child's developmental gains (Hyman et al., 2020). In a 2019 cohort study involving children in an urban EIS program, McManus and colleagues (2019) found that only 73% of referred patients initiated services, and only 43% successfully started services within the federally mandated deadline of 45 days. The researchers also concluded that one additional hour of therapy per month was associated with a 3-point functional gain on the Child Outcomes Summary score (McManus et al., 2019). Early identification, involvement in intervention, and movement toward inclusion with typical peers are all associated with positive outcomes. While some children retain the diagnosis despite all interventions, those who have milder symptoms may no longer meet the criteria as they get older (Weissman, 2023b).

No single therapy has been proven to be the most effective for ASD. In addition to varying by a child's age and developmental level, interventions differ in their theoretical approach, delivery modality, and targets. According to Hyman and colleagues (2020), the most effective behavioral and communication techniques provide structure, direction, and organization for a child and their family. While numerous behavioral interventions and treatment programs are available, certain therapies have more robust evidence supporting their efficacy (Hyman et al., 2020; Weissman, 2023b). The core features of effective ASD educational and behavioral programs include the following:

• staff-to-student ratio (1:1 or 1:2)
• individualized program tailored to meet the needs of each child
• teachers with specialized experience working with children who have ASD and a highly supportive teaching environment
• at least 25 hours per week of services
• curriculum emphasizing attention, imitation, communication, play, social interaction, regulation, and self-advocacy
• predictability and structure
• functional analysis of behavior needs
• transition planning
• family/caregiver involvement
• close monitoring, ongoing program evaluation, and adjustment based on each child's evolving needs (Weissman, 2023b)

Wong and colleagues (2015) defined two categories of evidence-based interventions: a comprehensive treatment model (CTM) and focused interventions, both of which have been widely adopted and supported by evidence-based practice guidelines (Steinbrenner et al., 2020) and the AAP (Hyman et al., 2020). These interventions can be offered in several settings (e.g., classroom, home-based, or community) and individual or group sessions. CTMs consist of a set of practices designed to achieve a broad learning or developmental impact on several core features of ASD. CTMs can address multiple therapeutic goals over a defined period. In contrast, focused interventions target a single skill or goal. These interventions are operationally defined, address specific learner outcomes, and tend to occur over a shorter period than CTMs (i.e. until the objective is achieved). Focused interventions are the key components of educational programs for children and youth who have ASD, and they may be effective in promoting skill development and communication (Hyman et al., 2020; Steinbrenner et al., 2020; Wong et al., 2015).

            Two primary evidence-based approaches used in current practice include naturalistic developmental behavioral interventions (NDBI) and applied behavior analysis (ABA). NDBI incorporates elements of ABA and developmental principles, emphasizing developmentally based learning objectives and foundational social learning skills. NDBI typically fosters a flow of social engagement patterns between a child and their provider (typically a therapist or behavioral interventionist). The goal is to promote child engagement and skill development, expanding the child's communication, social cues, and play interactions. NDBI employs turn-taking during play, child-initiated teaching episodes, and naturally occurring opportunities to engage in clear and developmentally appropriate cues (e.g., antecedents) to elicit specific behaviors and consequences (e.g., rewards/reinforcement; CDC, 2024g; Hyman et al., 2020).

Most evidence-based treatment models for ASD are based on ABA, the most well-cited and widely researched behavioral intervention for ASD. ABA was developed in the late 1960s and originally defined as "the process of applying sometimes tentative principles of behavior to the improvement of specific behaviors, and simultaneously evaluating whether or not any changes noted are indeed attributable to the process of application—and if so, to what parts of that process" (Baer et al., 1968, p. 91). Hyman and colleagues (2020) currently define ABA as "the process of systematical interventions based upon the principles of learning theory to improve socially significant behaviors to a meaningful degree, and to demonstrate that the interventions employed are responsible for the improvement in behavior" (p. 22). ABA is offered to young children who have EIS and is used among older children, adolescents, and adult populations. ABA employs an operant conditioning model, a method of learning that uses rewards and punishments for behavior. It encourages positive behavior through rewards and discourages negative or unwanted behavior by ignoring it. This method seeks to associate a behavior with a direct consequence (either positive or negative) for the specific behavior (Hyman et al., 2020; Weissman, 2023a).

In contrast to NDBI, ABA promotes a more straightforward, decontextualized, and highly structured approach. ABA aims to help improve the child's communication, attention, focus, memory, and academics while decreasing specific problem behaviors. ABA is flexible: It can be performed in any setting as an individualized, one-on-one treatment or within a group. It typically occurs for 25 to 40 hours per week and can last for 1 to 3 years. It breaks the learning process down into the ABCs: antecedent, behavior, and consequence (Hyman et al., 2020). There are various forms of ABA, and some prime examples are outlined below (Autism Speaks, n.d.; CDC, 2024g; NICHD, 2021a; Weissman, 2023a):

• Discrete Trial Training is a teaching style that uses a series of trials to teach specific steps of a desired behavior or response. Lessons are separated into simple fragments, and positive reinforcement is used to reward appropriate answers and behaviors. Incorrect answers are ignored. This is the most structured form of intensive behavior therapy.
• Early Intensive Behavioral Intervention is a highly structured teaching approach that targets building positive behaviors (e.g., social communication) and reducing unwanted behaviors (e.g., self-injury, tantrums, and aggression).
• Early Start Denver Model focuses on play to build positive relationships and joint activities to help children expand their language, social, and cognitive abilities.
• Pivotal Response Training attempts to increase a child's motivation to learn, monitor their behavior, and initiate communication with others through positive reinforcement. It targets "pivotal areas" such as the initiation of social interactions and self-management. Pivotal Response Training is play-based and child-led and can be implemented in the child's environment at home rather than in a clinical setting.
• Verbal Behavior Intervention Therapy focuses on teaching verbal communication skills. It helps children connect words with their use or purpose to help children understand why we need to use words and how they can be helpful.
• Positive Behavior Support seeks to determine the cause of negative or unwanted behaviors, change the environment, and then teach skills regarding the correct or desired behavior as a replacement.

In addition to NDBI and ABA, other evidence-based interventions for ASD are described in Table 8.

Table 8

Evidence-Based Behavioral Interventions

Intervention	Description
Picture exchange communication system (PECS)	PECS is often used for very young children with significant verbal support needs. It teaches them to use pictures as aids for communicating wants and needs.
Developmental, individual differences, relationship-based approach (DIR)	Also referred to as "floor time," DIR focuses on each child's emotional and relational development (i.e., their feelings and relationships with caregivers) and how they regulate their sensory perception of sights, sounds, and smells. Since many children who have ASD experience sensory reactivity, the key is to get on the floor and play with children at their level, allowing them to take the lead initially and then guiding them toward six milestones: self-regulation and interest in the world, intimacy and engagement in relationships, two-way communication, complex communication, emotional ideas, and emotional thinking.
Treatment and education of autism and related communication-handicapped children (TEACCH)	TEACCH was developed in the 1960s at the University of North Carolina. It uses visual cues to break skills and behaviors into more manageable tasks. It is primarily a classroom-based strategy that uses a child's innate strengths (visual information processing) to target their challenges (social communication, attention, and/or executive functioning). For example, picture cards teach a child how to brush their teeth by highlighting the information in small steps. It requires organizational support, visual and written information, and structured support for social communication.
Relationship development intervention (RDI)	RDI is a family-based therapy that aims to build social and emotional skills by training a child's caregiversto be their primary therapists and teaches dynamic intelligence (mental flexibility).
Cognitive-behavioral therapy (CBT)	CBT focuses on the connection between a child's thoughts, feelings, and behaviors. It can be beneficial for anxiety, especially in social situations.

(Autism Speaks, n.d.; CDC, 2024g; Steinbrenner et al., 2020; Weissman, 2023a)

Family Involvement in Behavioral Therapy

Much of the success experienced by patients who have ASD relies on the skills, capabilities, education, investment, and training of their caregiversand family unit. A growing body of evidence reveals that focused interventions delivered by trained caregivers are an important component of the treatment program. Families should be involved in the selection of intervention approaches and participate in all educational and therapeutic decisions. By law, students who have ASD must receive an appropriate educational program, although it may not include all the components desired by the family (Eidson et al., 2020). According to Hyman and colleagues (2020), caregiver management training consists of two categories: caregiver support and caregiver-mediated interventions. Caregiver support interventions are knowledge-focused, indirectly benefit the child, and include care coordination and psychoeducation. Caregiver-mediated interventions are technique-focused and directly benefit the child. They focus on the core needs of ASD and are often based on ABA principles. Studies demonstrate that caregiver-mediated interventions significantly impact both caregiver and child behaviors (Tabatabaei et al., 2020).

Pharmacological Therapy

While medications cannot treat or cure ASD, they may be used to manage medical or mental health comorbidities, minimize symptoms, and maximize an individual's abilities. The Autism Speaks Autism Treatment Network (ATN) consists of hospitals, physicians, researchers, and families across the US and Canada, supported by a cooperative agreement with the US Department of Health & Human Services. The ATN (2012) developed a toolkit for families and children who have ASD and are on medications to help manage challenging behaviors or emotional issues. This toolkit focuses on certain categories of medicines that are common but can be broadly applied to most other medicines. While medications can help some children, medication is not suitable for everyone. Pharmacologic agents should only be started after behavioral and educational interventions are in place, maximized, and not producing the desired response (Weissman & Harris, 2024). Once medication therapy is initiated, ongoing behavioral therapies are still essential. Despite these recommendations, no formal guidelines preclude the early use of medication therapy. Medication use should be based on shared decision-making between the prescriber, patient, and family. The medication recommended will depend on the child's primary needs, as each medication treats different targets. Before prescribing, APRNs should be transparent with families about treatment goals and the possible risks and benefits. Three main factors to consider when choosing an agent are the likelihood of improving the symptom or behavior, potential side effects, and practical considerations (e.g., dose schedule, cost, laboratory monitoring, and formulations). Medications should be started at the lowest dose and increased more slowly, as individuals who have ASD have a higher risk of adverse effects. This section will review some of the most prescribed medications for ASD, but it is not a comprehensive list (Weissman & Harris, 2024).

 

SGAs

Risperidone (Risperdal) and aripiprazole (Abilify) are the only US Food & Drug Administration (FDA)-approved medications for the treatment of disruptive and maladaptive behaviors associated with ASD (Weissman & Harris, 2024). While both medications are most commonly used to treat schizophrenia, they work differently. Risperidone (Risperdal) antagonizes dopamine and serotonin receptors in the brain, rebalancing dopamine and serotonin levels in the brain to improve thinking, mood, and behavior (National Alliance on Mental Illness [NAMI], 2024c). Aripiprazole (Abilify) functions as a partial dopamine and serotonin 5-HT1A agonist and 5-HT2A antagonist, rebalancing dopamine and serotonin to improve mood, thinking, and behavior (NAMI, 2024a). Both medications are available in oral disintegrating tablet formulation, which is beneficial in children who may not be able to swallow pills or who may try to conceal tablets in their mouth or dispose of them (Jibson, 2024).

Risperidone (Risperdal) is indicated to treat irritability associated with ASD for children and adolescents aged 5 to 18 years. The indications for use include aggression, temper, self-injurious behavior, and quick-changing moods associated with ASD. Risperidone (Risperdal) dosing is weight-based and prescribed at a starting dose of 0.25 mg/day for patients weighing 33 to 44 pounds (15 to 20 kilograms) and 0.5 mg/day for patients weighing 44 pounds (20 kilograms) or more. This dose may be doubled after 4 days. After this, dosing increases from 0.25 to 0.5 milligrams at 2-week intervals are indicated if sufficient clinical response is not achieved. The effective dose range is 0.5 to 3 mg/day, but the dose should be individualized to the response and tolerability of each patient. The total dose can be administered once or twice daily in divided doses. Once a sufficient clinical response is achieved and maintained, consideration should be given to lowering the dose gradually to achieve the optimal balance of efficacy, safety, and side effects. Dose adjustment is required for patients with creatinine clearance below 60 mL/min or severe hepatic impairment (Lexidrug, 2024b). The most common side effects include somnolence, increased appetite, fatigue, cold symptoms, weight gain, vomiting, urinary incontinence, increased saliva, tremor, constipation, anxiety, and dizziness. APRNs should counsel patients and caregiversthat somnolence has an early onset with a peak incidence during the first 2 weeks of treatment and a median duration of 16 days. Persistent somnolence can be managed by administering a once-daily dose at bedtime, giving half the daily dose twice daily (instead of once daily), or reducing the dose (FDA, 2009).

Aripiprazole (Abilify) is indicated to treat irritability associated with ASD for children and adolescents aged 6 to 17 years. The starting dose of aripiprazole (Abilify) is 2 mg/day, the recommended dose ranges from 5 to 10 mg/day, and the maximum daily dose is 15 mg/day. According to the prescribing guidelines, initial aripiprazole (Abilify) dosing adjustments can be done at day 7 up to 5 mg/day, followed by 5 mg/day increases at intervals of no less than 1 week (Lexidrug, 2024a). Patients should be routinely reassessed to determine their ongoing need for maintenance treatment. Possible side effects of aripiprazole (Abilify) include changes in blood sugar and cholesterol, sleepiness/sedation, vomiting, nausea, weight gain, dizziness, insomnia, anxiety, constipation, headache, and restlessness (FDA, 2016; NAMI, 2024a). There is a warning from the FDA associating aripiprazole (Ability) use with compulsive or uncontrollable urges to shop, binge eat, gamble, and participate in high-risk sexual behaviors. These urges ceased with discontinuation of the medication or dose reduction (NAMI, 2024a). While both risperidone (Risperdal) and aripiprazole (Abilify) have black box warnings for older adults who have dementia, aripiprazole (Abilify) has a black box warning for suicidal thoughts or actions in children, adolescents, and young adults (NAMI, 2024a, 2024c).

Some patients taking risperidone (Risperdal) and aripiprazole (Abilify) may experience extrapyramidal symptoms (e.g., restlessness, stiffness, tremor) and tardive dyskinesia (TD; uncontrollable jerky or slow movements such as tongue rolling or chewing). TD typically develops as a side effect with long-term use of these medications. However, the risk of TD is lower with these SGAs compared to older ones, such as haloperidol (Haldol). The APRN should screen all patients taking a first- or second-generation antipsychotic for TD using the Unexpected Involuntary Movement Scale (NAMI, 2024a, 2024c). Recommendations are for yearly screening or biannual screening for those at high risk, including older adults and patients who have prominent extrapyramidal symptoms (Jibson, 2024). This scale is a 14-item assessment that evaluates the movement of the head, dentition, neck, limb, and trunk on a rating from 0 (absent movement) to 4 (severe movement; Liang, 2023). Serious but rare side effects include elevated prolactin and sudden cardiac death due to arrhythmia. These atypical antipsychotics can also affect temperature regulation, making it vital that the APRN educates patients and families on the importance of staying hydrated. SGAs are also associated with an increased risk of metabolic syndrome (e.g., weight gain, high blood sugar, and high cholesterol; NAMI, 2024a, 2024c).

While only two medications are FDA-approved for ASD-related irritability, several other medications are used off-label to manage depression, anxiety, ADHD, or OCD symptoms (Weissman & Harris, 2024). FDA approval means that the FDA has determined the benefits of a medication to outweigh the potential risks for its intended use. It does not mean that the medication does not have side effects. Once the FDA has approved a medication, healthcare providers may prescribe this medication to treat other conditions. It may be prescribed because there is not an FDA-approved medication for that specific condition or the FDA-approved medications (e.g., risperidone [Risperdal] and aripiprazole [Abilify]) did not achieve the intended benefit for the patient. This is referred to as "off-label" use (FDA, 2018b). There are additional off-label pharmacologic interventions for individuals who have ASD. The APRN should identify the most concerning behavior or the behavior that is impairing function the most when considering treatment with other pharmacologic agents.

Stimulants

Stimulant medications can reduce hyperactivity symptoms, improve focus, extend attention span, or manage impulsive behaviors. Medications for ADHD can effectively help diminish impulsivity and hyperactivity symptoms when they coexist with ASD (Weissman & Harris, 2024). Stimulants heighten the central nervous system (CNS) response, typically by increasing catecholamine levels in the brain. Catecholamines refer to a group of neurotransmitters that are endogenously released into the bloodstream in response to stress. The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine (Farzam et al., 2023). Some of the most used stimulant medications in children who have ASD include the following:

• methylphenidate (Ritalin, Concerta)
• dexmethylphenidate (Focalin)
• dextroamphetamine/amphetamine (Adderall)
• dextroamphetamine (Dexedrine)
• lisdexamfetamine (Vyvanse; Weissman & Harris, 2024)

Methylphenidate (Ritalin) is commonly the first choice because it is better tolerated despite the potential for amphetamine-based stimulants being more effective. Individuals who have ASD have a similar side effect profile with stimulants. However, like other medications, side effects are typically more frequent (Weissman & Harris, 2024). Stimulants can cause side effects such as sleep disturbances (especially difficulty falling asleep), anorexia, irritability, and emotional outbursts. Less commonly, patients may experience involuntary tics, depression, anxiety, headaches, repetitive behaviors and thoughts, diarrhea, or social withdrawal. In addition, CNS stimulants carry a risk for serious cardiovascular reactions, including changes in heart rate, unexpected cardiac rhythm, and increased blood pressure. Sudden death, stroke, and myocardial infarction have been reported in adults taking CNS stimulants at the recommended doses. Furthermore, these medications can induce psychosis and paranoia or exacerbate behavioral disturbance and thought disorder for patients who have preexisting psychotic disorders (FDA, 2019; Weissman & Harris, 2024).

Stimulants have a boxed warning regarding their high potential for misuse and dependence. Prescribers must assess the risk of misuse before prescribing and monitor patients for signs of abuse and dependence while on therapy. Misuse is characterized by impaired control over drug use despite harm and cravings. The most common signs and symptoms of stimulant misuse include an increased heart rate, sweating, dilated pupils, hyperactivity, restlessness, insomnia, loss of coordination, tremors, flushed skin, and vomiting. In rare cases, anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed (Paulus, 2023). Tolerance refers to a state of adaptation in which exposure to a drug reduces the drug's desired and/or undesired effects; it can occur during chronic therapy with these medications. Physical dependence occurs when the abrupt cessation of the drug produces withdrawal symptoms. Finally, stimulants have been associated with acute overdose, which can be fatal as the CNS is overstimulated. Symptoms of overdose can include GI distress (e.g., nausea/vomiting), restlessness, agitation, anxiety, tremors, hyperreflexia (overactive reflexes), muscle twitching, convulsions, euphoria, confusion, hallucinations, delirium, sweating, palpitations, cardiac arrhythmias, hypotension, tachypnea, mydriasis (pupil dilation), rhabdomyolysis (breakdown of muscle tissue causing the leakage of damaging proteins into the blood), and coma (Farzam et al., 2023; FDA, 2019).

 

Antidepressants

Antidepressants may be prescribed to manage depression and other conditions such as anxiety, pain, and insomnia. Most FDA-approved prescription medications for depression target three neurotransmitters: serotonin, norepinephrine, and dopamine. SSRIs work by increasing serotonin levels and are usually the safest initial choice of antidepressants because they tend to cause the fewest side effects. The most common medications prescribed for ASD include the following SSRIs:

• fluoxetine (Prozac)
• fluvoxamine (Luvox)
• sertraline (Zoloft)
• paroxetine (Paxil)
• citalopram (Celexa)
• escitalopram (Lexapro; National Institute of Mental Health [NIMH], 2023; Weissman & Harris, 2024)

SSRIs are used first-line for anxiety in individuals who have ASD and are used for the treatment of depressive symptoms, repetitive behaviors, rigidity, and mood lability (Weissman & Harris, 2024). Antidepressants usually take 4 to 8 weeks to achieve their optimal effect. Symptoms pertaining to sleep, appetite, and concentration often improve before a notable change in mood. Due to their side effect profiles, most antidepressants need to be tapered up slowly when starting therapy and tapered down gradually when stopping treatment. If stopped abruptly, some antidepressants pose a risk for withdrawal-like symptoms such as dizziness, headache, flu-like syndrome (tiredness, chills, muscle aches), agitation, irritability, insomnia, nightmares, diarrhea, and nausea. The most common side effects include GI problems (nausea, vomiting, constipation), headaches, difficulty falling asleep, sleepiness, and weight gain. All patients taking SSRIs are at risk for an adverse drug reaction called serotonin syndrome, characterized by agitation, anxiety, confusion, high fever, sweating, tremors, lack of coordination, dangerous fluctuations in blood pressure, and rapid heart rate. Serotonin syndrome is a potentially life-threatening condition for which patients must seek immediate medical attention. While antidepressants typically do not require routine laboratory monitoring or medication levels, prescribers should remain alert to the potential side effects and adverse effects outlined above (NIMH, 2023). When using SSRIs in individuals who have ASD, there may also be an increased risk of behavior activation (e.g., agitation, impulsivity, and silliness; Weissman & Harris, 2024).

Antidepressants that target the neurotransmitter norepinephrine may be used to treat ADHD, but they are not FDA-approved for this indication and are considered off-label. Bupropion (Wellbutrin) is a norepinephrine and dopamine reuptake inhibitor that helps improve concentration and focus and reduces hyperactivity. It is regularly prescribed for ADHD and is another agent used to treat anxiety in individuals who have ASD if SSRIs do not achieve the intended benefit (NAMI, 2024b; Weissman & Harris, 2024). It may also be used as an adjunct therapy after SSRIs for restrictive and repetitive behaviors (Weissman & Harris, 2024). Since bupropion (Wellbutrin) does not influence serotonin, it works differently than the antidepressants outlined above. The most common side effects include headaches, weight loss, dry mouth, insomnia, nausea, dizziness, constipation, tachycardia, and sore throat. These side effects typically improve over the first 1 to 2 weeks on the medication. Rare but potentially serious side effects affecting fewer than 10% of patients include skin rash, sweating, ringing in the ears (tinnitus), stomach pain, muscle pain, thought disturbances, anxiety, or angle-closure glaucoma (e.g., eye pain, changes in vision, swelling or redness in or around the eye). Bupropion (Wellbutrin) is also associated with an increased risk for seizures in people susceptible to them. This is particularly important for children who have ASD due to the high prevalence of coexisting seizure disorders. Thus, it is recommended that bupropion (Wellbutrin) is not prescribed to children who have coexisting epilepsy or those who have experienced recurrent seizures (NAMI, 2024b).

In 2004, the FDA required a warning to be printed on the labels of all antidepressant medications regarding the risk for increased suicidality among children and adolescents taking these medications. A few years later, the warning was expanded to all young adults, especially those under 25, stating that these individuals may experience increased suicidal thoughts or behaviors during the first few weeks on antidepressants and warning clinicians to monitor patients for this effect. The FDA also requires manufacturers to provide a Patient Medication Guide to patients (or caregivers) to advise them of the risks of suicide and precautions that can be taken. Furthermore, prescribers are advised to ask patients about suicidal thoughts before prescribing antidepressants to young people (FDA, 2018a). APRNs should counsel families on the heightened importance of monitoring for these symptoms in patients who have ASD, particularly those with significant communication needs. Table 9 lists the points that must be included in the boxed warning.

Table 9

FDA Antidepressants Boxed Warning Points

Antidepressants increase the risk of suicidal thinking and behavior (suicidality) for children and adolescents who have major depressive disorder and other psychiatric disorders.

Anyone considering prescribing an antidepressant to a child or adolescent for any clinical use must balance the risk of increased suicidality with the clinical need.

Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior.

Families and caregivers should be advised to observe the patient closely and communicate with the prescriber.

Antidepressants must include a statement regarding whether the particular medication is approved for any pediatric indication(s) and, if so, which one(s).

 (FDA, 2018a)

Anticonvulsants

Anticonvulsants, also referred to as antiepileptic drugs (AEDs), are first-line treatments for seizures. To date, no AED has been explicitly studied regarding its efficacy in treating seizures in ASD (Frye et al., n.d.). Treatment of seizures in individuals who have ASD is similar to that of individuals who do not have ASD. AEDs such as lamotrigine (Lamictal) are prescribed off-label for mood stabilization (Weissman & Harris, 2024). Some of the most prescribed anticonvulsants for children include the following:

• carbamazepine (Tegretol)
• valproic acid (Depakote)
• lamotrigine (Lamictal)
• oxcarbazepine (Trileptal)
• topiramate (Topamax; Frye et al., n.d.; Wilfong, 2022)

 

AED dosing for children is weight-based, and doses are titrated slowly based on tolerance and response. Patients and their caregivers should be counseled on the importance of taking medications at the same time every day. Consistency is vital to maintaining the therapeutic blood concentration of the medication. Patients and caregivers should be reminded never to stop the medication without the prescriber's awareness and direction, as most options must be tapered to avoid withdrawal symptoms or increased seizure activity. Adverse drug effects can contribute significantly to impaired quality of life, and improved quality of life is a goal of treatment in individuals who have ASD. Common side effects of most anticonvulsants include drowsiness, dizziness, diplopia, and imbalance. Additional side effects are more specific to each medication, which are summarized in Table 10.

Table 10

Systemic and Neurologic Side Effects of Antiseizure Medications

Medication	Side Effects
Carbamazepine (Tegretol)	Rash, pruritis, hyponatremia, diarrhea, vomiting, nausea, lethargy, headache
Lamotrigine (Lamictal)	Nausea, rash, tremor
Oxcarbazepine (Trileptal)	Rash, hyponatremia, sedation, headache, vertigo, ataxia
Topiramate (Topamax)	Weight loss, fatigue, paresthesia, nervousness, confusion, depression, anorexia, anxiety, mood problems, tremor, difficulty concentrating
Valproic acid (Depakote)	Weight gain, easy bruising, hair loss, nausea, vomiting, tremor

(Wilfong, 2022)

Complementary and Alternative Medicine 

Complementary and alternative medicine (CAM) treatments are non-mainstreamed practices implemented in place of conventional options or alongside evidence-based treatments. Many CAM treatments have little or no scientific evidence supporting their efficacy but are widely available and used. CAM therapies are often considered attractive options for families because they focus on support needs (CDC, 2024g). It is likely that patients and their families will ask about CAM therapies that other families, celebrities, or the internet promote. Between 28% and 74% of children who have ASD receive at least one CAM treatment. According to Hyman and colleagues (2020), CAM therapies can be grouped into three major categories as follows:

• natural products (e.g., herbs, vitamins and minerals, and probiotics)
• mind and body practices (e.g., yoga, chiropractic care, massage, acupuncture, progressive relaxation, and guided imagery)
• other therapies (e.g., traditional medicine and naturopathy)

 

The National Center for Complementary and Integrative Health (NCCIH) maintains a website regarding novel CAM therapies for patients who have ASD. The NCCIH (2024) acknowledges the lack of high-quality research on CAM treatments for ASD and makes the following statements and recommendations regarding current CAM approaches:

• There is no scientific evidence that chelation therapy, hyperbaric oxygen, antifungal agents, or secretin helps patients who have ASD. On the contrary, it can even be harmful.
• There is unclear evidence to support improved health and well-being in individuals who have autism with the use of oxytocin, omega-3 fatty acids, acupuncture, or massage therapy. These therapies should not be used in place of conventional treatments.
• Art, yoga, animal-assisted acupuncture, massage, and exercise-based therapies may improve hypersensitivity, anxiety, social skills, and mental health, yet further research is needed to establish benefits in patients who have ASD.
• Low-dose melatonin may improve sleep in individuals who have ASD. However, adverse effects and long-term safety should be discussed with the individual's healthcare provider.
• Mindfulness-based practices are an emerging area in individuals who have ASD, as they may be helpful in improving emotional regulation.
• Specific dietary interventions have mixed results in research, and these should be individually discussed with the health care team to ensure nutritional needs are met.
• Cannabis use has limited research and no guidelines for individuals who have ASD. However, it may improve insomnia, epilepsy, hyperactivity, and chronic pain (NCCIH, 2024).

Music therapy may positively affect social interaction, communication, and behavioral skills in children who have ASD. According to Hyman and colleagues (2020), there is limited and conflicting evidence regarding the efficacy of other widely used CAM therapies, such as massage, chiropractic care, yoga, and equine-assisted therapy. However, unlike some of the CAM interventions described above, these options have little to no potential adverse effects. While further research is necessary to establish their clinical utility and efficacy, these interventions may be beneficial adjunct therapies for children who have ASD, mainly when used with evidence-based treatments. Numerous other CAM therapies have not been reviewed in this section. Regardless of the treatment, APRNs must encourage caregiversto discuss all therapeutic options with their child's healthcare provider before starting (CDC, 2024g; NCCIH, 2021, 2024).

 

Dietary Interventions

Dietary interventions are often used to ameliorate the core needs and problem behaviors of ASD. Dietary adjustments are perceived as beneficial by many caregiversbecause they are considered natural. The most common nutritional change is the elimination of dairy, sugar, gluten, and casein. To date, clinical trials have not demonstrated statistically significant treatment effects with these dietary adjustments (Hyman et al., 2020). The impact of novel diets, such as the ketogenic diet (which causes the body to break down fats instead of carbohydrates), is not fully understood. The ketogenic diet has been marketed toward controlling seizures associated with ASD, but there is minimal data that this high-fat, low-carbohydrate diet is advantageous. Evidence has also demonstrated the side effects and health consequences of ketogenic diets in children, such as constipation, vomiting, lack of energy, hunger, hyperuricemia, hyperlipidemia, and kidney stones. According to Li and colleagues (2021), the most severe side effect of the ketogenic diet in children is the suppression of physical development and impaired growth. While specific dietary changes may help improve problem behaviors in some children who have ASD, their nutritional needs must be monitored to avoid harmful health consequences, especially dangerous vitamin, mineral, and nutrient deficiencies or growth retardation. Nutritional counseling is strongly recommended for caregiverswho want their child to try a special diet to manage ASD-related needs (Li et al., 2021; NCCIH, 2024).

 

Supplements

Dietary supplements are readily available over the counter and represent various substances ranging from vitamins and minerals to enzymes, probiotics, and botanicals. These are used for diverse indications, such as managing symptoms or enhancing wellness, and are available in various forms (e.g., pills, gummies, powders, bars, and drinks). Most supplements and herbal preparations have not undergone rigorous scientific testing for safety or effectiveness. While the FDA regulates prescription and other over-the-counter medications to ensure their safety and efficacy, dietary supplements are not subjected to the same scrutiny and oversight. The lack of FDA oversight and regulation of these agents poses concerns regarding their consistency, ingredient purity, and safety profiles. They often contain hidden ingredients that may not be appropriate for all consumers (FDA, 2024; NCCIH, 2024).

Melatonin is the most researched CAM, with the most consistent results that are favorable in safety and efficacy (Zhukova et al., 2020). It is an option for individuals who have ASD who have difficulty falling asleep alongside other interventions such as sleep hygiene. The starting dose is 0.5 to 1 milligram, depending on age, increasing in 1-milligram increments up to 6 mg/day. It should be taken 30 to 60 minutes before bed. Side effects of melatonin may include nocturnal enuresis, difficulty waking, sleepiness, dizziness, and headache (Weissman & Harris, 2024).

Additional popular dietary and vitamin supplements for ASD include omega-3 fatty acids, vitamin D, magnesium, and vitamin B₆. Despite their widespread use, there is limited high-quality research regarding the efficacy of these agents for children who have ASD (Hyman et al., 2020; NCCIH, 2021, 2024).

No conclusive evidence demonstrates that children or adults who have ASD require a higher vitamin intake than the daily recommendations for the general population. Some vitamins and dietary supplements can cause dangerous side effects and interactions when taken with other supplements or prescription medications. Taking too much of a supplement or vitamin or substituting supplements for prescription medicines can be harmful, causing severe side effects and dangerous medication interactions; in some cases, the consequences can even be life-threatening. Furthermore, the long-term risks of high-dose vitamin supplementation have not been studied in children who have ASD. APRNs should counsel caregiverson the safety hazards of initiating unproven therapies without speaking to their child's healthcare provider (CDC, 2024g; Hyman et al., 2020; NCCIH, 2024).

For more information on dietary supplements, refer to the Dietary Supplements NursingCE course.

 

Caregiver Education and Resources

It is challenging to predict the outcomes for children who have ASD, especially those younger than 3 years. Some children will sustain the diagnosis, whereas others may no longer meet the diagnostic criteria for ASD as they age. Typically, children who no longer meet the diagnostic criteria for ASD continue to demonstrate residual social, communication, and/or behavioral needs during adulthood. APRNs serve central roles in educating caregiverson the signs of ASD to facilitate early recognition and intervention (Hyman et al., 2020; Shulman et al., 2019). Additionally, having a child who has ASD has significant impacts on the family unit, including more stress and increased costs. Peer support is reported to improve stress and increase positive perceptions. It is considered best practice to give families resources for family support groups at the time of an ASD diagnosis (Hyman et al., 2020).

APRNs should use each routine well-child health care visit as an opportunity to educate caregiverson the early warning signs of ASD. Caregivers are encouraged to screen milestones from age 2 months to 5 years of age and act early if they have concerns (CDC, 2024d). The CDC (2024g) offers a free, user-friendly Milestone Tracker app and other resources to make it easy for caregiversto track, support, and discuss their young child's development with their child's healthcare provider (https://www.cdc.gov/ncbddd/actearly/index.html). The ATN (n.d.) has compiled a decision aid for caregivers to help them assess their personal beliefs on using medications for challenging ASD-related behaviors, providing information regarding the possible risks and benefits of different agents. This resource promotes collaboration with the child's healthcare provider to choose a treatment that matches their personal needs, values, and treatment goals (ATN, n.d.).

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