Version May 2024
INTRODUCTION — Autism spectrum disorder (ASD) is a biologically based neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction and restricted, repetitive patterns of behavior, interests, and activities.
The discussion that follows will focus on complementary and alternative therapies for ASD. Related topics are presented separately:
●(See "Autism spectrum disorder in children and adolescents: Clinical features".)
●(See "Autism spectrum disorder in children and adolescents: Evaluation and diagnosis".)
●(See "Autism spectrum disorder in children and adolescents: Overview of management".)
●(See "Autism spectrum disorder in children and adolescents: Behavioral and educational interventions".)
●(See "Autism spectrum disorder in children and adolescents: Pharmacologic interventions".)
DEFINITION OF CAM — Complementary and alternative medicine (CAM) therapies, as defined by the National Center for Complementary and Alternative Medicine, are "a group of diverse medical and healthcare systems, practices, and products that are not generally considered to be part of conventional medicine" [1].
Alternative therapies are those that are used instead of conventional therapies. Complementary therapies are those that are used in conjunction with conventional therapies. The combination of conventional and complementary techniques that have some supportive evidence is often called "integrative medicine" [2]. Some of the interventions originally considered to be complementary may become part of conventional practice when there is scientific evidence to support their use. (See "Complementary and integrative health in pediatrics", section on 'Definitions'.)
Conventional therapies for ASD include behavioral therapies (eg, intensive behavioral therapy such as applied behavioral analysis). They have been shown to be effective in systematic reviews of randomized and observational studies and are discussed separately. (See "Autism spectrum disorder in children and adolescents: Overview of management" and "Autism spectrum disorder in children and adolescents: Behavioral and educational interventions", section on 'Intensive behavioral interventions'.)
PREVALENCE OF USE IN ASD — Complementary and alternative medicine (CAM) is commonly used in children with special health care needs. In large studies of children with ASD, 27 to 88 percent of families report having used CAM therapies of any type, and 17 to 25 percent used special diets [3-7]. Rates tend to be higher in children with more severe forms of ASD, those diagnosed at an earlier age, those who are hyperactive or irritable, and those with gastrointestinal symptoms, food allergies, or seizures [3,8]. The types of therapies are diverse (table 1). Vitamins, supplements, special diets, and body-based practices (eg, massage therapy, chiropractic) tend to be used most commonly [2,5].
RATIONALE FOR USE IN ASD — ASD is a neurodevelopmental disorder with an incompletely understood etiology. Although core symptoms may improve over time with appropriate therapy, there is no known cure. Many caregivers of children with ASD seek both conventional and complementary and alternative (CAM) therapies as part of the process of understanding and accepting the diagnosis. (See "Autism spectrum disorder in children and adolescents: Overview of management" and "Autism spectrum disorder (ASD) in children and adolescents: Terminology, epidemiology, and pathogenesis", section on 'Pathogenesis'.)
Some caregivers choose CAM due to perceived lack of efficacy of conventional treatments for ASD and in the hope of finding a cure, while others use CAM in addition to conventional treatments as they want to do everything possible to help their child [2,9]. Caregivers may choose CAM therapies to treat a variety of symptoms, including the core symptoms of ASD (eg, deficits in social communication and interaction and restricted, repetitive patterns of behavior, interests, and activities), inattention, gastrointestinal symptoms, and sleep disturbance; to promote a healthy lifestyle [10]; or out of concerns about safety or side effects of conventional allopathic therapies such as prescribed medications [11]. Some treatments are undertaken to address a biologic condition that the caregiver believes contributes to the pathogenesis of ASD, whether or not there is scientific evidence to support the hypothesis. Some of these biologic hypotheses propose that the development of ASD is related to [12]:
●Gastrointestinal abnormalities, such as dysbiosis (abnormalities of microflora) or "leaky gut," prompting the use of secretin, antifungal agents, probiotics, etc (see 'Secretin' below and 'Antimicrobial agents' below and 'Probiotics' below)
●Food sensitivities and allergies, prompting the use of special diets, such as the gluten-free and/or casein-free diet (see 'Gluten-free casein-free diet' below)
●Autoimmunity, prompting the use of immunotherapy (see 'Intravenous immunoglobulin' below)
●Metabolic abnormalities (eg, in glutathione synthesis, sulfation, folate metabolism), prompting the use of antioxidants [13-15] (see 'Sulforaphane' below and 'Other interventions' below)
●Heavy metal toxicity, especially mercury, prompting the use of chelation therapy (see 'Chelation' below)
●Nutritional imbalances, prompting the use of nutritional supplements (eg, omega-3 fatty acids, vitamins) (see 'Omega-3 fatty acids' below and 'Vitamin B6 and magnesium' below and 'Other interventions' below)
●Inflammation [16] (see 'Sulforaphane' below)
CLINICIAN GUIDANCE
General principles — Decisions about therapies for children with ASD should integrate clinical expertise, patient and caregiver values and preferences, and the best evidence of efficacy [2,10,17-20]. Although complementary and alternative (CAM) therapies are frequently used by families of children with ASD, few such therapies have been proven effective (or ineffective) or safe in controlled trials. Despite the lack of high-quality evidence, families use CAM, and certain CAM therapies are recommended by some clinicians [21].
It is important to ask caregivers of children with ASD specifically about the use of CAM therapies; they may not volunteer this information and may not realize that CAM therapies can have side effects and potential interactions with prescription medications [5,6,22]. General recommendations for counseling caregivers who choose CAM therapies for their children are provided separately (table 2). (See "Complementary and integrative health in pediatrics", section on 'Discussing complementary therapies with patients and families'.)
Evaluation of evidence — Clinicians should evaluate the evidence for all treatments, both conventional and CAM [2,10]. When evaluating the merits of a study, look for a homogeneous case definition, control for potential confounding variables, consistent dosing, appropriate comparison group, appropriate blinding (if applicable), valid outcome measure(s), and adequate sample size [23]. (See "Evidence-based medicine".)
The natural history of ASD, effects of other interventions (eg, conventional educational or behavioral interventions), and the placebo effect also must be taken into account [23-25]. Patients with chronic conditions with unclear pathophysiology, fluctuating courses, subjective symptoms, and few effective evidence-based treatments (such as ASD) are most vulnerable to the placebo effect.
In the hierarchy of evidence, randomized, blinded, placebo-controlled studies provide the highest-quality evidence. However, it is often difficult to perform such studies in children with ASD. Thus, much of the evidence for both conventional and CAM therapies comes from cohort studies, case-control studies, and case reports. Choosing an appropriate outcome measure is another challenge in the evaluation of interventions for ASD given the heterogeneity of presentations within the autism spectrum. Instruments that are typically used for diagnosis may not demonstrate incremental improvements in core deficits.
Potential harms — CAM therapies may compete with validated treatments for time, effort, and financial resources. There are few data about the adverse effects of CAM therapies. The magnitude of risk for hypersensitivity, systemic toxicity, and/or topical toxicity is not known. Nutritional supplements (eg, omega-3 fatty acids, vitamin B6, magnesium) are classified as foods rather than drugs. As such, they are subject to different regulations and quality controls. The potential presence of contaminants and interactions of these supplements with prescription drugs have not been studied systematically.
Counseling caregivers — Medical practitioners play an essential role in helping caregivers evaluate information regarding CAM for children with ASD. Although caregivers of children with ASD may seek CAM therapies, they also value the recommendations of their health care providers [11]. However, patients/caregivers often do not disclose the use of CAM to clinicians, so it is important that clinicians ask specifically about CAM therapies. (See "Complementary and integrative health in pediatrics", section on 'Relationship between integrative and mainstream medicine'.)
It is important for clinicians who care for children with ASD to know about CAM therapies and provide balanced information and advice about the potential benefits and risks [26]. Many caregivers use more than one treatment [27]. When counseling caregivers who are considering the use of CAM therapies that lack supportive data, the importance of using only one new therapy at a time and collecting objective outcome data should be emphasized.
Healthy lifestyle — A healthy lifestyle is encouraged for children with ASD, as for all children. This includes a healthy diet (including adequate intake of essential nutrients), regular exercise, adequate sleep, management of stress, social support, and avoidance of neurotoxins [10]. In a randomized crossover study, a seven-week aerobic cycling program (using virtual-reality exergaming stationary bicycles) was associated with improved self-regulation and classroom functioning in 103 children with behavioral health disorders (including approximately 40 percent with ASD) [28].
Vitamin D supplementation to meet daily requirements may be necessary in children with inadequate intake of vitamin D [29]. However, evidence that vitamin D supplementation improves the core symptoms of ASD is lacking [30]. (See "Dietary recommendations for toddlers and preschool and school-age children" and "Vitamin D insufficiency and deficiency in children and adolescents" and 'Unknown benefit, low risk' below.)
CLASSIFICATION ACCORDING TO BENEFITS AND RISKS — Evaluation of complementary and alternative (CAM) interventions for the core symptoms of ASD is an active area of investigation. However, few CAM therapies have been proven effective/ineffective or safe as part of well-designed randomized controlled trials (eg, adequate sample size and blinding, use of appropriate validated outcome measures, adequate duration). Given the uncertainty, the clinician and caregivers must weigh the potential benefits and risks, including competition with validated treatment for time, effort, and financial resources. (See 'Potential harms' above.)
Our recommendations are generally consistent with those of the American Academy of Pediatrics [26], National Institute of Health and Care Excellence [31], the Scottish Intercollegiate Guidelines [32], and the Technical Expert Panel (a large multidisciplinary group consisting of experts in psychology, developmental pediatrics, child psychiatry, and education, and parents of children with autism) [33].
No benefit
Secretin — We do not recommend secretin for children with ASD. It does not improve core features of ASD [34].
Secretin is a gastrointestinal hormone. It inhibits intestinal motility and release of gastric acid and stimulates secretion of pancreatic fluid and bicarbonate. The use of secretin as a potential therapy for children with ASD is based upon the hypothesis that autism is related to gastrointestinal abnormalities [35]. However, there is little evidence to support this hypothesis [36]. A 2012 systematic review that included 16 randomized controlled trials involving >900 children found no evidence that secretin improves the core features of autism [34]. No serious side effects were reported. (See "Autism spectrum disorder in children and adolescents: Pharmacologic interventions", section on 'Gastrointestinal problems'.)
Facilitated communication — We do not recommend facilitated communication as a means of communicating with children with ASD.
Facilitated communication is a technique in which a facilitator physically guides the hand of a nonverbal child in using an output device (eg, keyboard, mouse) for communication [37]. Reviews of published studies of facilitated communication found no evidence to support its use for individuals with communication impairment [32,38]. Controlled studies revealed that the facilitator, rather than the child, was providing information [39].
Facilitated communication must be distinguished from augmentative communication, an established method of nonverbal communication in which manual sign, picture exchange, switches, or voice output devices are used without the aid of a facilitator. Augmentative communication is an appropriate intervention in some children with ASD and is discussed separately. (See "Autism spectrum disorder in children and adolescents: Behavioral and educational interventions", section on 'Communication interventions'.)
Possible benefit, potential risk
Gluten-free casein-free diet — We do not suggest a gluten-free casein-free (GFCF) diet for children with ASD unless there is evidence of celiac disease or true gluten sensitivity. Evidence of efficacy is limited and weak [40]; strict adherence to the diet is difficult and may be associated with nutritional deficiencies (eg, calcium, vitamin D, amino acids) unless monitored by a registered dietician [41].
Despite the lack of evidence, many caregivers choose to follow a GFCF diet for their child with ASD. We counsel such caregivers about the need for adequate vitamin D, calcium, and protein intake. Rice milk, almond milk, and potato milk are not sufficient sources of protein. (See "Dietary recommendations for toddlers and preschool and school-age children".)
The use of the GFCF diet for children with ASD is based upon the hypothesis that increased gut permeability allows gluten and casein peptides to leak from the gut, causing excessive opioid activity and resulting in behaviors observed in ASD [12]. However, children with ASD have neither increased rates of celiac disease nor excessive amounts of opioid-like compounds in their urine [23,42-45].
Systematic reviews of randomized trials evaluating the GFCF diet in children with ASD have concluded that the evidence of benefit is limited and weak [40,41,46,47]. Limitations include lack of blinding, small sample size, and differences in patient population, interventions, and outcome measures.
In a meta-analysis of six randomized trials (143 participants), clinician-reported ASD core symptoms, caregiver-reported functional level, and behavioral difficulties were similar in children assigned to a GFCF diet or a regular diet [47]. The quality of the evidence is limited by inconsistency, imprecision, and risk of bias. In a subsequent randomized trial in 66 children (ages 36 to 69 months), no differences in autism symptoms, maladaptive behaviors, or intellectual abilities were detected after six weeks of the study diet [48].
Unknown benefit, potential risk — The therapies described in this section have little evidence of efficacy and are potentially harmful. Their use may compete with validated therapies for time, effort, and financial resources. Given the potential harms, we discourage their use in the treatment of ASD.
Intravenous immunoglobulin — We do not recommend intravenous immunoglobulin (IVIG) for the treatment of ASD in the absence of other indications for IVIG (eg, documented immune deficiency). (See "Immune globulin therapy in inborn errors of immunity", section on 'Indications'.)
The use of IVIG and other immune therapies for children with ASD is based on the hypothesis that ASD is related to dysregulation in the immune system [9,49]. The data underlying this hypothesis are limited [50,51]. Although small open-label trials of IVIG in children with ASD suggest improvement in some domains [52-54], the evidence is inconsistent [55,56], and adverse effects were common. In the only blinded, placebo-controlled randomized trial in 12 males with ASD, clinician ratings were similar in the IVIG and placebo groups, although there was greater improvement from baseline scores on some subscales of the Aberrant Behavior Checklist (ABC) or symptoms checklists [57]; the authors of the study noted that the benefits of IVIG may be limited to selected patients and cautioned against indiscriminate use.
IVIG is expensive. Potential adverse effects of IVIG and other immune therapies include transmission of bloodborne pathogens. (See "Intravenous immune globulin: Adverse effects", section on 'Infectious risks'.)
Chelation — We strongly discourage the use of chelation for the treatment of ASD. There is no evidence of efficacy and potential for serious harm.
Chelation is a process of administering a substance (such as ethylene diamine tetra-acetic acid [EDTA], 2,3-dimercaptosuccinic acid [DMSA], or 2,3-dimercaptopropane-1-sulfonate [DMPS]), to remove heavy metals from the body.
The use of chelation for ASD is based upon the hypothesis that the behaviors observed in children with ASD are secondary to toxicity from mercury or other heavy metals and that children with ASD do not excrete heavy metals effectively. However, there is little evidence to support this hypothesis [58]. The clinical manifestations of mercury toxicity do not resemble those of ASD, and evidence to support a causal relationship between thimerosal and autism is lacking. (See "Mercury toxicity", section on 'Clinical manifestations' and "Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor".)
The safety and efficacy of chelation therapy for ASD, including nonprescription oral or rectal products, has not been well studied in controlled trials [59,60]. The only randomized trial [61,62] had methodologic limitations [63]. Chelation agents bind ions nonspecifically and may result in decreased levels of calcium, iron, and magnesium as well as toxic heavy metals. When used for documented heavy metal poisoning, chelation requires close monitoring. Death due to hypocalcemia has been reported when sodium EDTA rather than calcium EDTA was used for chelation [64,65].
Hyperbaric oxygen — We do not recommend hyperbaric oxygen therapy (HBOT) as a treatment for ASD. It is costly and there is insufficient information about its efficacy.
The use of HBOT to treat autism is based upon the hypothesis that increasing atmospheric pressure enhances oxygen delivery to the brain to reduce swelling and promote brain recovery [66].
A 2016 systematic review [67] included only one randomized trial in 60 children, in which HBOT did not improve social interaction, behavioral problems, communication, or cognitive function in children with ASD. A subsequent review of the literature from 2015 to 2021 concluded that the effectiveness of HBOT for children with ASD is unconfirmed [68]. Adverse effects of HBOT include barotrauma to the middle ear, sinuses, or lungs; reversible myopia; pulmonary oxygen toxicity; and seizures. (See "Hyperbaric oxygen therapy", section on 'Complications'.)
Antimicrobial agents — We do not recommend antimicrobial agents (eg, antifungal agents [eg, nystatin, fluconazole], antibiotics, or antiviral agents) in the treatment of ASD. They have unproven efficacy and potential adverse effects.
The use of antimicrobial agents is based upon the hypothesis that individuals with ASD have an imbalance of intestinal microbes (eg, overgrowth of yeast or bacteria) [2,69].
Few controlled trials have evaluated antimicrobial therapies in children with ASD [2,70]. Adverse effects include hypersensitivity reaction, hepatotoxicity, anemia, diarrhea, exfoliative dermatitis, and promotion of antimicrobial resistance [23,37].
Vitamin B6 and magnesium — We do not recommend vitamin B6 (pyridoxine) and magnesium supplementation for the treatment of ASD.
Although there is a long history of treatment of mental health disorders with vitamin B6 and magnesium (which was added to reduce the side effects of vitamin B6), few high-quality studies have specifically evaluated B6-magnesium supplementation for ASD [9,71]. A 2010 systematic review of three small and methodologically flawed randomized trials (total of 33 patients) found the evidence inconclusive [72].
Megadoses of vitamin B6 (>100 mg/day) may result in neuropathy. (See "Overview of water-soluble vitamins", section on 'Vitamin B6 (pyridoxine)'.)
Other interventions — Other interventions with unproven benefit for ASD and potential adverse effects include [2]:
●Vitamin A; adverse effects of vitamin A are discussed separately. (See "Overview of vitamin A", section on 'Excess'.)
●Vitamin D supplementation outside of vitamin D deficiency, and in excess of daily requirements and tolerable upper intake level (table 3); in a small randomized trial, vitamin D supplementation did not improve the core symptoms of ASD [30]. Adverse effects of excess vitamin D are discussed separately. (See "Overview of vitamin D", section on 'Excess'.)
●Homeopathic remedies (may contain unlabeled toxic ingredients [73]).
●Vagus nerve stimulation is an accepted intervention for the management of epilepsy; its effectiveness for ASD is unproven. Adverse effects of vagus nerve stimulation therapy are discussed separately. (See "Vagus nerve stimulation therapy for the treatment of epilepsy", section on 'Side effects and complications'.)
●Stem cell transplantation is being investigated as a treatment for some central nervous system disorders requiring neural regeneration (eg, spinal cord injury) [74]. However, given that ASD is a neurodevelopmental disorder of neural connectivity, regenerative treatment with stem cells does not make sense physiologically [75]. It is potentially harmful [76,77], as well as expensive.
Given the lack of proven benefit and potential harms, we do not recommend these therapies for our patients with ASD.
Possible benefit, low risk — The therapies described in this section have possible benefit and low risk. Given the unestablished benefits, with the exception of melatonin for sleep disturbance, we do not actively encourage their use for the management of ASD. However, we do not discourage caregivers from using them if they choose to do so. In that case, we monitor for side effects, interactions, and effects on prescribed/recommended therapy.
Music therapy — Music therapy may be beneficial for children with ASD and is unlikely to be harmful [2,78-80]. Pending additional studies, we do not actively encourage using music therapy to manage core features of ASD unless it is a component of a broader comprehensive behavior program. (See "Autism spectrum disorder in children and adolescents: Overview of management", section on 'Behavioral and educational interventions'.)
The use of music therapy for children with ASD is based upon the hypothesis that engaging in musical interaction (sometimes understood to be a kind of nonverbal or preverbal language) may facilitate the development of communication skills and capacity for social interaction [80].
A systematic review of 26 clinical trials (1165 participants) that compared music therapy with standard care or "placebo" therapy (similar treatment without music) concluded with moderate certainty that immediately after the intervention, music therapy probably results in global improvement, likely improves total autism severity and quality of life, and probably does not increase adverse events [80]. Whether music therapy improves social interaction, nonverbal communication, and verbal communication remains uncertain. Although differences between groups were not detected, the certainty of the evidence was low (due to risk of bias and imprecision).
Melatonin — The use of melatonin for sleep disturbance in children with ASD is discussed separately. (See "Autism spectrum disorder in children and adolescents: Pharmacologic interventions", section on 'Sleep disturbance'.)
Oxytocin — The use of oxytocin in children with ASD is discussed separately. (See "Autism spectrum disorder in children and adolescents: Pharmacologic interventions", section on 'Investigative therapies for social deficits'.)
Therapeutic horseback riding — We do not actively encourage therapeutic horseback riding (hippotherapy) as a core treatment for children with ASD, but it is not discouraged if monitored appropriately in the context of a broader comprehensive behavioral/educational program. Although there is some evidence of benefit [81-85], additional studies are necessary before it can be actively recommended [2].
Therapeutic horseback riding is hypothesized to stimulate multiple domains of functioning (eg, cognitive, social, gross motor) in children with ASD [81]. In a randomized trial that compared 10 weeks of therapeutic horseback riding with 10 weeks of a barn activity not involving horses in 116 children and adolescents with ASD, therapeutic horseback riding improved measures of irritability and hyperactivity after approximately five weeks [82]. Therapeutic horseback riding also improved social cognition and social communication as assessed by parent report. In a smaller nonrandomized study, 19 children with autism who participated in 12 weeks of therapeutic horseback riding demonstrated improvements in attention, distractibility, and social motivation compared with 15 waitlist controls [81].
Therapeutic horseback riding is associated with a risk of injury similar to that in other "limited contact" recreational activities (eg, baseball, skating). When discussing horseback riding with caregivers who choose to participate, it is important to emphasize the need to wear a helmet and for appropriate supervision [2].
Other types of animal/pet therapy — Observational studies suggest that the presence of animals may reduce social stress and increase social behaviors in patients with ASD [86,87], but additional studies are necessary before animal therapy can be recommended [88].
A pilot randomized trial that compared canine-assisted occupational therapy with standard occupational therapy (waitlist control) in 22 children with ASD found a trend toward improved on-task behavior and goal attainment with canine-assisted occupational therapy, but additional study is necessary [89].
Sulforaphane — We do not encourage sulforaphane supplementation for children with ASD. Additional studies documenting benefit are necessary.
Sulforaphane is an antioxidant derived from broccoli sprout extracts that increases the activity of genes that protect aerobic cells against oxidative stress, inflammation, and deoxyribonucleic acid (DNA) damage [90,91]. It is hypothesized to reverse abnormalities associated with ASD including neuroinflammation; oxidative stress; and decreased glutathione synthesis, mitochondrial function, and oxidative phosphorylation.
The effects of sulforaphane on ASD were evaluated in a trial in which young men (age 13 to 27 years) were randomly assigned to receive 18 weeks of daily sulforaphane (n = 29) or placebo (n = 15) [92]. During treatment, sulforaphane recipients had improved behavior compared with baseline as assessed by parents and clinicians on the ABC, Social Responsiveness Scale, and Clinical Global Impression Improvement Scale. When sulforaphane was discontinued, behavior returned to baseline. In a subsequent placebo-controlled, randomized trial in 57 children (age 3 to 12 years) with ASD, 45 were available for follow-up after 15 weeks (22 in the sulforaphane group and 23 in the placebo group) [93]. Clinical effects varied with outcome measure (no benefit detected on the Ohio Autism Clinical Impressions Scale or the Social Responsiveness Scale, Second Edition; improvement on the ABC) and were less notable than the trial in young men [93]. Sulforaphane appeared to be well-tolerated in both trials, but the trials were too small to adequately assess adverse effects. Although these results are promising, additional information is needed.
Pending additional study, we do not specifically recommend that children with ASD eat broccoli sprouts or other sulforaphane-rich foods (eg, brussel sprouts, broccoli), but eating these vegetables is not discouraged given the other health benefits of these foods. Study participants received 50 to 150 micromol of sulforaphane, much more than can be obtained from food [94].
Transcranial magnetic stimulation — We do not recommend transcranial magnetic stimulation (TMS) for children with ASD, except as part of a clinical trial. Although it appears to be safe in the context of clinical trials, additional study is necessary before TMS can be recommended for treatment of ASD in children [2,95].
TMS is an energy-based therapy that is proposed to work through electromagnetic induction, which modifies neuroexcitability. Controlled and uncontrolled studies have demonstrated potential benefit in patients with depression, bipolar illness, schizophrenia, epilepsy, and Tourette syndrome. (See "Evaluation and management of drug-resistant epilepsy", section on 'Other stimulation approaches' and "Unipolar depression in adults: Indications, efficacy, and safety of transcranial magnetic stimulation (TMS)".)
The use of TMS for children with ASD is based upon the hypothesis that autism is related to a disturbance of cortical modularity [96]. A 2016 literature review found some evidence that TMS may reduce symptoms of ASD (core symptoms and associated symptoms), but more rigorous study is necessary [95]. TMS is generally considered safe in children and adults [97,98]. Seizures, the most serious TMS adverse event, are extremely rare [99].
Other interventions — Other interventions that lack definitive scientific evidence of a benefit but are unlikely to be harmful for children with ASD include [2,78,100]:
●Yoga [101-103].
●Body work and energy therapies (eg, qigong massage, therapeutic touch, healing touch, Reiki) [79,103-106].
●Biofeedback/neurofeedback [107,108] – In biofeedback/neurofeedback, behavioral therapy is focused on achieving self-regulation of cortical electrical activity as measured by electroencephalogram, often using visual feedback. Reported side effects are minimal but can include headache. Although neurofeedback is safe, it may be expensive [10], and benefits remain unproven for the core symptoms of ASD.
●Hypnotherapy.
●Vitamin C (doses up to 2 g/day [10]).
●Folinic acid [111,112] and folic acid [113].
Given the lack of definitive evidence of benefit, we do not encourage these interventions for our patients with ASD.
Unknown benefit, low risk — The therapies described in this section have unknown benefit but low risk. Given the unknown benefits, we do not encourage them for the management of ASD. If caregivers choose to use them, we monitor for side effects, interactions, and effects on prescribed/recommended therapy.
Auditory integration training — We do not encourage using auditory integration training (AIT) for children with ASD. Although the risk of adverse effects is low, the efficacy is unproven and it is expensive [2,79].
The use of AIT in children with ASD is based upon the hypothesis that repeated exposure to altered sound via headphones functionally modifies central auditory processing, impacting language and behavior.
Systematic reviews of randomized trials have concluded that auditory integration therapy does not improve language outcomes in children with ASD [33,79,114]. The evidence is limited by inconsistency and small sample size.
Omega-3 fatty acids — Although there might be some benefits, we do not advise use of omega-3 fatty acids as a therapy for the core symptoms of ASD. Omega-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) are essential fatty acids with potential cardiovascular benefits. Some studies suggest that plasma omega-3 concentrations in children with ASD are decreased, but no clear clinical correlation has been established [115-117].
Systematic reviews of randomized trials evaluating omega-3 fatty acids for ASD have had inconsistent findings [40,118-121]. Most have concluded that omega-3 fatty acid supplementation does not improve core symptoms of ASD or symptoms associated with ASD, but is not likely to be harmful [40,118-120]. Although a meta-analysis concluded that omega-3 supplementation had small beneficial effects on language, social deficits, and associated symptoms (eg, inattention, irritability, behavioral difficulties, cognition) [121], the findings are limited by the quality of the included studies [122].
The American Heart Association suggests two servings of fish per week for the cardiovascular benefit. (See "Dietary recommendations for toddlers and preschool and school-age children", section on 'Meat and protein'.)
Common side effects of omega-3 supplementation include gastrointestinal distress (eg, nausea, diarrhea). No major side effects were reported in the studies of omega-3 supplementation for ASD [118,119,123,124]. Omega-3 fatty acid supplementation should be used with caution in patients with bleeding disorders or sensitivity to fish.
No specific dosing guidelines for omega-3 fatty acids are available. Studies in children with ASD used 1.3 and 1.5 g/day [123,124].
Omega-3 fatty acid supplementation for children with developmental coordination disorder and attention deficit hyperactivity disorder is discussed separately. (See "Developmental coordination disorder: Management and outcome", section on 'Fatty acid supplementation' and "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis", section on 'Essential fatty acid supplementation'.)
Probiotics — Probiotics are hypothesized to address an imbalance of intestinal microbes in individuals with ASD. US Food and Drug Administration regulation of probiotics depends upon how they are categorized (eg, biologic product, drug, dietary supplement, medical food, food ingredient [125]). Those that are less stringently regulated may contain unlabeled ingredients or species [126].
Although there continues to be great interest and ongoing research into the relationship between the gut microbiome and ASD, there is not enough evidence to determine if there is a causal relationship and, if so, to understand the direction of this relationship (eg, there is suggestion that the restricted diet of many individuals with ASD impacts the gut microbiome [127] rather than the microbiome causing the symptoms of ASD).
We do not encourage probiotics for the management of ASD. Although they are unlikely to be harmful, they have not been rigorously studied in children with ASD. A systematic review that included six clinical trials concluded that probiotics have limited efficacy in the management of gastrointestinal or behavioral symptoms in children with ASD [128]. The included studies used different strains, concentrations, and duration of probiotics. There is some evidence to suggest that probiotics may be beneficial for other conditions (eg, acute gastroenteritis, functional abdominal pain). (See "Acute viral gastroenteritis in children in resource-abundant countries: Management and prevention", section on 'Probiotics and prebiotics' and "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Management of symptoms'.)
Cannabinoids — We do not encourage medical marijuana or cannabinoids for the treatment of ASD or related symptoms. Cannabinoids include cannabidiol (CBD, the nonpsychoactive component of marijuana), tetrahydrocannabinol (THC, the psychoactive component), and dronabinol (synthetic THC), among others. Although CBD is available for the treatment of certain types of epilepsy in children and appears to be safe, the benefits for children with ASD are uncertain [129,130]. (See "Lennox-Gastaut syndrome" and "Dravet syndrome: Management and prognosis", section on 'Cannabidiol'.)
Although an animal model suggests that endocannabinoid signaling pathways may play a role in genetic disorders related to ASD (eg, fragile X syndrome) [131], research evaluating the direct effects of medical cannabis in individuals with ASD is limited. In a randomized trial in 150 participants (age 5 to 21 years) with ASD, efficacy of benefit was inconsistent [132]. The study was limited by a lack of pharmacokinetic data and a wide range of subject ages and functional levels. Additional randomized and open trials of the effects of cannabinoids on the behavior of children with ASD are underway [133-135]. Observational studies report subjective improvements in behavioral problems (self-injury, hyperactivity), anxiety, and sleep, along with reduced need for other psychoactive medications [136-140]. Limitations include lack of objective assessment tools, poor follow-up, attrition, and lack of uniform cannabinoid dosing.
In randomized trials and observational studies of cannabinoids in patients with ASD, adverse effects included somnolence, decreased appetite, irritability, and restlessness [132,136-140]. In randomized trials of CBD in children with Lennox-Gastaut syndrome and Dravet syndrome, adverse effects included somnolence, fever, decreased appetite, diarrhea, and vomiting [141-143]. However, some children discontinued CBD because of elevation of liver aminotransferase concentrations. (See "Lennox-Gastaut syndrome" and "Dravet syndrome: Management and prognosis", section on 'Cannabidiol'.)
Additional information about the medical use of marijuana is provided separately. (See "Cannabis use and disorder: Epidemiology, pharmacology, comorbidities, and adverse effects", section on 'Medico-legal context'.)
Other interventions — Other interventions with unknown benefit but low risk of harm include [2]:
●Methylcobalamin and N-acetylcysteine [14,144-146].
●Zinc.
●Herbal products.
●Amino acids, which include dimethylglycine (DMG, a derivative of glycine) as well as others (eg, taurine, lysine, gamma-aminobutyric acid [GABA]) [147,148].
●Digestive enzymes [40,149,150].
●Mindfulness therapy has been studied in parents of children with ASD and in children with ASD [151-156], but the quality of the evidence is low due to methodologic limitations (eg, small sample size, self-reported outcome measures, ) [103,157]; mindfulness therapy is unlikely to be harmful.
●Acupuncture – Although generally considered to be safe [158-160], there is a risk of injury in uncooperative patients.
●Craniosacral manipulation – Although systematic reviews suggest that craniosacral manipulation is low risk [2], adverse effects may be underreported [161].
●Chiropractic (generally safe for children without spinal abnormalities).
RESOURCES — For pediatric health care providers seeking more information about complementary and alternative (CAM) therapies or current trials of CAM therapies in children with ASD, the following websites might be useful [162]:
●ClinicalTrials.gov – The clinical trials registry of federally and privately supported clinical trials
●The National Center for Complementary and Integrative Health
●Association for Science in Autism Treatment
●The Autism Society of America
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Autism spectrum disorder".)
SUMMARY AND RECOMMENDATIONS
●Autism spectrum disorder (ASD) is a neurodevelopmental disorder with an incompletely understood etiology and no known cure. Many caregivers of children with ASD seek both conventional and complementary and alternative (CAM) therapies as part of the process of understanding and accepting the diagnosis.
●It is important to ask caregivers of children with ASD specifically about the use of CAM therapies and to work with them in a sensitive manner (table 2). (See 'General principles' above.)
●Medical practitioners play an essential role in helping caregivers evaluate information regarding CAM for children with ASD. It is important for clinicians to become knowledgeable about CAM therapies and to provide balanced information and advice about the potential benefits and risks. (See 'Counseling caregivers' above.)
●Few CAM therapies have been proven effective/ineffective or safe/unsafe in controlled trials (table 1). Given the uncertainty, the clinician and family must weigh the unknown benefit against the potential risks, which include competition with validated treatment for time, effort, and financial resources. (See 'Classification according to benefits and risks' above.)
●Secretin and facilitated communication are ineffective. We recommend not using secretin or facilitated communication for children with ASD (Grade 1A). (See 'Secretin' above and 'Facilitated communication' above.)
●We suggest not using a gluten-free casein-free diet for children with ASD who do not have celiac disease or gluten sensitivity (Grade 2C). Adherence to the diet is difficult and may be associated with nutritional deficiencies. (See 'Gluten-free casein-free diet' above.)
●We strongly discourage CAM therapies with unknown benefits and potential risks in the treatment of ASD. These therapies include intravenous immunoglobulin, chelation, hyperbaric oxygen, antimicrobial agents, vitamin B6 and magnesium, vitamin A, homeopathy, vagus nerve stimulation, and stem cell transplantation (table 1). (See 'Unknown benefit, potential risk' above.)
●We do not actively encourage CAM therapies with possible/unknown benefit and low risk (table 1) for our patients with ASD. Such therapies compete with validated therapies for time, effort, and financial resources. However, if families choose to use them, we monitor for side effects, interactions, and effects on prescribed/recommended therapies. (See 'Possible benefit, low risk' above and 'Unknown benefit, low risk' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Carolyn Bridgemohan, MD (deceased), who contributed to an earlier version of this topic review.
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