By Ellen Feldman, MD
Altru Health System, Grand Forks, ND
Dr. Feldman reports no financial relationships relevant to this field of study.
SUMMARY POINT
- These authors reviewed some of the more common treatments for autism spectrum disorder and place each into one of four categories to guide the medical practitioner when faced with choosing an intervention for a person with autism spectrum disorder.
SYNOPSIS: Selected treatments for autism spectrum disorder are reviewed and placed into one of four categories (ranging from recommend to avoid) with a goal of creating a practical blueprint for the medical practitioner.
SOURCE: Klein N. Kemper KJ. Integrative approaches to caring for children with autism. Curr Probl Pediatr Adolesc Health Care 2016;46:195-201.
“We know what we are, but know not what we may be.”
Shakespeare, Hamlet
Autism spectrum disorder (ASD) is aptly named. Symptoms emerge in very early childhood with varying degrees of severity. Shared core diagnostic criteria include functional impairment due to social communication deficits, inflexibility, and unusual levels of reactivity to sensory input sometimes leading to agitation or outbursts. Intelligence levels range from intellectual impairment to extremely gifted. Despite shared characteristics, this disorder truly exists on a spectrum from mild impairment with need for little intervention to severe impairment with need for lifetime support. The diversity of clinical presentation is mimicked by diversity of intervention — treatment is targeted toward reduction of symptoms, as there is no “cure” or identified single causative agent of ASD.1
The CDC estimates that one in 68 children in the United States are diagnosed with ASD. These numbers hold true across racial and socioeconomic groups, but differ according to gender, as ASD is about 4.5 times more common in boys than in girls.2 With limited medical interventions available and with concern about timely intervention in young children, up to 85% of families affected by this disorder pursue complementary or alternative remedies.3,4
Noting this trend, Klein and Kemper reviewed some of the more common treatments for ASD and place each into one of four categories: recommend, monitor, tolerate, or avoid. These groupings are meant to guide the medical practitioner when faced with choosing an intervention for a person with ASD. The authors remind those treating children with ASD that each child is an individual and that even the recommended treatments may not work for every person with ASD. Treatment and interventions need to be re-evaluated and reassessed over time, with consideration of the effect of environmental changes (for example, if a child is entering a new school or classroom) and stages of development at each visit.
COMMENTARY
This section lists the categories created by Klein and Kemper, as well as the interventions they placed within each category. I have provided some background and thoughts regarding clinical application of each intervention.
Recommend: Robust Evidence of Efficacy and Safety
To be placed in this category, Klein and Kemper stipulated that safety and effectiveness must be supported by at least two randomized, clinical trials (RCT) with adequate number of subjects or a systematic review.
1. Healthy lifestyle: Address exercise, nutrition, sleep, and social interaction, and avoid neurotoxins. This can be challenging in children with ASD who often demonstrate a “limited food repertoire,” leading to risk of nutritional deficiencies. Parental education and instruction regarding behavioral techniques can be useful to help achieve nutritional balance. Behavioral interventions noted below can be used to encourage a wider variety of foods or supplements can be used.5
Prenatal vitamin supplements may help with prevention (see vitamin section.)
2. Applied behavior analysis (ABA) and parent implemented training (PIT): ABA is a type of behavioral intervention often conducted in an intensive manner with young children. ABA-trained therapists identify target behaviors and then design specific interventions aimed at improving social skills and teaching cooperative play, self-care, and communication using reinforcement and other behavioral techniques. There is evidence that applications of ABA as early as toddler stage of development are useful in ASD. PIT is an extension of ABA using parent assistance to extend and reinforce concepts. Each of these may be covered by insurance.6,7
A 2012 Cochrane review examined evidence for early intensive behavioral intervention (therapies based on ABA) for treatment of ASD in young children. The conclusion was that while there is some evidence of effectiveness, more well-designed studies are needed.8
3. Melatonin: More than 50% of children with ASD have sleep problems. Melatonin (1-3 mg oral) can be used to address sleep when these problems interfere with daytime functioning. Sleep hygiene should be addressed with or without use of melatonin.9
4. Music therapy: An updated 2014 Cochrane review concluded that music therapy delivered by a trained music therapist (individually or in small groups) has clear benefit in ASD at least in the short- to medium-term. Advancement of social skills as well as communication in children with ASD are noted.10
5. Neurofeedback: This is a type of biofeedback that uses EEG information to help children with ASD learn to self-regulate. Electrodes are placed on a child’s scalp; brainwaves are represented in a concrete manner (such as a floating ball or color) designed to allow a child to affect change. Subsequent steps link the feedback to behavior. Although there are a few promising studies, cost limits the use of this intervention, which insurance rarely covers.11
Monitor
The few interventions in this category have evidence for efficacy coexisting with concerns about safety, toxicity, or cost.
1. Risperidone (Risperdal) and aripiprazole (Abilify): These medications are FDA-approved to treat children older than 6 years of age for severe aggression and agitation in ASD. Dosages range according to severity of symptoms, but a good general principal is “start low and go slow.” Side effects include metabolic syndrome, weight gain, development of diabetes, tardive dyskinesia, and sedation. Baseline lipid profile, fasting glucose monitoring, and frequent reassessment (monthly in some cases) for efficacy and development of side effects is recommended.12
2. Restrictive diets: Gluten-free/casein-free has benefits in treatment of comorbid gastrointestinal difficulties. Side effects noted by the authors include poor nutrition if the diet is not well structured; authors advise use of a registered dietician to assist with this intervention.13
Tolerate
Limited medical evidence supporting efficacy; overall are safe and/or low cost; use while research continues.
1. Dietary supplements
Omega-3 fatty acids: Studies show mixed results in reducing irritability and aggression associated with ASD and more consistently positive results in improvement of mood. Doses typically used are 1.5 grams/day (0.84 g/d eicosapentaenoic acid, 0.7 g/d docosahexaenoic acid.) The authors noted that more studies with more subjects may allow omega-3s to be moved to recommended category.14
Vitamins B6, folate, B12: There have been several reports of above-average serum levels of homocysteine in some children with ASD. Vitamins B6, folate, and B12 act as co-factors to the enzymes needed in homocysteine metabolism. Studies are underway to see if supplementation reduces homocysteine levels in children with ASD and if there are associated changes in behavior.15
Use of folic acid in pregnant mothers is associated with a reduced risk of ASD in offspring; studies look favorable for supplementing alpha omega-3, iron, and iodine in pregnancy.16
Vitamin C: High-dose (110 mg/kg) ascorbic acid supplementation is supported in preliminary studies to reduce irritability in children with ASD.17
Vitamin D: Insufficiency and deficiency are commonly found in children with ASD; preliminary studies are favorable regarding correlating supplementation with symptom improvement.18
Combined vitamin/mineral supplement: An RCT involving patients with ASD showed statistically significant improvement in both metabolic status and several measures of ASD symptoms following a three-month period. This is perhaps the most rigorous and convincing study thus far linking ASD symptom reduction to nutritional health.19
2. Occupational therapy (including sensory integration): Occupational therapists develop and improve practical skills via play-assisted therapy, cognitive-behavioral therapies, or parent-supported therapies. Sensory integration includes techniques such as brushing, swinging, and pressure and may be used within a school setting. Small studies have produced mostly favorable results; implementation can be difficult without available resources (such as trained therapists).20
3. Animal-assisted therapy: The authors noted that some small studies support equine-assisted activities and therapies. There is speculation that the effect is derived from physical impact (pressure sensation similar to massage) and/or from an emotional impact involving non-verbal communication.21
4. Yoga: Two recent studies examined teaching yoga techniques to children with ASD to aid in management of disruptive behavior. One 2012 study looked at a manualized form of yoga designed for classroom use and the other study looked at a combination of yoga, dance, and music therapy. Although results are impressive, the study designs do not allow clear conclusions regarding the specific efficacy of the yoga intervention.22,23
5. Massage: A 2011 review study looked at 132 published studies regarding any type of massage in ASD. Only six of these studies met criteria for inclusion in the review. Results of these six studies linked massage with improvement in several measures of ASD, but none of the trials were sufficiently non-biased to allow firm conclusions.24
6. Chiropractic manipulation: A 2011 review article concluded there is simply not enough research to form a conclusion regarding the effectiveness of chiropractic manipulation in the care of ASD. There are a few case studies that point to favorable results, and the authors’ note this intervention is generally supported by insurance.25
7. Acupuncture: Two review articles (2011, 2012) looked at acupuncture in ASD treatment. Both found multiple studies reporting improvement in measures of ASD with acupuncture; however, the variability of the studies, including acupoints used and treatment duration, limit conclusions and point to the need for more rigorous studies.26,27
8. Transcranial magnetic stimulation (TMS): Strong, rapidly alternating magnetic currents stimulate specified areas of the brain. There are about eight small trials of TMS in ASD (more commonly TMS is used in treatment-refractory depression); it remains considered an experimental treatment in ASD.28
Avoid
These lack evidence of efficacy and have high cost and/or risk.
1. Hyperbaric oxygen: Studies show no evidence of consistent improvement in symptoms of ASD and treatment is quite expensive.29
2. Chelation: Chelation has been proposed as a way to excrete heavy metals that may worsen symptoms of ASD. According to a 2015 Cochrane review, “no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD.” The same reports noted the risk of adverse effects from this procedure are significant and include renal and hepatic toxicity.28 There are no studies confirming that heavy metal burden worsens ASD symptoms.
3. Secretin: A hormone released in the gastrointestinal tract, secretin has been studied in the treatment of ASD after several promising case studies were reported in the late 1990s. A comprehensive 2011 review article found seven RCTs, none of which supported effectiveness of secretin in the treatment of ASD.31
CONCLUSION
Treating a child with ASD is complex. The wide variability in type and severity of presenting symptoms, the potential disabling features of the symptoms, and the limited research regarding efficacy and safety of various interventions make treatment difficult. Often a decision to treat symptoms becomes a judgment call weighing the relative effect of functional impairment against the risk associated with intervention. Yet, a successful intervention can be extraordinarily effective in helping a child operate, grow, and learn within a school and family setting. Recognizing the stakes, many families turn to integrative techniques to maximize the potential and aid their affected child navigate a complex world. Knowing and understanding the research is invaluable when assisting families in their quest to make an informed decision regarding intervention.
REFERENCES
- National Institute of Mental Health. Autism Spectrum Disorder. Available at: http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-asd/index.shtml. Accessed June 1, 2016.
- CDC. Autism Spectrum Disorder (ASD). Available at: http://www.cdc.gov/ncbddd/autism/facts.html. Accessed June 1, 2016.
- Levy S, Hyman S. Complementary and alternative medicine treatments for children with autism spectrum disorders. Child Adolesc Psychiatr Clin N Am 2008;17:803-820, ix.
- Owen-Smith AA, Bent S, Lynch FL, et al. Prevalence and predictors of complementary and alternative medicine use in a large insured sample of children with autism spectrum disorders. Res Autism Spectr Disord 2015;17:40-51.
- Curtin C, Hubbard K, Anderson SE, et al. Food selectivity, mealtime behavior problems, spousal stress, and family food choices in children with and without autism spectrum disorder. J Autism Dev Disord 2015;45:3308-3315.
- Bradshaw J, Steiner AM, Gengoux G, et al. Feasibility and effectiveness of very early intervention for infants at risk for autism spectrum disorder: A systematic review. J Autism Dev Disord 2015;45:778-794.
- Autism Speaks. Applied Behavior Analysis (ABA). Available at: https://www.autismspeaks.org/what-autism/treatment/applied-behavior-analysis-aba. Accessed June 1, 2016.
- Reichow B, Barton EE, Boyd BA, et al. Early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASD). Cochrane Database Syst Rev 2012;10:CD009260.
- Malow B, Adkins KW, McGrew SG, et al. Melatonin for sleep in children with autism: A controlled trial examining dose, tolerability, and outcomes. J Autism Dev Disord 2012;42:1729-1737.
- Geretsegger M, Elefant C, Mossler KA, et al. Music therapy for people with autism spectrum disorder. Cochrane Database Syst Rev 2014;6:CD004381.
- Hurt E, Arnold LE, Lofthouse N. Quantitative EEG neurofeedback for the treatment of pediatric attention-deficit/hyperactivity disorder, autism spectrum disorders, learning disorders, and epilepsy. Child Adolesc Psychiatr Clin N Am 2014;23:465-486.
- American Academy of Child and Adolescent Psychiatry. Practice Parameter for the use of atypical antipsychotic medications in children and adolescents. Available at: https://www.aacap.org/App_Themes/AACAP/docs/practice_parameters/Atypical_Antipsychotic_Medications_Web.pdf. Accessed June 1, 2016.
- Mari-Bauset S, Zazpe I, Mari-Sanchis A, et al. Evidence of the gluten-free and casein-free diet in autism spectrum disorders: A systematic review. J Child Neurol 2014;29:1718-1727.
- Mehl-Madrona L, Leung B, Kennedy C, et al. Micronutrients versus standard medication management in autism: A naturalistic case-control study. J Child Adolesc Psychopharmacol 2010;20:95-103.
- Kaluzna-Czaplinska J, Zurawicz E, Michalska M, et al. A focus on homocysteine in autism. Acta Biochim Pol 2013;60:137-142.
- Suren P, Roth C, Bresnahan M, et al. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA 2013;309:570-577.
- Dolske MC, Spollen J, McKay S, et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry 1993;17:765-774.
- Saad K, Abdel-Rahman AA, Elserogy YM, et al. Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children. Nutr Neurosci 2015; April 15 [Epub ahead of print].
- Adams J, Audhya T, McDonough-Means S, et al. Effect of a vitamin/mineral supplement on children and adults with autism. BMC Pediatr 2011;11:111.
- Case-Smith J, Arbesman M. Evidence-based review of interventions for autism used in or of relevance to occupational therapy. Am J Occup Ther 2008;62:416-429.
- Gabriels RL, Pan Z, Dechant B, et al. Randomized controlled trial of therapeutic horseback riding in children and adolescents with autism spectrum disorder. J Am Acad Child Adolesc Psychiatry 2015;54:541-549.
- Koenig KP, Buckley-Reen A, Garg S. Efficacy of the Get Ready to Learn yoga program among children with autism spectrum disorders: A pretest–posttest control group design. Am J Occup Ther 2012;66:538-546.
- Rosenblatt LE, Gorantla S, Torres JA, et al. Relaxation response-based yoga improves functioning in young children with autism: A pilot study. J Altern Complement Med 2011;17:1029-1035.
- Lee MS, Kim JI, Ernst E. Massage therapy for children with autism spectrum disorders: A systematic review. J Clin Psychiatry 2011;72:406-411.
- Alcantara J, Alcantara JD, Alcantara J. A systematic review of the literature on the chiropractic care of patients with autism spectrum disorder. Explore (NY) 2011;7:384-390.
- Ming X, Chen X, Wang XT, et al. Acupuncture for treatment of autism spectrum disorders. Evid Based Complement Altern Med 2012;2012:679845.
- Lee MS, Choi TY, Shin BC, et al. Acupuncture for children with autism spectrum disorders: A systematic review of randomized clinical trials. J Autism Dev Disord 2012;42:1671-1683.
- Oberman LM, Rotenberg A, Pascual-Leone A. Use of transcranial magnetic stimulation in autism spectrum disorders. J Autism Dev Disord 2015;45:524-536.
- Ghanizadeh A. Hyperbaric oxygen therapy for treatment of children with autism: A systematic review of randomized trials. Med Gas Res 2012;2:13.
- Cochrane. Chelation for autism spectrum disorder (ASD). Available at: http://www.cochrane.org/CD010766/BEHAV_chelation-for-autism-spectrum-disorder-asd. Accessed June 1, 2016.
- McPheeters ML, Warren Z, Sathe N, et al. A systematic review of secretin for children with autism spectrum disorders. Pediatrics 2011;127:e1312-1321.
Selected treatments for autism spectrum disorder are reviewed and placed into one of four categories (ranging from recommend to avoid) with a goal of creating a practical blueprint for the medical practitioner.
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