Complementary and Alternative Treatments For Autism Spectrum Disorder

Arline Kaplan © 2013 (All Rights Reserved)

More than half of parents of children with autism spectrum disorders (ASD) give them complementary or alternative treatments (CATs).  Aware that many parents are acting with little or no guidance, experts recently reviewed the scientific evidence for 19 CATs, recommending three and listing several others as worthy of a monitored trial.1

Parents may choose CATs, because they are concerned about the safety and side effects of prescribed medications, according to one study. 2 Another reason can be their desperation.

“Often, parents come in and want to consider anything that might help their child,” said Robert Hendren, DO, Professor and Vice Chair of the Department of Psychiatry at the University of California, San Francisco (UCSF), and one of the review’s coauthors. “Doctors should really take them seriously rather than being dismissive and telling them not to consider CATs.”

Physicians need to be knowledgeable about CATs, he explained, and be willing to work with families in finding scientific and reliable information and in deciding how much risk they want to take and how much money they want to spend.

Nicholas Lofthouse, PhD., lead author of the review and Assistant Clinical Professor in the Department of Psychiatry at Ohio State University warned that  “most CATs for ASD should be considered potential or ‘wanna-be’ CATs.”
” Even though such approaches as folic acid, chelation, probiotics and animal-assisted therapy are called complementary and alternative treatments for the sake of clarity, “ he said, “without rigorous scientific research, we don’t actually know whether these so-called ‘treatments’ really are effective for treating autistic symptoms.”

In their article, Lofthouse and colleagues reviewed 13 orally administered (ingestible) and 6 externally administered (noningestible) CATs for ASD. For each one, they described its definition, rationale for use/mechanism, current research support (e.g., open-label trials or randomized controlled trials), safety issues, limitations and future directions.  They also applied a clinical guideline, evaluating treatments based upon whether they are sensible, easy, cheap and  safe (SECS).
The review authors recommended three CATs: melatonin, RDA/RDI multivitamin/mineral and massage therapy.

“There is some good scientific evidence for them, and they also seem sensible, easy, relatively cheap and safe,” said Lofthouse.

The authors also suggested several CATS worth considering for short, monitored trials, if conventional treatments for ASD and the recommended CATs have been given a reliable trial and been found ineffective or if patients and parents refused conventional treatments.

The CATs considered “acceptable” for a trial were B6 and magnesium, folic acid, omega-3, L-Carnosine, probiotics, and GI medication (when GI problems are present), iron supplementation (upon confirmed iron deficiency) and chelation (upon confirmed heavy metal toxicity from reliable testing).  Acceptable externally administered CATs included acupuncture, exercise, music therapy and animal-assisted therapy.

Some CATs reviewed were not recommended, because “they failed to show  positive effects across several randomized control trials.”  These included auditory integration therapy, facilitated communication, gluten/casein-free diets, hyperbaric oxygen therapy and secretin.  Because of ethical/safety issues, the authors did not recommend faradic skin shock (electro-aversive therapy) or packing therapy (wrapping a child tightly in cold, wet sheets—with only their head left free—followed by psychiatrically trained staff talking to them about their feelings).

The review authors also mentioned some 55 CATs, including deep pressure therapy, ketogenic diet and St. John’s Wort, with insufficient evidence to evaluate.

Asked why he and others embarked on a review of CATs, Lofthouse cited safety, efficacy, time, money, energy, hope and research impetus.

“We sometimes give these CATs to kids who are nonverbal and unable to communicate that an intervention is having a positive or negative effect.  So we really need to make sure they are safe,” he said.  “We also need to ensure they are working above and beyond the placebo effect.”

The third reason, he said, is because patients, parents and health care providers invest a lot of time, energy, money and hope in the treatments. The fourth reason, he said, is the study of possible treatments can provide “more information about potential causes of ASD and autism, as well as the mechanism affecting its developmental trajectories. “

Step-by-step

When considering CATs for ASD, Lofthouse said he and colleagues support a step-by-step process.

“We never recommend that any patients go straight to complementary and alternative treatments, although patients and families may want to do so,” Lofthouse said.  “Instead, we counsel them to consider the conventional treatments first, such as medications and  ABA [Applied Behavioral Analysis].”

While no medications are currently established to treat ASD core symptoms, the Food and Drug Administration (FDA) has approved risperidone (Risperdal) and aripiprazole (Abilify) for treatment of irritability in 5 to 16 years olds with ASD.  Off-label medications are often prescribed for co-occurring behaviors, such as anxiety, agitation and impulsivity/hyperactivity.

Before initiating  monitored trials of orally administered CATs, Lofthouse and colleagues recommend that clinicians conduct a thorough diagnostic evaluation, including a detailed medical, psychological, developmental, family, treatment and dietary history, physical exam, and, as indicated, a complete blood count, electrolyte/mineral screen, and possibly a serum lead assessment and electroencephalogram.

“Blood tests can be very helpful right at the start to identify any deficiencies or excessive amounts of certain vitamins, minerals and other chemicals in the blood system that we can try to change,” said Lofthouse.  “An EEG may indicate whether neurofeedback can be helpful.”

Melatonin and Omega-3 Fatty Acids

Hendren shared his perspective on some orally ingested CATs.

“In my practice and based on the literature reviewed in our article, I recommend melatonin for patients,” he said.  “Most often melatonin is for kids who are having trouble falling asleep, but it also has some properties that help the body regulate itself, and it may have an immune effect  as well, making it worth taking by every patient.”

He starts the dosage at 2 or 3 mg/day and then gradually increases it up to 9 mg/day if necessary for sleep.  It can be given 30 minutes before bedtime for its sedating effects, he said, or given 2 to 3 hours before bedtime to help reset the body’s sleep clock.   Rossignol and Frye, he added, published an excellent review and meta-analysis of 35 studies. 3

Good randomized controlled trials exist, Hendren added, suggesting that omega-3s (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA])are helpful for autism,. The thought is that omega-3s have a neuroprotective effect and help neurons grow in a healthier way.

At UCSF, Hendren and his team have completed  a pilot randomized controlled trial to determine the feasibility and initial safety and efficacy of omega-3 fatty acids (1.3 g/day) for the treatment of hyperactivity in 27 children aged 3 to 8 years with ASD. After 12 weeks, hyperactivity, as measured by the Aberrant Behavior Checklist, improved 2.7 (± 4.8) points in the omega-3 group compared to 0.3 (± 7.2) points in the placebo group (p = 0.40; effect size = 0.38). 4  Currently, Hendren and the primary author of the first study are conducting another study involving participants in the Interactive Autism Network (http://www.IANresearch.org).

Vitamins, Probiotics and Enzymes

Hendren recommends giving high potency vitamins to kids with ASD because some evidence suggests that children with autism tend to be deficient in certain nutrients.  He also suggests possible supplementation with vitamin D.

“There is a lot of evidence that kids with autism have low vitamin D levels, so it is worth checking those levels and possibly giving them 2000 IU/day,” he said.  “Often kids can handle 2000 to 4000 IUs without any adverse effects.”

Currently, Hendren and UCSF team are conducting an open-label trial investigating the tolerability of  high-dose vitamin D3 supplementation and its possible efficacy in improving the core symptoms of autism, including sociability, eye contact, anger outbursts and sleep.

In a study funded by Autism Speaks, Hendren and others are also conducting a double-blind, placebo-controlled trial of subcutaneous methyl B12 on metabolic and behavioral measures in children with autism.

“We have reported some of our early findings in poster sessions which suggested a strong trend towards positive outcomes for a subgroup of about one-third of the kids,” he said.

For children with ASD and gastrointestinal problems, Hendren suggests that probiotics and pancreatic digestive enzymes are worth considering.
Hendren and his team are involved in a phase III randomized double-blind, placebo-controlled trial of a pancreatic enzyme for the treatment of core symptoms of autism.

Neurofeedback

Lofthouse and his team are specifically looking at neurofeedback for ASD.  In October of 2012, Lofthouse spoke about the promise of neurofeedback for attention-deficit/hyperactivity disorder (ADHD) and ASD at the an American Academy of Child and Adolescent Psychiatry (AACAP).

There are only 3 randomized controlled trials and 1 double-blind and 1 single-blind, said Lofthouse.  He added that while there are few scientifically rigorous studies on neurofeedback for ASD, “because of the EEG abnormalities associated with ASD, it has a lot of potential.”

The reviewed studies  found significant improvements in neuropsychological set shifting skills, sustained attention, speech/language communication and sociability, among others.6-8

Outgrowing Autism?

A recently published National Institutes of Health Study of 112 children suggested that some children might possibly outgrow autism. Fein et al. studied 34 children identified as optimal outcome, who had been diagnosed with autism in early childhood but went on to function as well as other children in their classes, 44 children identified as having “high-functioning” autism and 34 typically developing children.9

The 34 optimal outcome (OO) participants “had a clear documented
history of ASD, yet no longer met criteria for an ASD as per the Autism Diagnostic Observation Schedule (ADOS) and clinical judgment,” they concluded.
Asked about the study, Lofthouse said, “I don’t doubt that some kids can grow out of it.  It is a relatively new area and finding. “

“Some of these kids that grew out of autism may have done so because they had really excellent treatment early on,” he added.  “At this point we don’t know which kids will outgrow these disorders and which kids won’t… when they are having symptoms that are impairing their lives; the safe bet is to immediately treat them with the best conventional treatments..  These kids are moving targets, their brains are constantly developing, so it is important to reassess them periodically to see if their impairments have lessened and whether they still require a particular type and frequency of treatment, regardless of whether it is a CAT, a prescription drug or therapy.”

References

1.  Lofthouse N, Hendren R, Hurt E, et al. A review of complementary and alternative treatments for autism spectrum disorders.  Autism Res Treat. [Epub 2012; Nov 28.]
2.  Hanson E, Kalish LA, Bunce E, et al.  Use of complementary and alternative medicine among children diagnosed with autism spectrum disorder. J Autism Dev Disord. 2007;37(4):628-636.
3.  Rossignol DA, Frye RE. Melatonin in autism spectrum disorders: a systematic review and meta-analysis.  Dev Med Child Neurol. 2011;53(9):783-792.
4.  Bent S, Bertoglio K, Ashwood P, et al. A pilot randomized controlled trial of omega-3 fatty acids for autism spectrum disorder.  J Autism Dev Disord. 2011;41(5):545-554.
5.  Coben R, Linden M, Myers TE. Neurofeedback for autistic spectrum disorder: a review of the literature.  Appl Psychophysiol Biofeedback. 2010;35(1):83-105
6.  Holtmann M, Steiner S, Hohmann S, Poustka L, et al. Neurofeedback in autism spectrum disorders. Dev Med Child Neurol. 2011;53(11):986-993
7.  Pineda JA, Brang D, Hecht E, et al.  Positive behavioral and electrophysiological changes following neurofeedback training in children with autism. Res Autism Spectr Disord.  2008;2(3):557-581.
8.  Kouijzer MEJ, van Schie HT, de Moor JMH, et al.  Neurofeedback treatment in autism.  Preliminary findings in behavioral, cognitive, and neurophysiological functioning.  Res Autism Spectr Disord.  2010:4(3)386-399.
9.  Fein D, Barton M, Eigsti IM, et al.  Optimal outcome in individuals with a history of autism.  J Child Psychol Psychiatry. 2013;54(2):195-205.

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