Given the severe and chronic problems associated with Autism Spectrum Disorders (ASD) and the limitations of available treatments, there exists a large public health need for additional interventions. As more parents are inquiring about complementary and alternative treatments (CATs), both parents and practitioners require up-to-date information about them and whether and how to integrate them into treatment. After presenting data on CAT usage patterns for ASD, we review 13 ingestible (i.e., orally administered) and 6 noningestible (i.e., externally administered) CATs for ASD. For each CAT we briefly describe its definition; rationale for use; current research support, limitations, and future directions; safety issues; and whether we currently recommend, not recommend, or find it acceptable for the treatment of ASD. We conclude this paper with recommendations for future research and ten clinical recommendations for practitioners.
Many treatments (Txs) have been proposed for Autism Spectrum Disorders (ASD) with the most effective being combined Tx involving specialized and supportive educational programming, communication training (e.g., speech/language therapy), social skills support, and behavioral intervention [
Risperidone (Risperdal) and aripiprazole (Abilify) are the only FDA-approved medications for ASD, and they are approved only for the Tx of irritability in 5–16 year olds with ASD. No medications are currently established to treat ASD core symptoms. “Off-label” medications are often prescribed for cooccurring behaviors such as inattention, impulsivity/hyperactivity, sleep problems, repetitive/perseverative behaviors, anxiety, mood, agitation, aggression, and disruptive and self-injurious behaviors but may have significant side effects [
The National Center for Complementary and Alternative Medicine (NCCAM) defines complementary and alternative medicine (CAM) as “a group of diverse medical and health care systems, practices, and products that are not generally considered to be part of conventional medicine” [
Global studies report rates of CAT use for ASD range from 32 to 87% in the US [
In the US, most parents report concerns regarding medication safety (84%) and side effects (83%) as the main reasons for choosing CATs [
Regarding the number of CATs used in 2008, the Interactive Autism Network’s (IAN) ongoing online survey of 1000’s of U.S. parents reported a total of 381 different Txs, most of which are CATs, being used at any one time, with an average of five Txs per child (min. = 0, max. = 56 concurrent Txs!), >50% receiving ≤4 Txs, and 5% receiving no Tx at all [
In terms of which specific CATs are used, applying NCCAM’s five categories, Hanson et al. [
There is limited scientific evidence of efficacy for some CATs, but research on CATs for ASD is imperative because key safety and efficacy questions remain for the majority [
As of December 2011, there have been 14 comprehensive reviews of ASD CATs in Medline and PsychInfo [
The CATs summarized in this paper (and in Tables
Commonly used complementary and alternative treatments (CATs) for autism spectrum disorders (ASD).
Name | Rationale/mechanism | Data type | Significant improvements and |
Potential adverse effects | SECS | Recommendation* |
---|---|---|---|---|---|---|
|
||||||
Melatonin | ↑ sleep | 5 DB PBO |
Sleep duration and, overall sleep, sleep onset latency, | Minimal to none | S, E, C, S | R for sleep |
B6/Mg | Correct deficiency | 6 DB PBO |
Social interaction, communication, and repetitive behavior (in some but not all RCTs) | >200–300 g neuropathy diarrhea | S for <200 mg, |
A |
B12 | Correct deficiency | 1 DB RCT | Some functioning and behavior | None reported | S, S but not C, E | NR b/c not E and sparse data |
Multivitamin/mineral | Nutritional status associated with ASD sxs | 2 DB PBO |
Sleep, gastrointestinal, functioning, hyperactivity, tantrums, and self-injury | None reported | S (if RDA/RDI) |
R for RDA/RDI if poor diet; |
Folic acid | Genetic abnormality | 1 open label | Receptive and expressive language | None reported | S, E, C, S | A |
Omega-3 | Correct deficiency | 2 DB RCTs |
Stereotypy, hyperactivity, and inappropriate speech | None reported | S, E, C, S | A |
Probiotics and GI medication | Remove toxins |
1 DB PBO |
None | None reported | Safe, E | A when GI problems |
Iron supp. | Correct deficiency | Open trial | Restless sleep | None reported | S (only if low Fe) |
A if iron deficiency confirmed |
Chelation |
|
1 DB PBO |
Language, cognition, and sociability | Renal/hepatic toxicity, fatigue, diarrhea | Sometimes not safe; not cheap | A if heavy metal toxicity confirmed |
L-Carnosine | Neuroprotective |
1 DB PBO |
ASD sxs and receptive/expressive language | Hyperactivity and excitability | E, Sensible | Possibly A |
Ascorbic acid (vit C) 90 mg/kg | Corrects redox balance | 1 DB PBO |
Repetitive behavior | Can interfere with B12 absorption | E, C, S | NR in these doses |
Cyproheptadine | High 5-HT levels | 1 DB PBO |
ASD sxs | None reported | Some risk | NR b/c some risk and sparse data |
Immune therapies | Immune deficiencies | 6 open label | Some ASD sxs | None reported | Some risk | NR b/c some risk |
| ||||||
|
||||||
Massage | ↑ attachment and |
5 RCTs |
ASD sxs, sleep, social relatedness, social communication, speech rate, receptive language and ADHD sxs, sensory issues repetitive beh., anxiety, disruptive beh. | Not examined | S, E, C, S | R |
Acupuncture | Unblocking flow of energy (“qi”) | 3 RCTs** |
Attention, receptive language, overall functioning, self-care, and communication | Few or mild possible infection, bleeding | S, E, S | A |
Exercise |
|
8 within-sub. | Self-stimming and academic scores | Not examined | S, E, C, S | A |
Music therapy | ↑ verbal and nonverbal communication and engagement | 2 randomized counterbalan. |
Imitating signs and words, eye-contact turn-taking, joint attention, and nonverbal communication | Not examined | S, E, S | A |
Animal-assisted |
↑ attachment | 1 RCT |
Playful mood, focus, language use and social-awareness, interaction and motivation | Not examined; possible bites, scratches, accidents | S, E, S | A b/c may not be C |
Neurofeedback | EEG changes | 3 RCTs |
Attention, set-shifting, speech/language, sociability, health/physical behavior, reciprocal social interaction, communication, sensory cognitive awareness ↑ EEG mu suppression and |
Not examined | S, S | NR b/cnot C |
Note. SECS: safe, easy, cheap, and sensible; *recommendations for an individual and monitored patient trial following procedure reported in study: R: recommended, A: acceptable, NR: not recommended; DB: double blind; PBO: placebo controlled; RCT: randomized clinical trial; X-over: crossover; sxs: symptoms; SB: single blind; **3 English-language articles that we could review thoroughly but 9 RCTs in Chinese only also exist.
Randomized controlled trials of ingestible complementary and alternative treatments for autism spectrum disorders (ASD).
Tx | Author, year |
|
ASD type and |
Control | Tx dose*, |
Results |
---|---|---|---|---|---|---|
Melatonin | McArthur et al. 1998 [ |
9, 4–17 |
Rett/N |
PBO | 2.5–7.5 mg |
Sleep latency2,5 |
Garstang et al. 2006 [ |
11, 5–15 |
ASD/N |
PBO | 5 mg |
|
|
Wasdell et al. 2008 [ |
51 (16 ASD) |
ASD/N |
PBO | 5 mg |
Sleep latency5 |
|
Wirojanan et al. 2009 [ |
18 (12 ASD) |
ASD/N |
PBO | 3 mg |
Sleep latency2,5 |
|
Wright et al. 2010 [ |
20, 4–16 |
ASD/N |
PBO | 2–10 mg |
Sleep latency2 |
|
| ||||||
B6/Mg | Martineau et al. 1985 [ |
16, 3–14 |
AD/Y | Mg only | B6: 30 mg/kg |
Overall improved in both conditions3 |
Martineau et al. 1985 [ |
21, 3–14 |
AD/Y | PBO | B6: 30 mg/kg |
Improved ASD3 |
|
Martineau et al. 1985 [ |
35, 3–14 |
AD/Y | PBO | Mg: 10–15 mg/kg |
No change ASD3 |
|
Martineau et al. 1985 [ |
37, 3–14 |
AD/Y | PBO | B6: 30 mg/kg/ |
No change ASD3 |
|
Lelord et al. 1981 [ |
21, 3–16 |
Autistic Beh. N | PBO | 625–1125 mg B6 |
Evaluated if response/nonresponse status from OL remain in DB |
|
Findling et al. 1997 [ |
12, 3–17 |
AD/Y | PBO | 30 mg/kg B6 |
ASD3: ns | |
| ||||||
B12 | Bertoglio et al., 2010 [ |
30, 3–8, |
AD/Y | PBO | 64.5 mg/kg injection, every 3rd day, 12 wks | ASD3: ns |
| ||||||
Micronutrients | Adams and Holloway 2004 [ |
20, 3–8 |
ASD/N |
PBO | 3 mL/5 lbs |
Communication2: ns |
Adams et al. 2011 [ |
141, 5–60 |
ASD/N |
PBO | Formulated by Yahoo Health | ASD2: ns |
|
| ||||||
Omega-3 | Amminger et al., 2007 [ |
13, 5–17 |
AD/Y | PBO | 840 mg EPA, |
Irritability3: ns |
Bent et al. 2011 [ |
27, 3–8 |
ASD/Y | PBO | 700 mg EPA, |
Hyperactivity2: ns | |
| ||||||
Probiotics | Munasinghe et al. |
43, 3–8 |
ASD/Y | PBO | Up to 9 caps |
ASD2: ns |
| ||||||
L-Carnosine | Chez et al. 2002 [ |
31, 3–12 |
ASD/Y | PBO | 800 mg |
ASD2 |
| ||||||
Ascorbic Acid | Dolske et al. 1993 [ |
18, 6–19 |
AD/Y | PBO | 90 mg/kg |
Repetitive beh4 |
| ||||||
Cyproheptadine | Akhondzadeh et al., 2004 [ |
40, 3–11 |
AD/Y | Haloperidol + PBO | 0.2 mg/kg Cypro + Haloperidol 0.5 mg/kg |
ASD2 |
| ||||||
Gluten-Free/ Casein-Free Diet (GFCF) | Knivsberg et al. 2003 [ |
20, |
AD/N |
No Tx | GFCF diet |
Social2 |
Elder 2006 [ |
15, 2–16 |
ASD/Y | Typical diet | GFCF diet |
ASD3: ns | |
Whiteley et al. 2010 [ |
72, 4–10 |
ASD/N |
No Tx | GFCF diet |
Social: ns2,4, |
|
Johnson et al. |
22, 3–5 |
ASD/Y | Healthy diet | GFCF diet |
ADHD2: |
Note: AD: Autistic Disorder, ASD: Autism Spectrum Disorder; ASP: Asperger’s Disorder; unk: unknown; Tx: treatment; dx: diagnosis; DSM dx: Y: yes (children diagnosed according to DSM-III or DSM-IV symptoms of ASD) and N: no (children not specifically diagnosed by DSM criteria; ADOS: Autism Diagnostic Observation Schedule; ADI-R: Autism Diagnostic Interview Revised); PBO: placebo; wk: week; x-over: cross-over; WL: Wait List; ns: nonsignificant; *treatment dosages are per day, unless otherwise specified; OL: open label; beh: behavior; vocab: vocabulary; communic: communication; results superscripts indicate the method of assessment: 1teacher/staff, 2parent, 3therapist/clinician, 4observation, 5psychometric/standardized testing; **significance values not included in the text; ***
Randomized controlled trials of noningestible complementary and alternative treatments for autism spectrum disorders (ASD).
Tx | Author, year |
|
ASD type and DSM Dx | Tx info | Tx dose, duration | Control | Results |
---|---|---|---|---|---|---|---|
Massage | Field et al. 1997 [ |
22, |
AD/Y | Given by staff at school | 30 min/wk, |
Attention (games) | ASD1 |
Escalona et al. 2001 [ |
20, 3–6 |
AD/Y | Parent massage at bedtime | 15 min/day, |
Reading at bedtime | ADHD1,2,4 |
|
Silva et al. 2007 [ |
15, 3–6 |
AD/Y | Therapist 2x/wk |
15 min/day |
WL | Sensory2 |
|
Silva et al. 2009 [ |
46. 3–6 |
AD/N (eligible for AD services) | Therapist 2x/wk |
15 min/day |
WL | Social/commication1,2 |
|
Piravej et al. 2009 [ |
60, 3–10 |
AD/Y | SI Tx + massage |
2 hrs/week |
SI Tx only | ADHD1,2: ns |
|
| |||||||
Allam et al. 2008 [ |
20, 4–7 |
AD/Y | Scalp acup + speech Tx | 2x/wk speech |
Speech Tx only | ADHD3 |
|
Acupuncture | Wong and Sun 2010 [ |
50, 3–11 |
AD/Y | Tongue acup | 5x/wk |
Sham | Social2,5: ns |
Wong et al. 2010 [ |
55; 3–18 |
ASD/Y | Electro acup | 3x/wk |
Sham | Social: ns2,3, |
|
| |||||||
Animal assist | Bass et al., 2009 [ |
34, 4–10, |
ASD/Y | Equine Tx | 1 hour/wk |
WL | Sensory2 |
| |||||||
Music therapy | Buday, 1995 [ |
10, 4–9 |
AD/unk | Structured | 5 sessions | Rhythm therapy | Communication4 sig (in Tx session) |
Kim et al. 2008 [ |
20, 3–6 |
AD/Y | Music therapy |
30 min/wk |
Play with toys | Social: ns2,3, |
|
| |||||||
Neurofeedback | Pineda et al. 2008 [ |
8, 7–17 |
ASD/N |
↑ Mu suppression | 90 min/wk |
Sham | ADHD5 |
Pineda et al. 2008 [ |
19, 7–17 |
ASD/N |
↑ Mu suppression | 90 min/wk |
Sham | Improvement in ADHD5, social2, and communcation2; not stated if significant |
|
Kouijzer et al. 2010 [ |
20, 8–12 |
ASD/Y | Excess |
40 txs, |
No Tx | ASD: ns1, ns2, |
Note: AD: Autistic Disorder, ASD: Autism Spectrum Disorder; DSM Dx: Y: yes (children diagnosed according to DSM-III or DSM-IV symptoms of ASD) and N: no (children not specifically diagnosed by DSM criteria; diagnosis method listed in parentheses); Tx: treatment; dx: diagnosis; ADOS: Autism Diagnostic Observation Schedule; ADI-R: Autism Diagnostic Interview Revised; wk: week; SI: sensory integration; acup: acupuncture; WL: Wait List; ns: nonsignificant; results superscripts indicate the method of assessment: 1teacher/staff, 2parent, 3therapist/clinician, 4observation, 5psychometric/standardized testing; **significance values not included in the text.
Complementary and alternative treatments for autism spectrum disorders either without positive effects in randomized control trials (RCTs) or without sufficient evidence to evaluate (listed alphabetically).
Without positive effects in RCTs | ||
| ||
Auditory integration therapy [ |
||
| ||
Without sufficient evidence to evaluate | ||
| ||
Allithiamine |
Gentle teaching |
Sensory integration therapy |
Note: (1) List of CATs from Medline/PsychINFO reviews and Interactive Autism Network (IAN) research online parent questionnaire of treatments utilized for child with ASD
(2) Although included in the IAN study, the following were not included in our CAT review because they are in the realm of conventional treatments such as speech, special education, and cognitive and behavior therapy: Augmentative and Alternative Communication (AAC), Floortime (from Difference, Relationship-based approach), Discrete Trial Training, Language Preschool, Lifeskills and Education for Students with Autism and other Pervasive Behavioral Challenges (LEAP), Picture Exchange Communication System (PECS), Pivotal Response Training (PRT), Rapid Prompting Method, Relationship Development Intervention (RDI), Self-Injurious Behavior Inhibiting System (SINIS), Social Stories, Treatment and Education of Autistic and Communication-Handicapped Children (TEACCH), Toilet Training, and Visual Schedules.
(3) Some of CATs in the table have evidence of positive effects in other disorders, but not for ASD. This does not necessarily mean they are without merit, just that there is not enough current evidence of a positive effect for ASD.
* Although we respect individual’s religious views, prayer, psalms, and spiritual practices, which were identified by parents as utilized treatments in the IAN survey, these approaches do not currently have any scientific evidence of a positive effect for ASD symptoms.
Melatonin is an endogenous neurohormone released by the pineal gland in response to decreasing levels of light, it causes drowsiness, and sets the body’s sleep clock. ASD has a high frequency of sleep problems and melatonin is increasingly used to help children with ASD fall asleep [
Unfortunately, small sample sizes, variability in sleep assessments, and lack of follow-up limit the conclusiveness of these studies but, overall, melatonin is one of the best studied CATs for ASD. Future research directions include using placebo controlled or comparative effectiveness trials to determine which sleep intervention works best for which child, larger samples identifying inexpensive Tx targets to better match melatonin and other Txs to the individual with ASD, combining melatonin with other Txs for insomnia and ASD, and, based on one of the author’s clinical experiences, identifying those with mid and late insomnia who might respond to higher doses of melatonin. Melatonin is sensible, easy, cheap, and safe; therefore, we recommend a trial of melatonin for sleep delay problems in ASD.
One of the oldest and best studied dietary supplementation strategies for ASD is high-dose pyridoxine (vitamin B6) and magnesium (Mg), presumably correcting a metabolic aberration that requires higher than usual intake of those essential nutrients. Improvements maybe noted in social interactions, communication, and stereotyped, repetitive behaviors although the measurements for these symptoms are impressionistic. Pfeiffer et al. [
In a prospective open trial [
However, a double-blind placebo-controlled study reported no benefit in 10 children with autism treated for 10 weeks [
In sum, the evidence for B6 + Mg from over 25 studies remains rather equivocal, a bit more positive than negative. Despite encouraging results from open studies, those from RCTs are less promising. Limitations of extant research to be addressed by future research include small samples, inconsistent diagnostic methods and assessments, lack of evidence for mechanism, and lack of blinding. Future studies should involve larger, double-blind placebo-controlled trials using a biomarker of Tx response such as B6 and Mg levels. It is probably safe if the daily doses of B6 are kept well below a gram and daily doses of Mg are not over 200–300 g. Higher doses risk neuropathy from B6 or diarrhea from Mg. It is not expensive or especially difficult. It is credible that the genetic aberration resulting in autistic symptoms might involve a metabolic need for more than usual intake of these two nutrients. Therefore, a carefully monitored trial with moderate doses passes the SECS criterion and is acceptable.
Deficiency of methyl B12 (methylcobalamine) may occur in some people with ASD due to poor dietary intake, poor absorption, or metabolic dysregulation. Methyl B12 is a vital cofactor for the regeneration of methionine from homocysteine by providing methyl groups for the transmethylation and transsulfuration metabolic pathways. Reduced synthesis of the products of the transsulfuration pathway, including cysteine and GSH, may consequently lead to decreased antioxidant capacity. Glutathione dysregulation may be of particular significance, as GSH is a key antioxidant responsible for minimizing macromolecular damage produced by oxidative stress. Improvements may be noted in social relatedness, language, and behavior problems. Methyl B12 is often administered at high dose subcutaneous injections every 2 to 3 days. There are no studies of oral or nasal methyl B12, which are thought to be less effective because they do not keep consistently high levels.
James et al. [
The study mentioned above showing the response to methyl B12 of a subgroup of children with autism is the only published RCT but a new RCT from the same group is being presented at national meetings and will be completed in early 2013. Additional research is needed to delineate a subgroup of responders and ascertain a biomarker of response to methyl B12. Subcutaneous injectable methyl B12 does not meet SECS criteria because it is invasive (not easy) and based on only one published, controlled trial. But it does appear safe from this and other reports. While initial studies are promising for a subgroup of children with ASD and supplementation is well tolerated, additional study is needed to determine whether this is a recommended Tx for ASD.
Although multivitamin and mineral levels generally are not found to be abnormal in children with autism, biomarkers of nutritional status have been reported and are found to be associated with autism severity [
A RCT of oral vitamin/mineral supplement for 3 months with 141 children and adults with ASD showed improved nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH [
A clinic study reported on 44 patients with ASD treated with the vitamin-mineral mix at parent preference (6 were actually treated with prenatal vitamins, available on Medicaid prescription, to save the family money) [
In summary, there is limited evidence for the efficacy of vitamin and mineral supplements for ASD although there is widespread usage. The promising results from the open label and 2RCT warrant larger, placebo-controlled RCTs with pre- and postmeasures of vitamin, mineral, and metabolic status. Meanwhile, multiple-vitamin and micronutrient supplementation passes the SECS criterion as long as no ingredient is above the upper tolerable limit. It is recommended for those with a restricted or idiosyncratic diet and those with poor appetite, and is acceptable for all others.
Folic acid has been considered because a polymorphism in the gene for methylenetetrahydrofolate reductase (MTHFR C677T) doubles the risk of autism [
Omega-3 long-chain fatty acid supplementation is reasonable to consider because omega-3 fatty acids are essential to brain development [
There have been 4 open trials [
With only 2 small placebo-controlled RCTs totaling 38 children, all 3 without statistically significant effects (possibly a power issue), the evidence is rather thin for omega-3 supplementation in ASD. Limitations to be addressed by future studies include sample size, necessary duration of Tx, dose, and ratio of EPA to DHA (one of the failed pilot studies used only DHA). Nevertheless, it is safe, easy, cheap, and sensible in light of the known nutritional need for omega-3 fatty acids and their benefit for cardiovascular health, ADHD, and mood disorders. Thus, it passes the SECS criterion and is acceptable for ASD while awaiting definitive research.
There is increasing evidence for a gut-brain connection associated with at least some cases of ASD [
A double-blind placebo-controlled trial using crossover design over 6 months for 43 children with ASD, aged 3–8 years, did not show any clinically significant improvement of ASD symptoms with enzyme use [
While there is no published evidence that probiotics or digestive enzymes are effective in treating ASD, their use for treating GI symptoms and their safety profile suggest that they might be considered in treating individuals with ASD and GI symptoms.
Low serum ferritin and low iron intake are reported in some children with ASD [
Chelation is a process for removing heavy metals from the blood and is used in treating ASD based on the unproven theory that ASD is caused by heavy metal toxicity. The accumulation of heavy metals, particularly mercury, is theoretically due to either the body’s inability to clear the heavy metals or to increased exposure or both. Detoxification involves courses of oral DMSA (2, 3 dimercaptosuccinic acid) with periodic elemental analysis of urine from subjects and controls. To be successful, detoxification Tx requires two prerequisite Txs that must be successful—clearing the gut of harmful dysbiotic flora, and bolstering metabolism with essential nutrients so that the individual can tolerate detoxification.
Two related studies have been published [
Regarding anecdotal evidence, of all the drug, diet, and nutritional therapies listed on the ARI Survey, detoxification is reported to help the highest percentage of individuals with ASD (71%) and it “worsened” only 3%, the second lowest percentage. Those who favor chelation are clinicians who are knowledgeable and experienced with it.
However, chelation is controversial and the Institute of Medicine (IOM) recently warned of unspecified “risks.” Renal and hepatic toxicity is possible with oral agents. Most common side effects are diarrhea and fatigue. Less common side effects include abnormal complete blood count (CBC), Liver Function Tests (TFTs), mineral abnormalities, seizures, sulphur smell, regression, GI symptoms and rash. Therefore, we only recommend chelation for ASD if heavy metal toxicity is confirmed.
L-Carnosine has been considered because it can be neuroprotective or improve function of frontal lobes. In an 8-week double-blind RCT with 31 children aged 3–12 with ASD, l-carnosine (800 mg/day) but not placebo showed statistically significant improvements on the Gilliam Autism Rating Scale (total score and the Behavior, Socialization, and Communication subscales) and the Receptive One-Word Picture Vocabulary test (all
The rationale for ascorbic acid (vitamin C) supplementation in large doses is that it blocks binding to DA receptors and possibly corrects redox balance, leading to correction of metabolic stress that may contribute to autism symptoms. In a 20 wk double-blind crossover following a 10-week single-blind ascorbate run-in, 18 residential patients aged 6–19 years were randomized to ascorbate-placebo or placebo-ascorbate order [
Because ascorbic acid doses this large could interfere with B12 absorption, there is some risk, which could be ameliorated by additional B12, but the amount needed is not established. Due to this safety issue (as well as efficacy) ascorbic acid in these megadoses requires further study, does not currently pass the SECS criterion, and is not recommended.
High levels of 5-HT have been reported in ASD so Tx with cyproheptadine, a 5-HT2 antagonist, has been proposed. A double-blind, placebo-controlled study with 40 children using haloperidol in each Tx arm found that cyproheptadine was well tolerated and showed greater benefit on two scales (ABC and CARS) than did haloperidol plus placebo [
Evidence is accumulating that ASD subgroups have immune deficiencies and autoimmunity [
Currently there are six published open-label trials of IVIG Tx with ASD. Other than Gupta’s study [
This CAT involves the manipulation of superficial layers of muscle and connective tissue to enhance bodily functioning, relaxation, and well-being. It has been suggested for ASD to increase connectivity to others and reduce overarousal. Five RCTs (all single blind) have examined massage therapy [
Based in Traditional Chinese Medicine, acupuncture involves the systematic insertion and manipulation of thin needles into the body, via 400 acupoints, to improve health of body/mind by unblocking the flow of qi (“energy”). For ASD, there are three RCTs (1 DB sham controlled) published in English using scalp [
Research limitations and future directions include the lack of double-blind, sham-controlled RCTs, long-term follow-up, standard Tx protocols, use of standard Tx outcome measures, and monitoring of possibly confounding concomitant Txs. As acupuncture appears safe and seems sensible (from a Traditional Chinese Medicine perspective) and easy, it is acceptable for ASD if not too expensive.
Exercise programs have been found to be beneficial for a variety of psychiatric and developmental disorders [
Music therapy involves structured and unstructured individual and group sessions with and without a leader involving playing and/or listening to music. It has been used to Tx ASD because of its potential for assisting communication, joint attention, expression, engagement, and relationships with the environment [
AAT involves structured and supervised therapeutic interaction with animals, which are seen as transitional objects for initial bonding for individuals with ASD before generalizing this attachment to people. Although there are many case studies of AAT, only four studies have recruited multiple subjects, with the most recent being the only RCT [
NF “trains” the brain to improve self-regulation of itself by providing it with real-time video/audio information about its EEG activity. It has been suggested for the Tx of ASD because QEEG studies indicate over- and underconnectivity [
Kouijer et al. [
Based on these 3 studies, the following clinical improvements are expected with sustained attention and set-shifting skills; parent-rated speech/language communication, sociability, health/physical behavior, reciprocal social interaction, communication skills, and, possibly, sensory/cognitive awareness. Research limitations and future directions include the lack of a large double-blind RCT sham study with follow-up, use of standard Tx outcome measures, monitoring of adverse effects, and concomitant Txs. Even though NF appears safe (although not empirically examined) and seems sensible, it is not easy or cheap and is therefore not recommended at this time.
Finally, the following CATs (with cited reviews) are not recommended because they failed to show positive effects across several RCTs: Auditory Integration Therapy [
Nineteen CATs were reviewed, including 13 ingestible and 6 noningestible CATs. Research on these CATs is extremely varied, ranging from case studies to double-blind, sham-controlled RCTs, with and without significant results. Their safety, easy of use, sensibility, and expense (SECS) also vary considerably. Currently, we would only recommend two ingestible and one noningestible CAT, melatonin and RDA/RDI multivitamin/mineral (for those with a limited diet and/or poor appetite), and massage therapy, respectively. However, the following CATs are considered acceptable and worth considering for a short, monitored trial, if conventional Txs for ASD and the two recommended CATs have been given a reliable trial and found ineffective. For ingestible CATs: B6 and magnesium, multivitamin/mineral (even without a restricted/idiosyncratic diet and/or poor appetite, as long as no ingredient is above tolerable limit), folic acid, omega-3, L-Carnosine, probiotics and GI medication (only for ASD patients with GI symptoms), iron supplementation (only for those with low serum ferritin), and chelation (only for those with confirmed heavy metal toxicity). For noningestible CATs: Acupuncture, exercise, music therapy, and animal-assisted therapy.
Although published after our literature search, we feel it is important to mention N-Acetylcysteine (NAC) as an ingestible CAT that has great potential. NAC is a glutamatergic modulator and antioxidant and was recently examined in a 12-week, double-blind, randomized, placebo-controlled study in children with autistic disorder [
This review of ingestible and noningestible CATs for ASD indicates to us that this promising field is in need of more double-blind, placebo/sham controlled RCT’s with long-term follow-up and reliably diagnosed samples of participants with ASD, using standard Tx outcome measures, while continually monitoring potential adverse effects and changes in concomitant Txs. We also encourage definitive trials and replications of the more promising CATs that may have some advantage (benefit-risk ratio) over standard Txs if proven effective. For well-considered hypotheses for which there are no pilot data, we would suggest controlled clinical trials when easy and cheap and open pilot trials when controlled trials would be expensive or difficult. Finally, to fully realize the potential of these CATs, studies are required to compare them to established Txs (i.e., behavior modification and medicine) to examine incremental effects to designate CATs as complementary Txs and similar effects to designate CATs as alternative Txs.
Although current research on CATs for ASD is limited, the Tx needs of individuals cannot always wait for science to improve. So for those who do not respond completely to evidence-based Txs, practitioners are often expected to advise patients about CATs. As many families may also experiment with CATs by themselves, especially if they sense a practitioner’s reluctance to consider CATs, we believe it is clearly better for individual trials to be guided professionally. In that respect, we offer practitioners the following 10 clinical recommendations. As many CATs target specific causes, they should be Clinicians and parents/patients need to request data/evidence as many commercially advocated Txs claim to have scientific proof, but can provide only anecdote, case history, or testimonial information. In Tx outcome research, comparisons to established Txs are not convincing unless assignment is random to control for selection effects and associated expectations due to subjects and parents choosing the preferred Tx, nonrandom subject experiences (i.e., subject history), regression to the mean, maturation, practice with assessments, or an interaction of any of these factors. Failure to find a significant difference from an established Tx does not make the Tx equal or effective because a small sample can easily fail to find a significant difference when one really exists. For some individuals, a CAT may work better than established Tx even though it is not demonstrated by group averages. The decision to try a CAT in an individual case depends partly on data, SECS criterion, and accessibility and response to conventional Txs. Diverting patient resources (money, time, and effort) to a Tx that does not work is a risk that needs to be considered for the patient and other family members. Change one thing at a time and monitor results and side effects with specific ASD rating scales or a simple graph (e.g., no. of weeks of Tx along the Patients and their families should be encouraged to discuss with their prescribing doctor all ingestible CATs, even “natural” herbs, to identify any possible interactions with currently prescribed medications or other ingestible CATs. Patients (as developmentally appropriate) and their families should be provided with biopsychosocial information or psychoeducation about ASDs and their Tx. As “knowledge is power,” psychoeducation, which is actually another form of complementary Tx, can give “power” to help people to improve cognitive and emotional control over a condition; alter cognitive schema to correct past misinformation and prevent future errors; access and collaboratively utilize cost-effective mental health, educational, and community services. Psychoeducation resources can be accessed from: