Autism Spectrum Disorders

Autism.jpg (jpg, 118.34 KB) [1]

This section contains a review of treatments that have been used in individuals with Autism Spectrum Disorders (ASD). The review includes conventional treatments that are often covered on other websites, some integrative therapies that may offer potential benefit, and a couple of alternative therapies that pose some risk.  

ASD symptoms and severity vary from patient to patient. Thus, there is no right way to treat ASD. Our purpose is not to endorse or suggest the use of specific therapies, but to provide information about the evidence, or lack-there-of, along with potential risks/benefits of various treatment modalities. We recommend, as always, that you talk to your family's healthcare providers about any options you are interested in pursuing.

What are Autism Spectrum Disorders?

Individuals with ASD have difficulty with social interactions and communication, as well as restricted, repetitive behaviors, interests, or activities. These symptoms usually appear before age three. ASD is thought of as a "spectrum" disorder; different people with ASD may have very different symptoms, levels of severity, strengths, and challenges.

Rate of ASD

The rate of children diagnosed with ASD is increasing. The Centers for Disease Control and Prevention (CDC) reports that one in 110 children in the U.S. is affected by ASD. This rate has increased since 2002, when it was one in 166, or since 1999, when it was one in 1,000. Much of this increase is explained by changes in diagnostic practice, including:

• Broadening the definition of ASD to include higher-functioning children
• Increased accuracy in the diagnosis of ASD (particularly for children who previously may have been diagnosed with intellectual disability)
• Increased awareness of the disorder
• Earlier identification of young children

However, we cannot rule out that there is a true increase in the risk for ASD.

Diagnosis

There is an increasing body of evidence to show that ASD is a neurobiological disorder resulting from several causes, but with a strong genetic basis. However, to date, no biological marker exists to "diagnose" ASD.

A diagnosis of ASD is based on behavioral criteria requiring extensive neuropsychological evaluation, which assesses cognitive, developmental, and language abilities, as well as adaptive behaviors or life skills. [2]

See general ASD resources [2].

What are the Conventional Treatments for Autism Spectrum Disorders?

While the following section focuses on children, a great number of individuals diagnosed with ASD are reaching adolescence and adulthood. Many ASD characteristics require continuous support over a lifetime. As the ASD population ages, there is a growing need for resources to serve adolescents and adults with ASD.

Behavioral and Educational Interventions

There are many behavioral and educational approaches for individuals with ASD. The best known is Applied Behavior Analysis (ABA), which is well-supported by evidence. ABA focuses on systematically encouraging (and reinforcing) positive, functional behaviors, while reducing negative or nonfunctional ones, often by teaching a more appropriate replacement skill.

Many studies have shown that children who receive intensive early intervention services-especially those who receive at least two years of intensive intervention prior to entering elementary school-experience significant gains in functional communication, cognitive skills, and behavior and need fewer support services in school.

Developmental models are another common intervention approach. These models aim to meet the child at his or her development level and use the child's current strengths to build new skills. Relationship-based models often engage parents and focus on fostering genuine relationships and creating a desire and ability to live in a changing environment.  Many approaches now incorporate both ABA and developmental or "relationship-based" models.

See behavioral and educational resources [3].

Social Skills Interventions

There are many social skills interventions for individuals with ASD, but designing research to measure the effectiveness of these interventions is challenging and there is not much supporting research evidence. Social skills groups that include typically developing children have the most research support. A few examples of social skills strategies include:

• Social skills groups - individuals with ASD practice social skills with each other and/or other children on a regular basis.
• Social Stories^TM - teachers, therapists, clinicians, and caregivers use stories and drawings to build social understanding.
• Hidden Curriculum - teachers and clinicians directly point out "unspoken" social rules.
• Social scripts - teachers and clinicians give individuals with ASD "scripts" for common social situations.
• Computers and other technology - teachers and clinicians use videos, software, or virtual-reality programs to teach complex social skills, such as recognition of emotions in facial expressions and tone of voice.

Speech-Language Pathology

Individuals with ASD have challenges communicating with others. A certified speech-language pathologist may work on skills such as:

• Non-verbal communication - teaching communication through gestures, a picture exchange system (such as PECS), an electronic talking device, or another alternative or augmentative communication tool.
• Pragmatics - helping individuals understand when and how to use language socially.
• Conversation skills - practicing back-and-forth exchanges, such as turn-taking or joint attention.
• Concepts - helping individuals understand abstract concepts.

Occupational Therapy

Occupational therapists help individuals with ASD interact with the world around them. One aspect of occupational therapy is Sensory Integration, which allows the child to interact more effectively by addressing limitations he or she might have in processing information and integrating sensory information.

For example, an occupational therapist may help individuals with ASD by:

• Leading activities that help improve attention and awareness (when the individual is theorized to be "under-reactive") or reduce overall arousal (in the case of "hyper-arousal").
• Facilitating play that teaches and helps individuals with ASD to participate in communication with others.
• Teaching strategies to help transition from one place or activity to the next.
• Developing adaptive techniques and strategies to get around apparent disabilities (e.g., keyboarding or using a weighted pencil to facilitate handwriting).

Such sensory approaches try to help manage symptoms of ASD, which are highly complex and variable from patient to patient. Due to the complexity of both ASD and sensory-based approaches, the research base for these approaches is limited.

See occupational therapy resources [4].

Medications

Antipsychotic drugs: Some atypical antipsychotics are used to treat irritability and behavioral problems, such as aggression, self-injury, and rapid mood swings. Risperdone (RisperdalTM) which was approved by the FDA in 2006 for irritability (aggression, self-injury, temper tantrums, and rapid mood changes) in individuals with ASD, is the best studied. Recent studies suggest Risperidone may be associated with improved overall functioning and social responsiveness; however, it has associated side effects of weight-gain and adverse metabolic effects (increasing the potential risk of high cholesterol or diabetes).

Alpha-adrenergic agonists: Limited (and often very small) studies of Clonidine and Guanfacine report improvements in behaviors such as hyperactivity, impulsivity, stereotypies, self-stimulation, inappropriate speech, irritability, aggression, and oppositional behavior as a frequent side-effect in individuals with ASD.

Mood Stabilizers: These drugs (such as Divalproex sodium (Valproic Acid), Lamotrigine (Lamictal) or Topiramate (Topomax)) are most commonly used to treat seizures, bipolar disorder, and some behavioral symptoms. Some studies have started to assess behavior changes associated with these medications with mixed outcomes. Such medications are occasionally tried on a case-by-case basis.
Antidepressants: Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) have not been clearly beneficial for individuals with ASD and are sometimes associated with side effects. However, SSRIs are sometimes used to target specific symptoms such as aggression, self-injurious behavior, and anxiety.

Stimulants: Individuals with ASD often have significant problems with inattention, hyperactivity, and impulsivity. The Diagnostic and Statistical Manual (DSM) provides diagnosis criteria for both ASD and Attention Deficit Hyperactivity Disorder (ADHD).  Because DSM rules exclude adding an ADHS diagnosis when an ASD diagnosis has already been made, the prevalence of ADHD in children and youth with ASD is unknown.

Available research tells us that stimulants tend to produce highly variable responses in children with both ASD and ADHD symptoms. On average, the response in children with ASD may be less favorable than in typically developing children, and there may be a greater chance of side effects. This said, stimulants may still be a reasonable first therapeutic choice for previously untreated children with ASD and uncomplicated ADHD. As with any individual with ADHD, stimulant treatment should be implemented in increments using systematic monitoring for improvements and side effects (such as insomnia, abdominal pain, headache and loss of appetite).

Anticonvulsants: Individuals with ASD have a higher incidence of seizures and epilepsy compared to the general population and may require anticonvulsant medication to treat seizures.

Sleep Medications: Individuals with Autism have higher rates of sleep disturbance compared to the general population. Some medications used to treat sleep disturbances include: clonidine, trazodone, melatonin, and antihistamines. Studies have demonstrated that individuals with ASD may have abnormal production of melatonin, and preliminary studies have shown melatonin to be a safe and effective sleep aid in children with ASD. Interestingly, in an open-label study with 33 subjects, the restless sleep of children with ASD and iron deficiency improved with iron supplementation.

Gastrointestinal agents: While yet controversial and difficult to assess, many studies point to an increased incidence of gastrointestinal issues (such as chronic diarrhea, constipation, or acid reflux disease) in individuals with ASD. It is thought that reducing these symptoms may allow a child to gain maximum benefit from behavioral and educational therapies. Medications such as probiotics, ranitidine (Zantac), or famotidine (PepcidTM) may be prescribed for specific gastrointestinal conditions.

Probiotics have been shown to have a positive effect on diarrhea. While probiotics may improve gastrointestinal function (for example, decreasing diarrhea), studies have not evaluated whether probiotics are associated with core ASD symptoms (such as social interactions or communication). More than 12 well-designed randomized controlled research studies failed to demonstrate any effect of secretin, a gastrointestinal hormone, on ASD symptoms.

See medication resources [5].

What Are Some Integrative Therapies and Healing Practices Commonly Used in Individuals with ASD?

Vitamins/Minerals

Some experts and parents believe that children with ASD do not break down or process the nutrients they consume in expected ways. To address this, providers sometimes recommend a daily multi-vitamin, especially if the children:

• Have self-restricted diets
• Follow a specific diet (for example, if a child is consuming a diet free of casein, a multi-vitamin may be necessary to ensure adequate vitamin D and calcium intake.)
• Have chronic diarrhea, constipation, or gastrointestinal inflammation

The use of mega-dose vitamins and nutritional supplements beyond a multi-vitamin are not fully supported for routine use. Below is a list of some vitamins and supplements that have been recently studied regarding their use with individuals with ASD.

• Vitamin B6 and Magnesium (Mg) - Studies of B6 and Mg are limited and have conflicting results. Recent good quality research by Tolbert and Findling found that B6 and magnesium did not result in statistically significant effects. Hence the evidence is not adequate to make clinical recommendations. A recent study focusing on children with Asperger's Syndrome and PDD-NOS (Pervasive Developmental Disorder-Not Otherwise Specified), found that Vitamin B6 appeared to increase verbal IQ scores, but it showed no improvements in social functioning.
• Vitamin B12, Folinic Acid, Dimethylglycine (DMG), and Glutathione - Preliminary research suggests that individuals with ASD have impairments in methylation and sulfation, meaning that the cells do not receive the proper instructions to develop. The supplements listed above have shown some improvements in these cellular processes, per several research studies.
• Vitamins C, E, Selenium, and Glutathione - Oxidative stress (an increase in toxins, such as free radicals, and a decrease in the body's ability to detoxify or repair damages caused by these free radicals) has been shown to be elevated in individuals with ASD. Oxidative stress is significant because this renders the central nervous system exquisitely sensitive to free radical attack. The vitamins and supplements listed above have been used in an attempt to reduce oxidative stress. One double-blind, placebo-controlled study by Dolske showed a decrease in stereotypic behaviors after use of vitamin C, which was hypothesized to regulate dopamine. This study was small and has not been replicated.
• L-carnitine - It has been suggested by Lombardi that there is an increased prevalence of mitochondrial disorders (disorders affecting the mitochondria or "energy powerhouses" inside of cells) in individuals with ASD. Both mitochondrial disorders and ASD are complex disorders that are challenging to diagnose, making research difficult and the relationship unclear. While one case series by Filipek suggested that children with ASD may have low carnitine, treatments targeting mitochondrial function (such as L-carnitine) are not currently indicated as standard treatment for individuals with ASD.
• Amino Acids and Carnosine - Amino acids used as alternative treatments in ASD include taurine, lysine, or GABA, but they lack research. One by Chez found that L-carnosine improved participants' language and Autism symptoms on the Gilliam Autism Rating Scale and Receptive One-Word Picture Vocabulary Test.
• Vitamin A - Megson hypothesizes that vitamin A may be associated with ASD symptoms because it is necessary for functioning of the receptors critical for sensory perception, attention, and language processing. However, vitamin A for individuals with ASD has not been studied in clinical trials. Note that vitamin A in high doses has potential for toxicity.
• Vitamin D and Calcium - Milk products are a major source of vitamin D and calcium. Providers should evaluate vitamin D and calcium intake in individuals with ASD because: 1) many individuals with ASD consume a specific casein-free diet and 2) individuals with ASD may consume less dairy regardless of imposed dietary limitations. While there have been no controlled trials of vitamin D or Calcium related to Autism symptoms, some experts have suggested that vitamin D deficiency could be a contributing factor to ASD and to the higher rate of educational ASD services for children of Somali descent who are at higher risk for vitamin D deficiency.
• Zinc - It is hypothesized that individuals with ASD have an increased prevalence of abnormal zinc-copper balance and abnormal metallothionein function (metallothionein is a protein that binds to and is involved in zinc and copper regulation). However, there are no controlled trials involving zinc and Autism symptoms.
• Iron - Iron is necessary for normal neurodevelopment. A few studies, such as one by Dosman in 2006, suggest that children with ASD have a higher rate of iron deficiency compared to children without Autism. Dosman's 2007 study also suggested that iron deficiency in ASD is related to sleep disturbances. Although one clinical trial by Konofal suggested the iron supplements could have promising effects on ADHD symptoms, no clinical trials have tested the effects of iron supplementation on individuals with ASD.

See vitamin/mineral resources [6].

Essential Fatty Acids (Omega 3)

Research on Omega-3 fatty acids is preliminary but encouraging. These "essential" fatty influence various central nervous and immune system biochemical processes. Experts, such as Young and Richardson, also believe that Omega-3 fatty acids play a role in various neuropsychiatric or brain disorders. The current U.S. diet is thought to include too many Omega-6s and too few Omega-3s. Somewhat conflicting studies by Sliwinski and Vancassell have shown that children with Autism may have increased or decreased levels of Omega-3s compared to children without ASD.

Recent studies by Amminger, Bell, and Patrick have found that increasing Omega-3s in the diet is associated with improvements in people with ASD, particularly in hyperactivity and repetitive behaviors, as well as cognitive and motor skills, concentration, eye contact, sociability, and sleep. (And one study based on parental report suggested that infants who received essential fatty acid supplements in their breast milk or formula were less likely to develop ASD.)

See omega-3 resources [7].

Dietary Interventions

The food a person eats affects the body in many ways. Many children with ASD follow specific diets, often because caregivers report that dietary interventions correlate with improvements in behaviors or medical symptoms (such as reflux, diarrhea, abdominal pain, or eczema). Some commonly followed diets include:

• Casein-free diet - Casein is a protein found in milk; this diet eliminates milk and all by-products of milk.
• Gluten-free diet - Gluten is a protein found in many grains; this diet eliminates such grains.
• Feingold diet - Eliminates additives and chemicals.
• Specific carbohydrate diet - Removes specific carbohydrates, including all grains, lactose, and sucrose.
• Yeast-free diet - Eliminates yeast and sugar.

Kvinsberg's 2002 study suggested that a gluten-free casein-free (GFCF) diet in individuals with Autism reduces Autistic traits; other studies have found no significant difference. Larger randomized controlled trials of GFCF diets are currently underway. While no evidence-based studies have evaluated their efficacy, digestive enzymes are often used for the purpose of aiding in digestion of proteins such as gluten and casein. Families choosing to utilize a GFCF diet should ensure adequate nutrition with particular attention to protein, vitamin D, and calcium.

See dietary resources [8].

Mind-Body Approaches

Mind-body approaches [9] aim to support the body through various methods, including decreasing anxiety and self-regulation techniques. Some of the following examples are supported by preliminary studies but are all still considered experimental: yoga [10], music therapy [11], craniosacral massage [12], massage/therapeutic touch [13], aromatherapy [14], pet therapy (i.e. horses, dogs), and auditory integration.
 
See mind-body resources [15].

Other Alternative Therapies

Below are a couple of alternative therapies with limited supporting evidence that pose significant risks.

Immunological agents

The connection between the immune system and ASD is being studied. It has been reported that children with ASD are more likely to have infectious and allergy-related disorders, and many abnormalities have been reported related to the functioning of the immune system. Some immune system-altering medications used by children with ASD include: intravenous immunoglobulins (IVIG), anti-viral medications, anti-fungal medications, and steroids. IVIG is not FDA-approved for Autism, it is costly and may carry risks of headaches, anaphylactic shock, meningitis, or infectious disease. While one study by Sandler reported short-term behavioral improvements in 11 children taking vancomycin, further studies are not available.

It should be noted that while anti-infectives are frequently used in general medical practice for things such as ear infections, all come with potential side effects, such as rash, allergy, disruption of gastrointestinal flora, or liver damage. Long-term steroids carry many potential risks, including bone fractures, effects on height and metabolism, and immunosupression.

See immunological resources [16].

Hyperbaric oxygen therapy (HBOT)

The use of HBOT in individuals with ASD has been suggested for its ability to increase blood flow in the brain, reduce inflammation, and reduce oxidative stress. A preliminary multi-site randomized controlled trial by Rossingol revealed significant improvements in overall functioning, receptive language, social interaction, eye contact, and sensory/cognitive awareness after HBOT in individuals with Autism. However, a subsequent similar study by Granpeesheha did not find HBOT to be effective in multiple assessments. HBOT carries significant potential risks, including ear pain and oxygen toxicity, and it can be expensive. Further investigation is necessary to determine safety and efficacy. 

See HBOT resources [17].

Chelation

Some experts and partents theorize that individuals with ASD have less capacity to clear heavy metals or are more susceptible to the effects of heavy metals on immune function and the central nervous system. Chelation therapy involves the use of agents to remove heavy metals from the body. No controlled studies have evaluated the safety or efficacy of chelation in individuals with ASD. Chelation carries serious risks of vomiting, netropenia, and death. One death occurred in a child with Autism due to hypocalcemia (low serum calcium levels in the blood) resulting from the inappropriate use of EDTA (a chelator). Deaths attributed to chelation complications have also occurred in individuals without ASD.

See chelation resources [18].

How to Combine Integrative Therapies and Healing Practices in ASD

Central Place of Care or Health Home: It is critical to have a working relationship with a provider, or team of providers, who can help you navigate through the numerous therapies and treatments for ASD. At least one central provider or team should know all the therapies and treatments used by you or your child. The provider can be a conventional physician, nurse practitioner, therapist, or other professional who is philosophically aligned with your perspective on the disease.

Collect Data: People with ASD are unique individuals and may respond to treatments differently. It is important to monitor progress with a new treatment or therapy. Work with a professional to choose target behaviors or symptoms (i.e., improved eye contact, less diarrhea, etc.) and specific methods to rate these target behaviors (such as a 1-5 rating scale on a calendar). Collect data before and after you make the treatment change. Make only one change at a time. Consider not telling (blinding) one parent, a therapist, or teacher about the treatment and asking for their evaluation of the child. Work with a professional to review the data and evaluate whether the treatment correlates with improvements.

Consider External Factors: Recognize all the factors that could influence your treatment trial. Take natural child development into account and recognize that all children go through stages during which they gain new skills or may focus less on other skills previously acquired. Additionally, all people have "good days" and "bad days."  People are also influenced by their environment (i.e., a disrupted schedule due to the holidays, less sunlight in the wintertime, a new teacher, etc.). Recognize that these typical stages of development and "ups and downs" may correlate with a new treatment. Parents' feelings of anxiety or hope can also influence their perception of the "results" or their treatment of the child. Ensure that your treatment trial is long enough to account for these types of normal variation.

Educate Yourself: Learn all you can about treatments and, in addition to proposed benefits, be sure to inquire about potential risks, such as cost, time, or side effects. Use the same instincts you have developed as a consumer to make judgments about potential "hype." Ask about the evidence behind a treatment, realizing that while randomized controlled clinical trials are the highest level of evidence, they are challenging to conduct in individuals with ASD.

Resources

Websites

American Academy of Pediatrics (AAP) [19]

Autism Science Foundation [20]

Autism Speaks [21]

Interactive Autism Network (IAN) [22]

Autism Research Institute (ARI) [23]

Autism Treatment Network (ATN) [24]

Centers for Disease Control and Prevention (CDC) Autism Information Center [25]

Interagency Autism Coordinating Committee (IACC) [26]

Maternal and Child Health Bureau (MCHB) [27]

M.I.N.D. Institute (Medical Investigation of Neurodevelopmental Disorders) [28]

National Institute of Child Health and Human Development (NICHD)
[29]
Institute for Functional Medicine [30]

National Center for Complementary and Alternative Medicine (NCCAM) [31]

PedCAM Network [32]

General ASD Resources

Autism and Developmental Disabilities Monitoring Network Surveillance Year 2006 Principal Investigators, and Centers for Disease Control and Prevention. Prevalence of Autism Spectrum Disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. Morbidity and Mortality Weekly Report Surveillance Summaries. 2009;58(SS10):1-20.

Billstedt E, Gillberg IC, Gillberg C. Autism after Adolescence: Population-Based 13- to 22- Year Follow-up Study of 120 Individuals with Autism Diagnosed in Childhood. Journal of Autism and Developmental Disorders. 2005; 35(3):351-360.

Eaves LC, Ho HH. Young Adult Outcome of Autism Spectrum Disorders. Journal of Autism and Developmental Disorders. 2008;38:739-747.

Gillberg C, Steffenburg S. Outcome and Prognostic Factors in Infantile Autism and Similar Conditions: A Population-Based Study of 46 Cases Followed Through Puberty. Journal of Autism and Developmental Disorders. 1987;17(2):273-287.

Hertz-Picciotto, Irva; Delwiche, Lora, The Rise in Autism and the Role of Age at Diagnosis. Epidemiology: January 2009 - Volume 20 - Issue 1 - pp 84-90.

Howlin P, Goode S, Hutton J, Rutter M. Adult Outcome for Children with Autism. Journal of Child Psychology and Psychiatry. 2004;45(2):212-229.

Zecavati, N., MD, MPH, and Sarah J. Spence, MD, PhD (2009). Neurometabolic Disorders and Dysfunction in Autism Spectrum Disorders. Pediatric Neurology, 9:129-136.

Return to What Are Autism Spectrum Disorders? [33]

Behavioral & Educational Intervention Resources

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IVTR). Washington, DC: American Psychiatric Publishing; 2000.

Cohen, H., Amerine-Dickens, M., & Smith, T. (2006). Early intensive behavioral treatment: Replication of the UCLA model in a community setting. Developmental and Behavioral Pediatrics, 27(2), S145-S155.

Greenspan, S.I., & Wieder, S. (1997). Developmental patterns and outcomes in infants and children with disorders in relating and communicating: A chart review of 200 cases of children with autistic spectrum diagnoses. Journal of Developmental and Learning Disorders, 1, 87-141.

Horner, R.H., Carr, E.G., Strain, P.S., Todd, A.W., & Reed, H.K. (2002). Problem behavior interventions for young children with autism: A research synthesis. Journal of Autism and Developmental Disorders, 32(5), 423-446.

Howard, J.S., Sparkman, C.R., Cohen, H.G., Green, G., & Stanislaw, H. (2005). A comparison of intensive behavior analytic and eclectic treatments for young children with autism. Research in Developmental Disabilities, 26, 359-383.

Jensen, V.K., & Sinclair, L.V. (2002). Treatment of autism in young children: Behavioral intervention and applied behavior analysis. Infants and Young Children, 14(4), 42-52.

Reed, P., Osborne, L.A., & Corness, M. (2006). Brief report: Relative effectiveness of different home-based behavioral approaches to early teaching intervention. Journal of Autism and Developmental Disorders, epublished ahead of print December 19, 2006.

Sallows, G.O., & Graupner, T.D. (2005). Intensive behavioral treatment for children with autism: Four-year outcome and predictors. American Journal on Mental Retardation, 110(6), 417-438.

Schreibman, L. (2000). Intensive behavioral/psychoeducational treatments for autism: Research needs and future directions. Journal of Autism and Developmental Disorders, 30(5), 373-378.

Smith, T., Groen, A.D., & Wynn, J.W. (2000). Randomized trial of intensive early intervention for children with pervasive developmental disorder. American Journal on Mental Retardation, 105(4), 269-285.

Return to Behavioral & Education Interventions [34]

Occupational Therapy Resources

Scott M. Myers, MD, Chris Plauché Johnson, MD, Council on Children With Disabilities, Clinical Report, Management of Children with Autism Spectrum Disorders. Pediatrics Vol. 120 No. 5 November 2007, pp. 1162-1182.

Return to Occupational Therapy [35]

Medication Resources

Aman, M.G., PhD, Cristan A. Farmer,MAc,d, Jill Hollway, MAc,d, L. Eugene Arnold, Med, MD, Treatment of Inattention, Overactivity, and Impulsiveness in Autism Spectrum Disorders, Child Adolesc Psychiatric Clin N Am 17 (2008) 713-738.

Andersen IM, Kaczmarska J, McGrew SG, et. al. Melatonin for insomnia in children with autism spectrum disorders. J Chil Neurol 2008;23:482-5.

Belsito KM, Law PA, Kirk KS, et al. Lamotrigine therapy for autistic disorder: a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2001;31(2):175-81.

Cremonini F, Di Caro S, Nista EC, et al. Meta analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. AlimentPharmacol Ther. 2002;16:1461-1467.

Dosman CF, Jessica A. Brian, Irene E. Drmic, Ambikaipakan Senthilselvan, Mary M. Harford, Ryan W. Smith, Waseem Sharieff, Stanley H. Zlotkin, Harvey Moldofsky, S. Wendy Roberts, Children With Autism: Effect of Iron Supplementation on Sleep and Ferritin, Pediatr Neurol 36(3):152-8.

Fankhauser MP, Karumanchi VC, German ML, et al. A double-blind, placebo-controlled study of the efficacy of transdermal clonidine in autism. J Clin Psychiatry 1992;53(3):77-82.

Garstang J, Wallis M, Randomized controlled trial of melatonin for children with autistic spectrum disorders and sleep problems, Child Care Health Dev 32(5):585-9.

Handen, B.L., & Lubetsky, M. (2005). Pharmacotherapy in autism and related disorders. School Psychology Quarterly, 20(2), 155-171., agitation, overactivity, and some stereotypic behaviors in individuals with ASD.

Hellings JA, Weckbaugh M, Nickel EJ, et al. A double-blind, placebo-controlled study of valproate for aggression in youth with pervasive developmental disorders. J Child Adolesc Psychopharmacol 2005;15(4):682-92.

Huang JS, Bousvaros A, Lee JW, Diaz A, Davidson EJ. Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig Dis Sci. 2002;47:2625-2634

Jaselskis CA, Cook EH, Fletcher KE, et al. Clonidine treatment of hyperactive and impulsive children with autistic disorder. J Clin Psychopharmacol 1992;12:322-7.

Levy SE, Hyman SL. Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev 2005;11:131-42.

Mazzone L, Ruta L. Topiramate in children with autistic spectrum disorders. Brain Dev 2006;28(10):668.

Melke J, Goubran Botros H, Chaste P, et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry 2008;13:90-8.

Nagaraj, R., Singhi, P, & Mahli, P. (2006). Risperidone in children with autism: Randomized, placebo-controlled, double-blind study. Journal of Child Neurology, 21(6), 450-5.

Posey DJ, Aman MG, McCracken JT, et al. Positive effects of methylphenidate on inattention and hyperactivity in pervasive developmental disorders: an analysis of secondary measures. Biol Psychiatry 2007;61:538-44.

Posey DJ, Decker J, Sasher TM, et al. Guanfacine treatment of hyperactivity and inattention in autism: a retrospective analysis of 80 cases. J Child Adolesc Psychopharmacol 2004;14: 233-41.

Research Units on Pediatric Psychopharmacology Autism Network. A randomized, doubleblind, placebo-controlled, crossover trial of methylphenidate in children with hyperactivity associated with pervasive developmental disorders. Arch Gen Psychiatry 2005;62:1266-74.

Stigler KA, McDougle CJ, Pharmacotherapy of Irritability in Pervasive Developmental Disorders, Child Adolesc Psychiatric Clin N Am 17 (2008) 739-752.

Varley, C.K., MD; Jon McClellan, MD, Implications of Marked Weight Gain Associated With Atypical Antipsychotic Medications in Children and Adolescents, JAMA. 2009;302(16):1811-1812.

Williams KW, Wray JJ, Wheeler DM. Intravenous secretin for autism spectrum disorder. Cochrane Database Syst Rev 2005;3:CD003495.

Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders TF, Hagerman RJ, Goodlin-Jones BL., The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome, J Clin Sleep Med. 2009 Apr 15;5(2):145-50.

Return to Medications [36]

Vitamins & Mineral Supplements Resources

Bejerot S, Humble M. Increased occurrence of autism among Somali children--does vitamin D deficiency play a role?, Tidsskr Nor Laegeforen. 2008 Sep 11;128(17):1986-7. Swedish.

Bolman, W.M., & Richmond, J.A. (1999). A double-blind, placebo-controlled, crossover pilot trial of low dose dimethylglycine in patients with autistic disorder. Journal of Autism and Developmental Disorders, 29(3), 191-194.

Bonisch, E. (1968). Experiences with pyrithioxin in brain-damaged children with autistic syndrome [Erfahrungen mit Pyrithioxin bei hirngeschadigten Kindern autistichem Syndrom]. Praxis der Kinderpsychologie und Kinderpsychiatrie, 17(8), 308-310.

Cannell JJ, Autism and vitamin D., Med Hypotheses. 2008;70(4):750-9. Epub 2007 Oct 24.

Chauhan, A., & Chauhan, V. (2006). Oxidative stress in autism. Pathophysiology, 13(3), 171-181.

Chez MG, Buchanan CP, Aimonovitch MC, et al. Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol 2002;17:833-7.

Deshpande, C., Dhir, A., & Kulkarni, S.K. (2006). Antagonistic activity of ascorbic acid (vitamin C) on dopaminergic modulation: Apomorphine-induced stereotypic behavior in mice. Pharmacology, 77(1), 38-45.

Dolske, M.C., Spollen, J., McKay, S., Lancashire, E., & Tolbert, L. (1993). A preliminary trial of ascorbic acid as supplemental therapy for autism. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 17, 765-774.

Dosman CF, Brian JA, Drmic IE, Senthilselvan A, Harford MM, Smith RW, Sharieff W, Zlotkin SH, Moldofsky H, Roberts SW. Children with autism: effect of iron supplementation on sleep and ferritin. Pediatr Neurol. 2007 Mar;36(3):152-8.

Dosman CF, Drmic IE, Brian JA, Senthilselvan A, Harford M, Smith R, Roberts SW. Ferritin as an indicator of suspected iron deficiency in children with autism spectrum disorder: prevalence of low serum ferritin concentration. Dev Med Child Neurol. 2006 Dec;48(12):1008-9.

Filipek PA, Juranek J, Nguyen MT, et al. Relative carnitine deficiency in autism. J Autism Dev Disord 2004;34:615-23.

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Nye, C., & Brice, A. (2005). Combined vitamin B6-magnesium treatment in autism spectrum disorder (Review). Cochrane Database of Systematic Reviews, Issue 4.

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Tsao CY, Mendell JR. Autistic disorder in 2 children with mitochondrial disorders. J Child Neurol. 2007 Sep;22(9):1121-3.

Walsh W. Metallothionein and autism. Presented at: Defeat Autism Now Conference. San Diego (CA), October 3, 2003).

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Omega-3 Fatty Acids Resources

Amminger, G.P., Berger, G.E., Schafer, M.R., Klier, C., Friedrich, M.H., & Feucht M. (2007). Omega-3 fatty acids supplementation in children with autism: A double-blind randomized, placebo-controlled pilot study. Biological Psychiatry, 61, 551-553.

Bell, J.G., MacKinlay, E.E., Dick, J.R., MacDonald, D.J., Boyle, R.M., & Glen, A.C.A. (2004). Essential fatty acids and phospholipase A2 in autistic spectrum disorders. Prostaglandins, Luekotrienes and Essential Fatty Acids, 71, 201-204.

Patrick L, Salik R. The effect of essential fatty acid supplementation on language development and learning skills in autism and asperger's syndrome. Autism-Asperger's Digest 2005;36-7.

Richardson, A.J., & Ross, M.A. (2000). Fatty acid metabolism in neurodevelopmental disorder: a new perspective on associations between attention-deficit/hyperactivity disorder, dyslexia, dyspraxia, and the autistic spectrum. Prostaglandins, Leukotrienes and Essential Fatty Acids, 63(1/2), 1-9.

Sliwinski S, Croonenberghs J, Christophe A, et al. Polyunsaturated fatty acids: do they have a role in the pathophysiology of autism? Neuro Endocrinol Lett 2006;27:465-71.

Vancassel, S., Durand, G., Barthelemy, C., Lejeune, B., Martineau, J., Guilloteau, D., Andres, C., & Chalon, S. (2001). Plasma fatty acid levels in autistic children. Prostaglandins, Luekotrienes and Essential Fatty Acids, 65(1), 1-7.

Young, G., & Conquer, J. Omega-3 fatty acids and neuropsychiatric disorders. Reproduction, Nutrition, and Development, 45(1), 1-28.

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Dietary Interventions Resources

Brudnak MA, Rimland B, Kerry RE, et al. Enzyme-based therapy for autism spectrum disorders - is it worth another look? Med Hypotheses 2002;58:422-5.

Elder, J.H., Shankar, M., Shuster, J., Theriaque, D., Burns, S., & Sherrill, L. (2006). The gluten-free, casein-free diet in autism: Results of a preliminary double blind clinical trial. Journal of Autism and Developmental Disorders, 36(3), 413-420.

Hyman, S., Current Study: Diet and Behavior in Young Children With Autism, ClinicalTrials.gov identifier: NCT00090428, http://clinicaltrials.gov/ct2/show/NCT00090428 [40].

Jyonouchi H., Food allergy and autism spectrum disorders: is there a link? Curr Allergy Asthma Rep. 2009 May;9(3):194-201. Review.

Jyonouchi H, Sun S, Itokazu N. Innate immunity associated with inflammatory responses and cytokine production against common dietary proteins in patients with autism spectrum disorder. Neuropsychobiology 2002;46(2):76-84.

Jyonouchi H, Geng L, Ruby A, Zimmerman-Bier B. Dysregulated innate immune responses in young children with autism spectrum disorders: their relationship to gastrointestinal symptoms and dietary intervention, Neuropsychobiology. 2005;51(2):77-85.

Knivsberg, A.M., Reichelt, K.L., Hoien, T., & Nodland, M. (2002). A randomized, controlled study of dietary intervention in autistic syndromes. Nutritional Neuroscience, 5(4):251-261.

Lucarelli S, Frediani T, Zingoni AM, et al. Food allergy and infantile autism. Panminerva Med 1995;37(3):137-41.

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Immunological Agents Resources

Interactive Autism Network [42]

Sandler RH, Finegold SM, Bolte ER, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. J Child Neurol 2000;15:429-35.

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HBOT Resources

Daniel A. Rossignol, Lanier W. Rossignol, Hyperbaric oxygen therapy may improve symptoms in autistic children, Med Hypotheses. 2006;67(2):216-28. Epub 2006 Mar 22.

Granpeesheha, D. (2010). Randomized trial of hyperbaric oxygen therapy for children with autism. Research in Autism Spectrum Disorders, 4(2), 268-275.

Rossignol DA, Rossignol LW, James SJ, Melnyk S, Mumper E., The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study., BMC Pediatr. 2007.

Rossignol, D., Rossignol, L., Smith, S. et al. (2009). Hyperbaric treatment for children with autism: a multicenter, randomized, double-blind, controlled trial, BMC Pediatrics, 9:21.

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Chelation Resources

Brown MJ, Willis T, Omalu B, et al. Deaths resulting from hypocalcemia after administration of edentate disodium: 2003-2005. Pediatrics 2006;118:e534-6.

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Mind-Body Resources

American Academy of Pediatrics. Committee on children with disabilities: auditory integration training and facilitated communication for autism. Pediatrics 1998;102:431-3.

Downey PA, Barbano T, Kapur-Wadhwa R, et al. Craniosacral therapy [46]: the effects of cranial manipulation on intracranial pressure and cranial bone movement. J Orthop Sports Phys Ther 2006;36:845-53.

Gold C, Wigram T, Elefant C. Music therapy for autistic spectrum disorder. Cochrane Database Syst Rev 2006;2:CD004381.

Heaton P. Interval and contour processing in autism. J Autism Dev Disord 2005;35:787.

Kern P, Wolery M, Aldridge D. Use of songs to promote independence in morning greeting routines for young children with autism. J Autism Dev Disord 2007;37:1264-71.

Moran RW, Gibbons P. Intraexaminer and interexaminer reliability for palpation of the cranial rhythmic impulse at the head and sacrum. J Manipulative Physiol Ther 2001;24:183-90.

Silva LM, Cignolini A, Warren R, et al. Improvement in sensory impairment and social interaction in young children with autism following treatment with an original Qigong [47] massage methodology. Am J Chin Med 2007;35:393-406.

Sinha Y, Silove N, Wheeler D, et al. Auditory integration training and other sound therapies for autism spectrum disorders: a systematic review. Arch Dis Child 2006;91:1018-22.

Sinha Y, Silove N, Wheeler D, et al. Auditory integration training and other sound therapies for autism spectrum disorders. Cochrane Database Syst Rev 2004;(1) CD003681.

Whippell J. Music in intervention for children and adolescents with autism: a meta-analysis. J Music Ther 2004;41:90-106.

Williams TI. Evaluating effects of aromatherapy massage on sleep in children with autism: a pilot study. Evid Based Complement Alternat Med 2006;3:373-7.

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