THOMAS CHALLMAN
Transcription
THOMAS CHALLMAN
02/01/2016 C o m p l e m e n t a r y - A l t e r n a t i ve M e d i c i n e a n d A u t i s m : W h a t ’s t h e E v i d e n c e ? “Every complex problem has a solution that is simple, direct, plausible, and wrong.” Thomas Challman, MD Medical Director Geisinger Autism & Developmental Medicine Institute H.L. Mencken “ The less the evidence on which an opinion is based, the firmer the conviction with which it will be maintained.” • “We have perhaps the greatest find in the whole earth at this time. It is located on Native American land in western America. It is loaded with minerals, amino acids, vitamins and DNA material.” Leon Eisenberg |1 Geisinger Autism & Developmental Medicine Institute A Real Case Two brothers with autism Saw Doctor “X” who recommended the following: – Transdermal DMPS (dimercaptopropanesulfonate) drops, to remove ‘toxic heavy metals’ ($160/ounce) – A product called ‘Advanced Cell Life’ – Avoiding all future vaccines “… anti-tumor, anti-viral, anti-bacterial and antiparasitical. They both repair the DNA, Detox and rebuild the liver… Also contains latent solar energy hidden deep within its complex molecular structure … High quality Fulvic acid does an amazing job at repairing the DNA and re-connecting the DNA to all cells.” 1 02/01/2016 Management of Children with Autism Spectrum Disorders Educational and Behavioral Interventions – Preschool and School Programs – Specific Strategies • Intensive behavior therapy - ABA • Structured teaching • Speech and language therapy NCCAM classification of Complementary and Alternative Medicine (CAM) Mind-body medicine Manipulative and body-based practices Energy medicine Biologically-based practices Alternative medical systems – Augmentative and alternative communication • Occupational therapy, physical therapy • Social skills instruction Management of Children with Autism Spectrum Disorders Medication Management – Challenging behaviors – Seizures – Gastrointestinal Problems – Sleep Disturbance NCCAM classification of Complementary and Alternative Medicine (CAM) Mind-body medicine Manipulative and body-based practices Energy medicine Biologically-based practices Alternative medical systems The use of therapies considered CAM is common among adults and children NHIS (2002): 62% of adults used CAM in the previous year A majority of patients in these surveys did not discuss their use of these interventions with their regular medical provider 2 02/01/2016 Prevalence of CAM Use In pediatric populations, there is considerable variation in estimates of CAM use Selected pediatric outpatient and inpatient populations: 11-53% CAM use in autism (Levy, et al. 2003): 284 children recently diagnosed with an autism spectrum disorder • 30% were using some form of CAM • Vitamins, GI medications, melatonin • Gluten-free/casein-free diet, secretin • Cod liver oil, anti-infectives, chelation • Non-biological therapies Prevalence of CAM Use CAM use is common among children with chronic health conditions: • Cancer, arthritis, inflammatory bowel disease, asthma • ADHD, cerebral palsy, spina bifida, Down syndrome • Autism CAM use in autism (Levy, et al. 2003): 284 children recently diagnosed with an autism spectrum disorder • 16.9% were using a “biological” therapy • 9% were using a potentially harmful therapy Prevalence of CAM Use CAM use in autism (Green, et al. 2006): • • • • • • Internet survey of 552 caregivers Alternative diets: 26.8% Vitamin supplements: 42.6% Detoxification (including chelation): 8.9% Other alternative therapies: 25.9% Mean number of interventions per child (standard + nonstandard): 7 Prevalence of CAM Use CAM use in autism (Hanson, et al. 2007): • • • • • Survey of 112 families Biologically based practices: 54% Mind-body interventions: 30% Manipulation/body-based practices: 25% Energy therapies: 8% 3 02/01/2016 Prevalence of CAM Use CAM use in a large pediatric autism sample (Perrin, et al. 2012): 3173 individuals with ASD • Any CAM use: 28% • Special diets: 17% • Other CAM: 20% • Children with GI symptoms, seizures, or behavior problems had higher CAM use Pediatrics, November 2012,Vol 130, Suppl 2 Some of what is going on - from one website: Transdermal Secretin Oral Secretin Vitamin B-12 Intramuscular or Intravenous Magnesium Gluten and Casein Free Diets Pancreatic Enzymes Super Nu Thera Omega-3 Fatty Acids Prevalence of CAM Use Akins, et al (2014): • • • • Survey of 578 children with ASD 39% used some form of CAM 8.6% used an invasive, disproven or unsafe CAM therapy Higher parental education was associated with higher rates of CAM use J Dev Behav Pediatr, 2014, 35:1-10 Aloe Vera Flower of Sulphur Efalex Oil or DHA Oil Hyperbaric Oxygen Treatments Fibroblast Growth Factor 2 Live Cell and Stem Cell Therapy Anti-fungal Treatment Antibiotic Therapy 4 02/01/2016 Why Do People Use CAM? Naltrexone IV Immunoglobulin Therapy Detoxification for Heavy Metals EEG Bio-feedback Somatic therapies Craniosacral Therapy Traditional Chinese medicine Immunotherapy Why Do People Use CAM? Adults who use CAM are generally not dissatisfied with conventional medicine • CAM therapies may be more congruent with their specific values and life philosophies (Astin, 1998; Eisenberg, et al., 2001) Pediatrics: • Higher parental education • Higher rates of parental CAM use Birdee GS, et al.: Factors Associated With Pediatric Use of Complementary and Alternative Medicine (Pediatrics Vol. 125 No. 2 February 1, 2010, pp. 249 256) • Pediatric CAM users were more likely to take prescription medications, have a parent who used CAM, and have chronic conditions (anxiety or stress, musculoskeletal conditions, dermatologic conditions, or sinusitis) Why Do People Use CAM? Hall SE, Riccio CA: Complementary and alternative treatment use for autism spectrum disorders (Complementary Therapies in Clinical Practice, 2012, 18:159-163) • Four factors emerged as influencing decisions to use CAM: severity, child acceptance of the treatment, marital status, and educational level • Research support for the therapy did not emerge as contributing to variance for CAM use Why Do People Use CAM? In developmental disorders, non-standard interventions are often pursued based unsupported theories regarding the cause(s) of the disorder • Mercury chelation • “Leaky gut” GF/CF diet • Yeast “overgrowth” antifungals “It is a capital mistake to theorize before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts.” Sherlock Holmes, in Arthur Conan Doyle’s A Scandal in Bohemia “Cottingley Fairies” 5 02/01/2016 What Does the Evidence Show? Research into CAM Effectiveness of CAM in children 1999: creation of the National Center for Complementary and Alternative Medicine (NCCAM) The evidence-base for complementary medicine in children: a critical overview of systematic reviews Total NIH expenditure on research into CAM therapies since 1999: >$3 billion Hunt K, Ernst E. Arch Dis Child 2011;96:769–776. Source: http://nccam.nih.gov/ National Center for Complementary and Alternative Medicine: Stated mission: investigate complementary and alternative practices using the methods of rigorous science, train CAM researchers, and disseminate authoritative information regarding CAM to the public and professionals What Does the Evidence Show? “Study results are mixed on whether echinacea effectively treats colds or flu. For example, two NCCAM-funded studies did not find a benefit from echinacea…. Overview of 17 systematic reviews – Acupuncture, chiropractic, herbal medicine, homeopathy, hypnotherapy, massage and yoga – Results were unconvincing for most conditions – Acupuncture may be effective for postoperative nausea and vomiting – Hypnotherapy may be effective in reducing procedure-related pain However, other studies have shown that echinacea may be beneficial in treating upper respiratory infections.” 34 6 02/01/2016 CAM therapies in autism Summarized in “Complementary and Alternative Medicine Treatments for Children with Autism Spectrum Disorders”, Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 CAM therapies in autism Therapies with evidence ratings of >=B Efficacious Melatonin Vitamin C Transcranial magnetic stimulation Music therapy Non-efficacious Auditory integration Acupuncture Hyperbaric oxygen therapy Gluten-free, casein-free diet Secretin 7 02/01/2016 Melatonin Wright B, et al. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behaviour management strategies: a randomised controlled crossover trial. Journal of Autism and Developmental Disorders. Feb 2011 v41 i2 p175(10). Twenty-two children with autism spectrum disorders with severe dysomnias Double blind, randomized, controlled crossover trial Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 Melatonin Several studies have shown that average night sleep duration was longer on melatonin, and sleep-onset latency was shorter (by about 30 minutes) Melatonin Melatonin significantly improved sleep latency (by an average of 47 min) and total sleep (by an average of 52 min) compared to placebo, but not number of night wakenings The side effect profile was low and not significantly different between the two arms Levy SE and Hyman SL. Child Adolesc Psychiatric Clin N Am, 2015, 24:117-143 8 02/01/2016 Melatonin Appleton RE, et al. The use of melatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study. Health Technology Assessment (Winchester, England). 16(40):i-239, 2012. Randomised, double-blind, placebo-controlled, parallel study. Starting dose was 0.5 mg; the dose could be escalated to 12 mg Melatonin 146 children were randomized; 110 contributed data for the primary outcome Children treated with melatonin slept, on average, 23 minutes longer than those in the placebo group Melatonin reduced sleep onset latency by a mean of 45 minutes Melatonin Wirojanan J, et al. The efficacy of melatonin for sleep problems in children with autism, Fragile X syndrome, or autism and Fragile X syndrome. Journal of Clinical Sleep Medicine. 5(2):145-50, 2009 Apr 15. 4-week, randomized, DBPC, crossover design Melatonin dose: 3 mg Mean night sleep duration was longer on melatonin than placebo by 21 minutes (p = .02) Mean sleep-onset latency was shorter by 28 minutes (p = .0001) Omega-3 Fatty Acids “…there is currently insufficient scientific evidence to determine if omega-3 fatty acids are safe or effective for ASD.” Bent S, et al. Journal of Autism and Developmental Disorders. August 2009 v39 i8 p1145(10) Omega-3 Fatty Acids “To date there is no high quality evidence that omega-3 fatty acids supplementation is effective for improving core and associated symptoms of ASD.” James S, Montgomery P, Williams K. Omega-3 fatty acids supplementation for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews. (11):CD007992, 2011. Amminger, et al. (Biological Psychiatry, 2007) “We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy…. The results of this study provide preliminary evidence that omega-3 fatty acids may be an effective treatment for children with autism.” Or does it ? 9 02/01/2016 Table 1. Mean Scores on the Aberrant Behavior Checklist at Baseline and 6 Weeks Fish Oil The study referenced: “A Pilot Randomized Controlled Trial of Omega-3 Fatty Acids for Autism Spectrum Disorder” Bent, et al, J Autism Dev Disord, 2011, 41:545-554 Placebo Baseline 6 wks Baseline 6 wks Stereotypy 14.4 13.0 7.8 8.8 Hyperactivity 33.3 29.3 24.6 27.6 Table 1. Mean Scores on the Aberrant Behavior Checklist at Baseline and 6 Weeks Fish Oil Placebo Baseline 6 wks Baseline 6 wks Stereotypy 14.4 13.0 7.8 8.8 Hyperactivity 33.3 29.3 24.6 27.6 • Double-blind, placebo-controlled trial • No statistically significant benefit was observed in the treatment group Omega-3 Fatty Acids “Internet-based, Randomized, Controlled Trial of Omega3 Fatty Acids for Hyperactivity in Autism”, Bent et al, JAACAP, 2014, 53:658-666 • No statistically-significant improvement in hyperactivity in the treatment group 10 02/01/2016 Omega-3 Fatty Acids Vitamin B-12 “Dietary Docosahexaenoic Acid Supplementation in Children with Autism”, Voigt et al, JPGN, 2014, 58:715-722 • Dietary DHA supplementation of 200 mg/day did not improve the core symptoms of autism No convincing evidence of efficacy in the treatment of ASD Special diets Highly Implausible Therapies Gluten-free, casein-free diet Several small published controlled studies “Energy” Therapies Therapeutic touch Accupuncture Bertoglio, et al (J Altern Complement Med, 2010, 16:555-560) • 12 week, DBPC trial of methyl B-12 • No significant behavioral differences were found between the B-12 and placebo groups “Energy” healing Homeopathy Remember: There is no alternative physics. “…evidence for efficacy of these diets is poor.” Millward C, Ferriter M, Calver SJ, Connell-Jones GG. Gluten- and casein-free diets for autistic spectrum disorder. Cochrane Database of Systematic Reviews 2008, Issue 2 | 66 11 02/01/2016 Placebo/Expectancy Effects Placebo effect: “a genuine psychological or physiological effect, which is attributable to receiving a substance or undergoing a procedure, but which is not due to the inherent powers of that substance or procedure” (Stewart-Williams & Podd, 2004) Placebo/Expectancy Effects In studies of the medical treatment of depression, response rate to placebo is as high as 50% Placebo/Expectancy Effects Placebo/expectancy effects have major implications for the interpretation of improvement observed in the use of nonstandard therapies in children with developmental disorders Highlights the necessity of well-designed clinical trials to test specific interventions Does Evidence Matter? It should – but people often don’t care about evidence. Why? Sandler, et al. (1999): Trial of secretin in autism • Nearly 70% percent of the parents of the children in secretin study wanted to continue secretin treatment for their children, even after they knew the study showed that the secretin was ineffective Bronislaw Malinowski: Magic, Science, and Religion: and other essays (1954) • Anthropological study of Trobriand Islanders Risperidone in ADHD (Armenteros, et al. JAACAP, 2007) – 77% response rate in the placebo group 12 02/01/2016 Environmental conditions that result in increased danger or uncertainty lead to an increase in magical thinking Attention should therefore be directed toward interventions that reduce caregiver anxiety and uncertainty Appropriate psychosocial supports Education about what is truly known regarding the etiology, potential outcomes, and best treatments In developmental disorders, causes can be obscure and outcomes uncertain Caregiver stress is often high This contributes to an environment in which caregivers are susceptible to the development of idiosyncratic beliefs concerning etiologies and treatments Counseling Families about Nonstandard Treatments AAP (2001, reaffirmed 2010): – Seek information and share it with families – Evaluate the scientific merits of specific therapeutic approaches – Identify risks or potential harmful effects – Educate families to evaluate information about treatment options 13 02/01/2016 What’s the harm? Tolerance for risk is contingent upon the effectiveness of a therapy for a particular condition, and the severity of that condition Studies of CAM therapies rarely measure or report adverse effects Adverse effects should be viewed broadly Children seen by naturopathy and chiropractic practitioners: – are significantly less likely to receive the full complement of recommended vaccines – are significantly more likely to be diagnosed with a vaccine-preventable disease 1. Downey L, et al. Matern Child Health J 2010;14:922–30. 6. Twelve questions that can help identify questionable therapies (adapted from Nickel, 1996, and Lilienfeld, Lynn, and Lohr, 2003): 2. 3. 4. 5. Is the treatment based on a theory that is overly simplistic? Is the treatment based on proposed forces or principles that are inconsistent with accumulated knowledge from other scientific disciplines? Has the treatment changed little over a very long period of time? Is it possible to test the treatment claim? Have well-designed studies of the treatment been published in the peer-reviewed medical literature? Do proponents of the treatment “cherry pick” data that supports the value of the treatment, while ignoring contradictory evidence? 7. Do proponents of the treatment assume a treatment is effective until there is sufficient evidence to the contrary? 8. Do proponents claim that a particular treatment cannot be studied in isolation, but only in combination with a package of other interventions or practices? 9. Is the treatment promoted as being “natural” or free of adverse effects? 10. Is the treatment promoted primarily through the use of anecdotes? 11. Is scientific-sounding, but nonsensical, terminology used to promote the treatment? 12. Is the treatment promoted for widely diverse conditions? 14 02/01/2016 Changes You May Wish to Make in Practice 1. Ask parents about CAM use 2. Learn what types of non-standard therapies are most commonly used in your area 3. Talk to your families about the scientific plausibility of, and evidence for/against, specific types of CAM 4. Promote critical thinking skills among caregivers, therapists, trainees 5. Help give the families of your patients the tools they need to be able to evaluate evidence “It is largely up to physicians to steer parents away from these risky, ineffective, untested practices. It is the physician’s responsibility to encourage families to seek safe effective, evidence-based interventions.” Alison Singer and Ramita Ravi AMA Journal of Ethics April, 2015,Vol 17 No.4: 375-380 Additional References “Uncritically accepting every proffered notion, idea, and hypothesis is tantamount to knowing nothing…. Some ideas really are better than others.” Carl Sagan Challman TD, Myers SM (2011). Complementary and alternative medicine in developmental and behavioral pediatrics. In: Voigt RG, Macias MM, Myers SM, eds. Developmental and Behavioral Pediatrics. Elk Grove Village, IL: American Academy of Pediatrics. Lilienfeld, S. O., Lynn, S. J., & Lohr, J. M. (Eds.). Science and Pseudoscience in Clinical Psychology. Guilford Press: (2003) Additional References Association for Science in Autism Treatment: www.asatonline.com My e-mail: [email protected] Autism Science Foundation: www.autismsciencefoundation.org AAP: www.aap.org/healthtopics/autism.cfm 15