Transcript Detoxification and Chelation: Caution, Caveats, and

How to Assess and Prioritize
Treatments: Using Evidence-Based
Medicine to Choose Effective
Treatments for Autism and ADHD
Dan Rossignol, MD FAAFP
International Child Development Resource Center
321-259-7111 www.icdrc.org
Autism One / Autism Canada 2009 Conference
October 31, 2009
Disclosures:
I have received funding for two studies on
hyperbaric treatment in children with autism
from the International Hyperbarics Association
but I have no commercial or financial
relationships with chamber manufacturers.
With all treatments and recommendations,
please consult with your child’s physician
before implementation.
The use of every treatment in individuals
with autism is “off-label” except for
risperidone for the treatment of irritability
Autism Spectrum
ADHD
Asperger
Syndrome
PDD-NOS
Autism
Psychologically / Behaviorally defined
Communication
Stereotypical
behaviors
Social
interaction
Underlying pathophysiology ???
Autism: Pathophysiology
 Cerebral hypoperfusion
 Inflammation
– Cerebral
– Gastrointestinal
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Dysbiosis
Mitochondrial dysfunction
Oxidative stress
Impaired glutathione production
Environmental toxicant exposures
Study Descriptive Terms
 Prospective: planned ahead of time
 Randomized: participants assigned to a
group by random allotment
 Double-blind: Neither participants nor
researchers know group assignment
 Placebo-controlled: A placebo is given
to one group of participants
 Cross-over: placebo group crosses
over and gets treatment
Placebo Effect
 As high as 30-37% in several studies in
children with autism
 Points to need for double-blind,
placebo-controlled studies
 However, also need to treat children
now, and cannot always wait for these
types of study
 Need to evaluate the risk/benefit ratio
of each treatment
Evidence-based Medicine:
Strength of Evidence (Efficacy)
 A: Supported by at least 2 prospective
randomized controlled trials (RCTs) or 1
systematic review
 B: Supported by at least 1 prospective RCT or
2 nonrandomized controlled trials
 C: Supported by at least 1 nonrandomized
controlled trial or 2 case series
 D: Troublingly inconsistent or inconclusive
studies or studies reporting no improvements
Caveat
 Double-blind, placebo-controlled studies
can cause you to lose sight of the
individual patient
– e.g., DMG: 2 negative double-blind placebocontrolled studies in autism (however, dose
in studies lower than we typically use). DMG
is ranked #17 by parents on ARI list. Some
children manifest good improvements with
DMG, including speech.
– e.g., Secretin
Caveat
Over 50% of what is done in medicine is “off-label”
http://clinicalevidence.bmj.com/ceweb/about/knowledge.jsp
Example of Study: A in Autism
 Melatonin: 2 randomized, double-blind,
placebo-controlled studies
demonstrating improvement in the
amount of time to fall asleep, number of
nighttime awakenings, and length of
sleep compared to both baseline and to
placebo.
Garstang and Wallis, 2006 Child Care Health Dev 32(5):585-9
Goodlin-Jones et al., 2009 J Clin Sleep Med 5:145-150
Garstang and Wallis, 2006 Child Care Health Dev 32(5):585-9
STEPS
 Safety: has it been studied in children?
 Tolerability: what are the side effects?
 Efficacy: does it work?
 Price: how much will it cost?
 Simplicity: how easy is it to do?
STEPS: Melatonin
 Safety: two double-blind studies
showing safety in children with autism
 Tolerability: very little side effects
 Efficacy: Double-blind studies showing
improvements compared to placebo
 Price: less than $30 per month
 Simplicity: pill taken at bedtime
DOEs versus POEMs
 DOE: Disease Oriented Evidence
– Example: Cholesterol pill lowers my
cholesterol by 50 points
– Example: Flecainide
– Example: MB12 increases glutathione
 POEM: Patient Oriented Evidence that
Matters
– Example: Cholesterol pill makes me live
longer, or prevents a heart attack or stroke
– Example: MB12 improves speech
Ideal Treatment
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Backed by Strength of Evidence: A
Safe
Tolerable
Efficacious
Cheap
Simple, in-home treatment
POEM: Outcome matters to child/parent
Treatment Options: Know
Your Reason for Treatment
 Based upon symptoms
– e.g., inattention: pycnogenol, zinc,
carnitine, iron, omega-3 fatty acids
 Based upon laboratory testing
– e.g., oxidative stress: pycnogenol,
carnitine, CoQ10
 Based upon probabilities
– e.g., most children with autism have low
glutathione: MB12, folinic acid, pycnogenol
Modified CGI – Parental
Autism Research Institute
Active
Treatment
Maintenance
IV Chelation
IVIG
Chelation
Anti-inflammatories
HBOT
Supplements
GFCF diet
Methyl B12
Antioxidants
McCracken et al., 2002 N Engl J Med 347(5):314-21
ABA Therapy
25/7
Eikeseth et al., 2007 Behav Mod 31(3):265-78
20/6
Rossignol, 2009 Annals Clin Psych, in press
Medications
 A: Acetylcholinesterase inhibitors
– rivastigmine, donepezil, galantamine
 B: Alpha-2 adrenergic agonists
– Clonidine, guanfacine
 B: Anti-inflammatory medications
– Spironolactone, pioglitazone, minocycline,
IVIG, ACTH, prednisone, pentoxifylline
 C: Glutamate antagonists
– Amantadine, memantine, lamotrigine
Overall Autistic Behavior
 A: Acetylcholinesterase inhibitors,
music therapy
 B: Alpha-2 adrenergic agonists, HBOT,
vision therapy
 C: Carnosine, piracetam, B6/Mg, GFCF
diet, cyproheptadine
Speech/Communication
 A: Acetylcholinesterase inhibitors,
music therapy
 B: Carnitine, Tetrahydrobiopterin (BH4),
Alpha-2 adrenergic agonists, HBOT
 C: Carnosine, B6/Mg, Omega-3 fatty
acids, piracetam, GFCF diet,
Cyproheptadine, Famotidine, Glutamate
antagonists, Auditory Integration
Therapy, Neurofeedback
Stereotypy
 A: Naltrexone
 B: Vitamin C, alpha-2 adrenergic
agonists
 C: Omega-3 fatty acids, B6/Mg,
cyproheptadine, famotidine, glutamate
antagonist, auditory integration
training, massage
Social Interaction
 A: Acetylcholinesterase inhibitors,
naltrexone
 B: Carnitine, tetrahydrobiopterin,
HBOT, oxytocin
 C: Carnosine, B6/Mg, GFCF diet,
Famotidine, Glutamate antagonists,
massage, neurofeedback
Attention/Concentration
 A: Omega-3 fatty acids (ADHD),
Pycnogenol (ADHD), zinc (ADHD),
acetylcholinesterase inhibitors,
nicotine, music therapy
 B: Carnitine, zinc, alpha-2 adrenergic
agonists
 C: Omega-3 fatty acids, glutamate
antagonists, Iron (if deficient, ferritin <
30), phosphytidylserine
Hyperactivity
 A: Eliminate food coloring, additives
and dyes; acetylcholinesterase
inhibitors, naltrexone
 B: Carnitine, alpha-2 adrenergic
agonists
 C: Omega-3 fatty acids, magnesium,
chelation, glutamate antagonists, AIT,
massage
Sleep
 A: Melatonin
 B: Carnitine, alpha-2 adrenergic
agonists
 C: Multivitamin, Omega-3 fatty acids
 D: Iron, 5-HTP
Irritability/Aggression
 A: Risperidone, Acetylcholinesterase
inhibitors, naltrexone (esp. self-injury)
 B: Alpha-2 adrenergic agonists, antiinflammatory medications
 C: Glutamate antagonists, auditory
integration therapy
Eye contact
 A: Acetylcholinesterase inhibitors,
music therapy
 B: Tetrahydrobiopterin, HBOT
 C: Omega-3 fatty acids, famotidine
Coordination
 A: Pycnogenol
 B: Carnitine, Vision therapy
 C: Omega-3 fatty acids
Toe-walking
 Tryptophan deficiency (5-HTP or TP)
 GI-related
Supplements with
Antiseizure Activity
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Taurine
Vitamin B6 / P5P
Magnesium
Omega-3 fatty acids
GABA
DMG
L-Carnosine
Rossignol, 2009 Annals Clin Psych, in press
Rossignol, 2009 Annals Clin Psych, in press
Rossignol, 2009 Annals Clin Psych, in press
Rossignol, 2009 Annals Clin Psych, in press
Rossignol, 2009 Annals Clin Psych, in press
Rossignol, 2009 Annals Clin Psych, in press
Typical Supplement Doses
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Vitamin C: 100 mg/kg/day
CoEnzyme Q 10: 5-10 mg/kg/day
Acetyl-L-Carnitine: 50-100 mg/kg/day
L-Carnosine: 200-400 mg twice a day
Pycnogenol: 1 mg/kg/day (often higher)
MB12 injections: 75 mcg/kg every 1-3 days
Folinic acid 400 mcg twice a day
Omega-3’s: DHA and EPA ~800 mg/day each
Zinc 20-150 mg/day
Melatonin: 1-6 mg 30 mins before bedtime
Typical Med Doses: Use Only
Under Physician Supervision
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Clonidine 0.1-0.2 mg at bedtime
Guanfacine 0.25-1 mg 3 times a day
Donepezil 2.5-5 mg at bedtime
Galantamine 2-8 mg twice a day
Spironolactone 1-3 mg/kg/day
Pioglitazone 15-30 mg/day
Memantine 5-10 mg bid
Lamotrigine 3-5 mg/kg/day
Summary: Where to start?
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Sleep / Melatonin / 5-HTP
Multivitamin
Omega-3 fatty acids
Anti-oxidants
Methyl B12 (SC injections)
Diet, at least organic and eliminate food
colorings and preservatives, GFCF
 Digestive enzymes / probiotics