Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

ADHD - Diagnoses, Epidemiology & Precision Treatment - IMMH 2014


Published on

In his fourth and concluding lecture of the IMMH Conference in San Antonio, 2014, Dr. Cady reviews the statistics, epidemiology, biological nature and pharmacologic treatment of ADHD. The first part of the presentation was absolutely conventional allopathic psychiatry, inclusive of brain imaging.

The second part of the presentation considered: "If we are thinking about biological, psychological, and behavioral interventions for a 'psychiatric' patient, shouldn't we be considering the TWO biological levels?" The most normal biological level that "biologically trained psychiatrists" consider is medications and medication effectiveness. However, sometimes even the most vigorous, precise, and heroic efforts do not work. The potential confound it the underlying physiological, hormonal, nutrient, antioxidant, PUFA-rich state associated with optimal health and well being.

In the final analysis, shouldn't we make sure that we have BOTH of these biological foundations right?

We hope that you enjoy this provocative slide presentation.

Published in: Health & Medicine
  • Memory Improvement: How To Improve Your Memory In Just 30 Days, click here.. ★★★
    Are you sure you want to  Yes  No
    Your message goes here
  • Boost your brainpower with brain pill! find out more... ▲▲▲
    Are you sure you want to  Yes  No
    Your message goes here
  • For years, I was plagued by chronic yeast infections, including but not limited to: rashes, weight gain, insomnia, acne, constipation, chronic fatigue, depression, sensitivity to chemicals, you name it. After following your program, I had made a significant progress. My thrush, acne and rashes had vanished. My skin had almost completely cleared up. I hadn�t looked that good in 15 years. I felt rejuvenated, energized, happier and so much healthier... ▲▲▲
    Are you sure you want to  Yes  No
    Your message goes here
  • The 3 Secrets To Your Bulimia Recovery ◆◆◆
    Are you sure you want to  Yes  No
    Your message goes here
  • The Bulimia Recovery Program, We Recovered, You CAN TOO! ◆◆◆
    Are you sure you want to  Yes  No
    Your message goes here

ADHD - Diagnoses, Epidemiology & Precision Treatment - IMMH 2014

  1. 1. New Concepts in the Epidemiology, Diagnosis and Precision Treatment of ADHD in Children, Adolescents, and Adults Louis B. Cady, MD, FAPA, CEO & Founder – CCaaddyy WWeellllnneessss IInnssttiittuuttee Adjunct Clinical Lecturer – Indiana University School of Medicine Department of Psychiatry Child, Adolescent, Adult & Functional Neuropsychiatry – Evansville, Indiana IMMH 5th Annual Conference San Antonio, TX Sunday, Sept. 21
  2. 2. Continuing Medical Education Commercial Disclosure Requirement I, Louis B. Cady, M.D., have the following commercial relationships to disclose: • Speaker faculties: Forest Pharmaceuticals, Sunovion, Shionogi, Takeda-Lundbeck •Testing laboratories: Immunolaboratories, Great Plains Diagnostic Labs, LABRIX •Commercial endeavors: Pharmanex distributor •Historical honoraria, speaking: Bristol-Myers Squibb, Celltech, Cephalon, Eli Lilly, Glaxo Smith Kline, Janssen, McNeil, Pfizer-Roerig, Sanofi~aventis, Searle, Sepracor, Shire, Takeda, WorldLink Medical, Wyeth-Ayerst
  3. 3. This is where to follow along on your tablets and smart phones, or access the presentation slides later…
  4. 4. Prevalence: how much, and “why so much”?
  5. 5. Increased methylphenidate usage for attention deficit disorder in the 1990’s. Safer DJ et al. Pediatrics. 1996 Dec; 98(6 Pt 1):1084-8} • 2.5 X increase in MPH tx between 1990 and 1995 – 2.8% (1.5 million) US youths aged 5-18 received this medication in mid-1995 • “The increase in methylphenidate…appears largely related to – an increased duration of treatment; – More girls, adolescents and inattentive youths on the medication – And a recent improved public image of medication treatment.”
  6. 6. Prevalence data of parent report of ADHD “CURRENT Dx” by provider 2007 2011 IL 4.8% 7.2% IN 9.3% 13.0% KY 10.2% 14.8% Rates of ADHD diagnosis increased an average of 3% per year from 1997 to 2006 (CDC Vital & Health Statistics) accessed 01 26 2014
  7. 7. ADHD Stats at 3- 17 years of age. • 5 million children (9% for this age group) – Boys 12% – Girls 5% • Children with fair/poor health status 2½ X more likely to have dx. (8% vs 21%)
  8. 8. - Reviving American Maannuuffaaccttuurriinngg,, aacccceesssseedd 11 2277 22001144
  9. 9. aacccceesssseedd 0011 2277 22001144
  10. 10. Unemployment, underemployment are contemporary problems…
  11. 11. Genetic tendencies in ADHD
  12. 12. Faraone SV et al. Biol Psychiatry 2005 June 1;57(11):1313- 1323. Graphic from CNS Spectr. 2007;12:4 (Suppl 6): 6- 7
  13. 13. Genetic etiologies • Genes most commonly associated with ADHD involve dopamine. – Faraone SV, Perlis RH, Doyle AE, et al. Molecular genetics of attention-deficit/ hyperactivity disorder. Biol Psychiatry. 2005;57:1313-1323. • PET studies show excess DAT into presynaptic neuron (15% higher than in controls) – Spencer TJ, Biederman J, Ciccone PE, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry. 2006;163(3):387-395.
  14. 14. Spencer TJ, et al. PET study examining pharmacokinetics, detection and likeability, and dopamine transporter receptor occupancy of short- and long-acting oral methylphenidate. Am J Psychiatry. 2006;163(3):387-395. Graphic from CNS Spectr. 2007;12:4 (Suppl 6): 6- 7
  15. 15. Seidman LJ, Valera EM, Makris N, et al. Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging. Biol Psychiatry. 2006;60(10):1071-1080. • Population: – 24 adults with ADHD per DSM-IV – 18 controls • Relative to controls: – significantly smaller overall cortical gray matter, prefrontal and ACC volumes. Graphic from CNS Spectr. 2007;12:4 (Suppl 6): 6- 7
  16. 16. Narr KL, et al. J Am Acad Child Adolesc Psychiatry. Oct 2009; 48(10): 1014–1022. • Population: – 22 children & teens with ADHD per DSM-IV – on no Rx – 22 controls – mean age of 11.7 years in both groups) • Relative to controls: – Significant volume reduction in overall brain, gray matter, & mean cortical thickness. – White matter volume significantly increased.
  17. 17. Narr KL, et al. J Am Acad Child Adolesc Psychiatry. Oct 2009; 48(10): 1014–1022. “Cortical thickness reductions present a robust neuroanatomical marker for child and adolescent ADHD. Observations of widespread cortical thinning expand on earlier cross-sectional findings and provide further evidence to support that the neurobiological underpinnings of ADHD extend beyond prefrontal and subcortical circuits.”
  18. 18. Prevalence & diagnosis
  19. 19. (NYT, 12 14 2013)
  20. 20. What does it “look like”? A section for kinesthetic and visual learners…
  21. 21. ADHD – not concentrating Inferior Orbital pre-frontal cortex Images courtesy of Daniel Amen, MD – Amen Clinics, Inc., Newport Beach, CA
  22. 22. ADHD - concentrating
  23. 23. ADHD – concentrating, on RX
  24. 24. ADD – inattentive, without Rx ADD – inattentive, on Amph Images courtesy of Daniel Amen, MD – Amen Clinics, Inc., Newport Beach, CA
  25. 25. Diagnostic criteria
  26. 26. DIAGNOSIS: FOUR FLAVORS OF ADHD 314.00 ADHD Predominantly Inattentive Type* 314.01 ADHD Predominant Hyperactive- Impulsive Type* 314.04 ADHD, Combined Type 314.9 ADHD – Not Otherwise Specified 5-6 of 9 symptoms required for 314.00 & 314.01
  27. 27. – Symptoms present before age 7 (now 12 in DSM-5) years – Impairment from symptoms present in 2 or more settings – Significant social, academic, or occupational impairment – Exclude other mental disorders PATIENT NAME: ___________________________ DATE: __________ Medication status: ( ) pre-treatment? ( ) on Rx? ( ) OFF of Rx? Check off the symptoms which are unusually troublesome for your child (or YOU, if you are an adult patient) which are clearly different from what other children or adults typically experience. PLEASE USE THE BACK SIDE OF THIS FORM TO AMPLIFY ON ANY OF THE "CHECKED" SYMPTOMS WHICH YOU FEEL I SHOULD KNOW MORE ABOUT. medication size of dose WHEN TAKEN ADHD Diagnostic Symptom Checklist, adapted from DSM-IV, by: Louis B. Cady, M.D. - 611 Harriet Street - Suite 304 - Doctors Plaza Evansville, IN 47710 PATIENT STATUS: CHILD ATTENTION PROBLEMS displays failure to give close attention to details; makes careless mistakes has difficulty with sustained attention doesn't listen even when spoken to directly has REAL trouble following through on instructions; fails to finish tasks difficulty organizing tasks/activities avoids, dislikes, or reluctant to engage in tasks requiring sustained mental effort (homework, work projects, etc.) loses things necessary for tasks/activities easily distracted by extraneous stimuli (sounds or sights in the environment) often forgetful in daily activities HYPERACTIVITY, "WIGGLESOMENESS" PROBLEMS fidgets with hands or feet, squirms in seat leaves seat in classroom in which remaining in seat was expected, or can't stay put at work runs about; climbs excessively in inappropriate situations difficulty playing or engaging in leisure activities quietly often was "on the go" as if "driven by a motor" talks excessively - a "chatterbox" PROBLEMS BEING IMPULSIVE blurts out answers before questions are completed difficulty waiting your turn interrupts or intrudes on others (butts into conversations) For physician use only - RECENT CLINICAL HISTORY: PARENTS: Please feel in your child's CURRENT DRUG THERAPY... PLEASE LIST! ____________ _________ ____________ ____________ _________ ____________ ____________ _________ ____________ ____________ _________ ____________ ____________ _________ ____________ ____________ _________ ____________ ____________ _________ ____________ physician use...
  28. 28. DSM-5 update • 6 symptoms before age 7 • 6 symptoms for adults • 6 symptoms before age 12 • 5 (FIVE) symptoms for adults
  29. 29. “The Total Picture” diagnostic pearls [from Steven Grcevich, MD] • Read comments on report cards! • Ask siblings: “What’s (s)he like to live with?” • Ask patient: “When was the last time you got invited to someone else’s house to play?” • Ask parents: “Is (s)he involved with any activities in the community?”
  30. 30. Cf: for 20 minute explanatory video
  31. 31. D iagnosis & The Four D’s of Malpractice • D uty • D ereliction of the duty • D amages resulting • D irectly caused. (“proximate cause”) Our call to be better doctors and health care providers. PS: Chart SCRUPULOUSLY.
  32. 32. August 5, 2014 Allegedly: •Improper diagnosis •Failure to monitor use of Adderall – Prescribed increasing doses of Adderall in spite of signs of drug abuse. •Ultimately leading to patient’s suicide.
  33. 33. Don’t get it wrong. ADHD confounds: • Autism spectrum disorder • Hearing impairments • Hypothyroidism • Iron deficiency anemia • Lead toxicity • (OSA)
  34. 34. Constantin E et al. Association between childhood sleep-disordered breathing and disruptive behavior disorders in childhood and adolescence. Behav Sleep Med. 2014 Aug 7:1-13. • 605 children: 19% snored, 10% had OSA. • 13% had ADHD diagnosis • 5-9% had behavioral problems or conduct disorder • OSA symptoms were associated with: –Two-fold increased risk of ADHD dx or sxs. – 3 – 4X increased odds of behavioral problems or conduct disorder
  35. 35. MISS-Diagnosis and MISdiagnosis • MISSing it – Not taking a good history or using rating scales – Not taking a family history. – Poor documentation – Not testing • MISdiagnosing ADHD – “all that wiggles is not ADHD.” – “all that is inattentive and can’t concentrate is not ADHD.” – Don’t miss medical. – EXCLUDE Bipolar, depression, anxiety d.o., “EFAD,” PTSD, sexual trauma • (and CHART CHART CHART)
  36. 36. Different symptom manifestation: children through adults
  37. 37. Continuation of Impairment of ADHD Childhood    Adulthood Job failure or under-employment School failure / under- Becomes achievement Fatal car wrecks / risk taking Multiple injuries Becomes Drug experimentation Becomes Drug dependence ASPD, criminal involvement ODD / CD Becomes Unwanted pregnancy, Becomes STDs, etc. Hopelessness, Impulsivity and carelessness Repetitive failure Becomes frustration, giving up Courtesy of William Dodson, MD – Denver, Colorado
  38. 38. ADHD: Course of the Disorder Inattention Hyperactivity —Age— Impulsivity
  39. 39. Earlier Initiation of Smoking with ADHD 237 6 to 17-year-old boys 0.6 0.5 0.4 0.3 0.2 0.1 0 Smoking probability 0 2 4 6 8 10 12 14 16 18 20 22 24 P<0.003 ADHD n=128 Control n=109 4 year follow-up Milberger S, et al. J Am Acad Child Adolesc Psychol. 1997;36:37-44.
  40. 40. Increased Lifetime Substance Abuse in Untreated Adults with ADHD 60 Lifetime rate of substance abuse in referred ADHD adults 0 50 40 30 20 10 ADHD (n=239) 55% Control (n=268) P<0.001 27% Biederman, et al. Biol Psychiatry. 1998;44:269-273.
  41. 41. Pharmacotherapy Significantly Reduces Substance Abuse in Adults 40 32 with ADHD population 30 study 20 of % 10 0 Unmedicated ADHD P<0.001 3-fold! 12 10 Medicated ADHD Control (N=19) (N=56) (N=137) Biederman J, et al. Pediatrics. 1999;104:e20-e25.
  42. 42. What happens if ADHD isn't treated?
  43. 43. Outcomes of kids with ADHD as adults • Significantly worse educational, occupation, economic, and social outcomes • More divorces • Higher rates of ongoing ADHD (22.5% vs. 5.1%) • More antisocial personality disorder (16.3% vs. 0%) • More SUD’s (14.1% vs. 5.1%) • “The multiple disadvantages predicted by childhood ADHD well into adulthood began in adolescence without onsets of new disorders after 20 years of age.” Klein RG, Mannuzza S, et al. Clinical & functional outcome of childhood attention-deficit/hyperactivity disorder 33 years later. Arch Gen Psychiatry 2012 Dec;69(12):1295-303. doi: 10.1001/archgenpsychiatry.2012.271.
  44. 44. Horrigan J, et al. Presented at 47th Annual AACAP Meeting: October 24-29, 2000. New York, NY.
  45. 45. Driving behavior and results in 27 clinically referred German adults • N=27, with initial screen – 19 studied – initial testing then either: • 10- kept medication free • 9 – tx’ed for 6 weeks with MPH Sobanski E, et al. Driving-related risks and impact of metylphendiate treatment on driving in adults with attention-deficit/hyperactivity disorder (ADHD). J Neural Trans. 2008; 115(2):347-56.
  46. 46. Driving behavior and results in 27 clinically referred German adults • Background findings: – All ADHD subjects: drove significantly more kilometers per year – More often registered by traffic authorities – Fined more frequently – Involved in more MVA’s – Self described driving style as “more insecure and hectic” than controls. • A high risk group was delineated with: – 3-6 MVA’s per ADHD subject Sobanski E, et al. Driving-related risks and impact of methylphenidate treatment on driving in adults with attention-deficit/hyperactivity disorder (ADHD). J Neural Transm.. 2008; 115(2):347-56.
  47. 47. Do you want to treat them? STUDY CONCLUSIONS: MPH tx improved information processing and sustained visual attention compared to baseline and untreated control groups. Sobanski E, et al. Driving-related risks and impact of metylphendiate treatment on driving in adults with attention-deficit/hyperactivity disorder (ADHD). J Neural Trams. 2008; 115(2):347-56.
  48. 48. Psychiatric disorders (lifetime) in adults with ADHD [multiple sources, % is estimated; N.B. – this is WITHOUT TREATMENT GROWING UP] • Substance use disorders (all) 50% • Anxiety disorders 40% • Major depression 35% • Learning disabilities 20% • Bipolar disorder 10% • Antisocial disorder 10%
  49. 49. 105 Adult ADHD Drivers vs. 64 Controls (CC) • ADHD’ers self reported: – More citations (esp. for SPEEDING), crashes & license suspensions than CC • ADHD’ers: – less attentive, made more errors on visual reaction task – Lower scores on driving rules test. • Driving difficulties: not related to “ODD”, depression, anxiety, or frequency of substance use. Barkley RA, et al. J Int. Neuropsychol Soc. 2002 (5):655-762.
  50. 50. Adult ADHD’ers: • Lower self esteem as adults • Lower educational achievements • Greater use of ancillary educational resources • Greater tobacco and recreational drug use • A lifelong pattern of “consistent inconsistency.” Source: David Goodman, MD – Johns Hopkins Adult ADHD treatment center
  51. 51. Drug, drug... who's got the drug?
  52. 52. We are not there yet.
  53. 53. Response to Psychostimulants Meta-analysis of Within-Subject Comparative Trials Evaluating Response to Stimulant Medications 50 40 30 20 10 0 Best Response (Percent) AMP MPH Equal response to either stimulant 2288%% 1166%% 4411%% .Arnold et al. J Attention Dis. 2000;3:200. Betting odds: Amph – 69% MPH 57%
  54. 54. Benefit-Risk Ratio and Efficacy of Psychostimulants • Very favorable benefit-risk ratio – rapid, dramatic results – low risk of long-term side effects • Approximately 70% of patients with ADHD will show a positive response on the first trial of any one stimulant medication • If two different stimulant medications are tried, the response rate increases to ~90% Greenhill. Child Adolesc Psychiatr Clin North Am. 1995;4:123; Spencer et al. JAACAP. 1996;35:409; Goldman et al. JAMA. 1998;279:1100.
  55. 55. Amphetamines, methylphenidate, and antidepressants - important differences: Amphetamine - increases release and decreases uptake at the DOPAMINE uptake transporter (Seiden, et al., 1993) –effects release of DA from vesicles. –also allows dopamine to be released from newly synthesized pools inside the cell. –also activates 5-HT receptors (Sloviter, et al., 1978) –L-amphetamine = 50/50 NERI/DRI (Stahl, 2013) Methylphenidate - effects release of DA from vesicles only – inhibits dopamine reuptake, as well. Antidepressants: inhibit reuptake of NE and DA; do not cause release. [Atomoxetine = “NRI”]
  56. 56. Atomoxetine • Superior to placebo (but slightly less effective than MPH) in large, double-blind, placebo-controlled trial-Heiligenstein, 2000 HCl • Spencer et al. (JCAP 2001)-open study, CH3 O N 30 patients, 75% improved >25%. H CH3 SE’s: rhinitis, headache, anorexia, dizziness, nervousness, somnolence • Michaelson (Pediatrics, 2001) ATX>PLB, best response at 1.2 mg/kg/day • Kratchovil (JAACAP, 2002) ATX=generic MPH, open-label study, inadequately powered Heiligenstein et al. Presented at AACAP, October 24-29, 2000 Spencer et al. J. Child Adolesc Psychopharmacol 2001: 11(3) 229-238
  57. 57. “Strattera* [coupled with fluoxetine or paroxetine] has been great for our admissions.” -Dr. William Beute, MD Pine Rest Campus Clinic Grand Rapids, MI April 21, 2004 [quoted with permission] * Brand name used in this slide because this is a direct quote
  58. 58. “2P, or not 2P… …that is interaction.” NB: Cytochrome p450 2D6: -This is where atomoxetine is metabolized -It is inhibited by paroxetine and fluoxetine
  59. 59. “Alpha 2a agents” • Concept of SUSTAINED RELEASE AGENTS – generic instant release agents not the same • Extended release guanfacine – “1,2,3 or 4 mg at bedtime” • Extended release clonidine – “0.1 – 0.2mg (ER) twice daily (a.m. and pm)” • Both are approved for monotherapy or for add-on therapy. • Stimulants seem more potent; alpha-2 Rx seems to be better for oppositional/defiant symptoms, either by themselves or in combination therapy.
  60. 60. “Mixed salts of amphetamines, "handedness,” and efficacy Amphetamine mixed salts contains: –d - amphetamine sulfate (aka "Dexedrine") –d,l - amphetamine sulfate –d,l - amphetamine saccharate –D,l – amphetamine aspartate Dextro-amphetamine 2x as effective as l-amphetamine –Smith & Davis, 1977; Janowsky & Davis, 1976
  61. 61. The Arnold studies Randomized, double-blind, placebo controlled 31 children with “MBD” (1976) Rx: 5 mg of d-AMP; 7 mg l-AMP [difference d.t. MW's] CONCLUSIONS (replicated previous 1972 study of n=11): –Both agents found effective –Typically one agent was more effective than the other for individual children [Arnold LE, Huestis RD, Smeltzer DJ, et al. Levoamphetamine vs dextroamphetamine in minimal brain dysfunction. Arch Gen Psychiatry 33:292-301, 1976 Arnold LE, et al. Levoamphetamine and dextroamphetamine: Differential effects on aggression and hyperkinesis in children and dogs. Am J Psychiatry 130:165-170, 1973]
  62. 62. TTyyppiiccaallllyy oonnee aaggeenntt wwaass mmoorree eeffffeeccttiivvee tthhaann tthhee ootthheerr ffoorr iinnddiivviidduuaall cchhiillddrreenn • dd--AAMMPP ""aappppeeaarreedd nnoonn--ssiiggnniiffiiccaannttllyy mmoorree eeffffeeccttiivvee"" • sslliigghhttllyy bbeetttteerr ffoorr ""oovveerr--aannxxiioouuss"" cchhiillddrreenn • ll--iissoommeerr -- 22//33 ooff cchhiillddrreenn iimmpprroovveedd • sseeeemmeedd ttoo bbee ooff mmoorree bbeenneeffiitt ttoo ""uunnssoocciiaalliizzeedd--aaggggrreessssiivvee"" kkiiddss • 2288%% ooff rreessppoonnddeerrss pprreeffeerrrreedd tthhee ll--AAMMPP ffoorrmm • ““ddeeccrreeaasseedd tteennddeennccyy ttoo bblluunntt aaffffeecctt aanndd pprroodduuccee tthhee ‘‘aammpphheettaammiinnee llooookk’’ [[ssiicc]]””
  63. 63. Drug Delivery & Dosing adjustments
  64. 64. OROS MPH – the first player GI liquid absorbed into osmotic matrix pump MPH pushed out the laser drilled hole at end of tablet
  65. 65. Peaks & troughs… OROS MPH & OROS MPH – 18 mg
  66. 66. Mixed amphetamine salts “XR” system Delayed-Release Bead Immediate-Release Bead Bead Core Bead Core Drug Layer Release-Delaying Polymer Overcoating Capsule Overcoating 50% 50% Drug Layer Overcoating Available in 5, 10, 15, 20, 25, and 30 mg dosing forms
  67. 67. Chemical Structure ooff LLiiss--ddeexxaammffeettaammiinnee H 22N NH22 l-lysine O OH + H 22N CH33 d-amphetamine (active) H 22N O N H NH22 CH33 Site of cleavage Lisdexamfetamine (Prodrug) Rate-limited Hydrolysis LLiiss--ddeexxaammffeettaammiinnee iiss aa pprrooddrruugg tthhaatt iiss tthheerraappeeuuttiiccaallllyy iinnaaccttiivvee uunnttiill iitt iiss ccoonnvveerrtteedd ttoo aaccttiivvee dd--aammpphheettaammiinnee iinn tthhee bbooddyy
  68. 68. Charged polymer sustained delivery technology 12 hour sustained release LIQUID MPH Rx
  69. 69. Basic MPH 101 • How much to Rx?! • Old dosing charts show 0.3 – 0.7 mg/kg/dose – But only “1.5 mg/kg/day”…. • But THREE doses of 0.3 – 0.7 mg/kg/dose = 0.9 – 2.1mg/kg/day • THEREFORE, theoretical maximum should be “2.1 mg/kg/day” (the “Biederman max”) • But what is that really, in “Hoosier-speak”?
  70. 70. Cady/Desiderato Factor-Label, Down- Home, Good-Ole Boy MPH Calculation: 2.1mg MPH 1 Kg ONE milligram X = Kg 2.2 lbs pound of kid 1mg / lb of kid / day spread out over 12 hours, OR About ½ that for amphetamines or dex-MPH amphetamine salts, dex amph, dex- MPH = ½ the typical amount of methylphenidate
  71. 71. So how much to dose? • No correlation between plasma level and therapeutic response: – Big levels in small kids – Small levels in big kids • All medication titrations should be made by informed, observant clinicians with good solid follow-up and examinations • Titrations should be based on DYSFUNCTION
  72. 72. M.D. does not stand for “minor deity” • Start lower than you think you probably should. • Push it carefully until you get results – a “just right” therapeutic effect – absent side effects • Use the “Biederman max” as a rough rule of thumb to calculate the “ceiling,” NOT TO START! • If you have to “break through the ceiling” – think carefully, document your rationale, monitor carefully for side effects, HTN, cardiac issues • Explain both the “Goldilocks” and the “Cinderella” aspects to patients/parents
  73. 73. How to screw it up: a case study • 1/28/14 – 7 year old child presents for tx • Oct 2013 – dx’ed with ADHD • RX: – Started on 30 mg lys-dexamph from start • Zombied out for two days – Dosage reduced to 15 mg. Worked well for 3 weeks. “I like the way my brain is working.” – Began hearing voices in his head at night. • Medication stopped • Voices persisted over the next 2 weeks, then d/c
  74. 74. At home: Two great “how to do it” books
  75. 75. Therapy Axioms: who needs it, when to do it • The later a child (or adult) is diagnosed, the more complications (s)he has had, and the more conflict – the higher the likelihood of need for psychotherapy • The converse applies. • The higher the level of family dysfunction, the more the need for: – “parent training” – Behavioral therapies, etc.
  76. 76. Inventor of NASDAQ screen – Strong family hx of ADHD – Dx’ed at 48 yoa – Interviewed in Time Square – “Don’t you feel proud?” –“Not really – all my life, people were telling me I would never amount to anything.” Quote & identity used by specific permission of David Goodman, MD [Dir., Adult Attention Deficit Disorder Center of Maryland] & his patient
  77. 77. Integrated: how to avoid over-reliance on meds • Holistic treatment and supplementation! – Cf: The Physician in Spite of Himself, Part II • Smart prescribing! • School: – Excellent working relationships with school – Good teaching • HOME: – Diminish “electronic screens” effect – Good home discipline – Good sleep/wake schedules – Good diet – Adequate exercise • Parent training: parenting, stress tips
  78. 78. New Concepts in the Epidemiology, Diagnosis and Precision Treatment of ADHD in Children, Adolescents, and Adults But what about the functional medicine aspects?? What happened ttoo tthhoossee,, aannyywwaayy??!! IMMH 5th Annual Conference San Antonio, TX Sunday, Sept. 21
  79. 79. My Previous Notion of Therapeutic Options
  80. 80. My experience with a child with out of control ADHD - the story of Billy • 8/1998 – 4 yo Eastern European adopted child – “ADD & behavioral problems, destructive.” – First 3 years of life in orphanage • Fam Psych Hx: – Dad – “substance induced paranoid psychosis” – Mother – “recurrent schizophrenic decompensations”
  81. 81. Billy, cont. • Some improvement • 3/1999 – increasingly vile temper. Sad, dysphoric. “Back to square one.” – Zoloft added. – Ritalin only lasting 1 ½ hours • 5/1999 - 4 ½ yoa. Rehab Center testing: – Auditory comprehension = 2 y 11 mo’s – Total language = 2 y 11 mo’s • 6/1999 – Flaxseed oil, L-tyrosine, Pediactive tabs added. In constant trouble Dad getting depressed.
  82. 82. Billy, cont – 1999 - 2000 • Ritalin and Adderall not working • Temper to the point of clawing at his face. Sniffing. Now urinating in bed. • 12/1999 – started on Risperdal – 1mg in a.m. and ½ mg later in day • 2/2000 – Psych testing – IQ 78 – ADHD – Borderline intelligence – Processing problems – “r/o childhood psychosis”
  83. 83. Billy, late 2000 • Fall 2000: – Bit and stabbed his teacher with a pencil, kicked chair, wall, and desk, spat on floor and teacher. Obsessively lining up his cars in his room, tongue thrusting and smacking (? Tardive dyskinesia?) • On Risperdal, Depakote, and Concerta. • 8/2001 – 2002 some better but still unpredictable. Meltdowns. Depakote increased. Zyprexa added. • 8/2002 – throwing things against windows. Depakote not working. Mood cycling.
  84. 84. Billy, 2003 • Ongoing unpredictability until Geodon started. – Less hyper – Dry in a.m. – Clearer speech and better eye contact. • July 2003 – IgG food allergy testing ordered
  85. 85. Billy – IgG Food Sensitvities July 2003 • 21 + IgG reactions.. Of these….. – Cheese (3+) – Cow’s milk (3+) – Goat’s milk (2+) – Brewer’s yeast (3+) – Millet (+1) – Lettuce (!) (+1) Reviewed labs with internet savvy Mom (who did NOTHING).
  86. 86. June 7, 2004 – 6 years of tx; ONE YEAR AFTER IgG Testing! • “Literally bouncing off the walls in the a.m.” • Almost knocked brother off second floor balcony • Could not tolerate < 2 g VPA • Threw stool over banister and tried to hit Mom on way up stairs. (Missed) • Told Mom: “You’re going to die, I’m going to make sure you’re going to die.” • Things that make him angry: not putting peanut butter sandwich on plate “correctly.” • Waking up screaming. Making non-human, guttural sounds. • Parents pursuing IP treatment
  87. 87. Radical interventions/ workup • June 2004 – Lithium added – Made him briefly toxic but symptoms improved. – Worked on getting him inpatient tx. • Fatty acid panel ordered. • Told Mom to GET SERIOUS about food allergies/sensitivities
  88. 88. Clinical manifestations of EFAD • Dermatitis • Increased appetite and caloric intake in infants (adults?!) • Failure of wound healing • Irritability • Alopecia, dry hair, dandruff • Brittle nails • Increased susceptibility of infections • Thirst, polydipsia, polyuria • Liver fatty infiltration • Increased capillary fragility • RBC fragility • Increased Cholesterol/HDL ratio
  89. 89. Essential Fatty Acid findings Value Reference range EPA 3 (L) 20 - 80 DHA 32 (L) 70 - 150
  90. 90. FEB 2005
  91. 91. • The present study found that 53 subjects with ADHD had significantly lower concentrations of key fatty acids in the plasma polar lipids (20:4n-6, 20:5n-3, and 22:6n-3) and in red blood cell total lipids (20:4n-6 and 22:4n-6) than did the 43 control subjects • “…but the precise reason for lower fatty acid concentrations in some children with ADHD is not clear.”
  92. 92. • “We argue that a change in the ratio of n-6/n-3, especially during early life, may induce developmental changes in brain connectivity, synaptogenesis, cognition and behavior that are directly related to ASD.”
  93. 93. • Western diet: omega 3 fatty acid deficiency and increased fructose intake. • “Both promote brain insulin resistance and increase the vulnerability to cognitive dysfunction.” • “Multiple cognitive domains are affected by metabolic syndrome in adults and in obese adolescents, with volume losses in the hippocampus and frontal lobe, affecting executive function.”
  94. 94. • In Adults with ADHD: • DECREASED DHA, AA, and DHGLA • “We could demonstrate that a lack of polyunsaturated FAs in blood serum of subjects with ADHD persists into adulthood. Furthermore, we could show that adult ADHD symptomatology positively correlates with elevated levels of saturated stearic and monounsaturated FAs.HGLA were lower than controls.”
  95. 95. This summary demonstrates that a deficiency in brain PUFAs will lead to cognitive deficits, while supplementation of PUFAs can rehabilitate cognitive deficits, as manifested in attention deficit hyperactivity disorder, stress/anxiety, and aging.
  96. 96. Should we use this??
  97. 97. Further elongation problems: lack of nutrients • REQUIRED for delta-6 desaturase: – Magnesium – Zinc – B vitamins • FAD (B2) • Niacin (B3) • P-5-P (B6) – C – insulin “chiropractic” “psychiatric”
  98. 98. Extra slide of online viewing • Key principles of essential fatty acid supplementation are: – Do not use large doses of a generic omega 6 or omega 3 fish oil and presume that you are going to get adequate amounts of EPA and DHA out the bottom of the pathways. – The only two sources of fish oil high in PUFA’s that we get are from eating fish or taking fish oil. Period. If we don’t eat fish, we should probably be on fish oil. – We DO have the ability to synthesize the critical PUFA’s, including EPA and DHA, from precursors, but in order to do so, we must have adequate amounts of the critical trace minerals.
  99. 99. NOTE: The essential elements portion of this test include: •Elemental lithium •Iron •Magnesium •Zinc •copper
  100. 100. IRON - Most common of all nutrient deficiencies in U.S. school-aged children Murray & Pizzorno. Encyclopedia of Natural medicine. Rocklin, CA: Prima Publishing; 1998. 45 • Deficiency associated with: markedly decreased attentiveness, narrower attention span, decreased persistence, and lowered activity level – all of which respond positively to supplementation. • Kidd. ADHD in Children: Rationale for Its Integrative Management. Alt Med Review 2000; 5(5):402-427. • 30% improvement in Conners ADHD Rating Scale following iron supplementation [(Ferrocal), 5 mg/kg/day for 30 days] in one uncontrolled Israeli study of boys. 40 35 30 25 20 15 10 • Sever et al. Iron treatment in children with attention deficit hyperactivity disorder. A preliminary report. Neuropyshcobiology 1997;35:178-180. 5 0 serum ferritin Conners before after –significant increase in serum ferritin levels (from 25.9 +/- 9.2 to 44.6 +/- 18 ng/ml) and a significant decrease on the parents' Connors Rating Scale scores (from 17.6 +/- 4.5 to 12.7 +/- 5.4).
  101. 101. Zinc link --- and friends • Psychiatr Pol 1994 May-Jun;28(3):345-53 [Deficiency of certain trace elements in children with hyperactivity] [Article in Polish]Kozielec T, Starobrat-Hermelin B, Kotkowiak L. Zakladu Medycyny Rodzinnej Pomorskiej Akademii Medycznej. • The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group--healthy children from Szczecin. The highest deficit was noted in hair. • Our results show that it is necessary to supplement trace elements in children with hyperactivity.
  102. 102. Magnes Res 1997 Jun;10(2):143-8 Kozielec T, Starobrat-Hermelin B.,, 1997, cont. • 116 children with ADHD • Magnesium deficiency was found in 95 per cent of those examined: – most frequently in hair (77.6 per cent) – in red blood cells (58.6 per cent) – and in blood serum (33.6 per cent) • CONCLUSIONS: magnesium deficiency in children with ADHD occurs more frequently than in healthy children. Analysis of the material indicated the correlation between levels of magnesium and the quotient of development to freedom from distractibility.
  103. 103. “Don’t think ‘either/or.’ Think ‘both/and.’” - Dan Burrus
  104. 104. “There are things known and there are things unknown, and in between are the doors.” - Jim Morrison
  105. 105. Contact information: Louis B. Cady, M.D. Office: 812-429-0772 E-mail: 4727 Rosebud Lane – Suite F Interstate Office Park Newburgh, IN 47630 (USA)