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Controversies Regarding Attention Deficit Hyperactivity Disorder Presented by: Dr. Kevin Nugent Child & Adolescent Psychiatrist ([email protected]) Disclosure Statement No research involvements. No financial involvements with pharmaceutical companies. Have made educational presentations sponsored by: SmithKline Beecham (Paxil) Janssen-Ortho (Concerta) Shire (Adderall XR, Vyvanse, Intuniv XR) Purdue (Biphentin) Astrazeneca (Seroquel) Otsuka (Abilify) Advisory Board involvement: Shire ADHD Controversies: General Scepticism Why all the recent “fuss’ about it? All kids can get hyper! Does it even exist? “But they can play lego/video games for hours!” Is it a “real” medically-based disorder? Is it a mental illness? How important is it really? Don’t kids “grow out of it” anyway? “They said I had it and look how well I turned out!” All we talk about are the negatives…is there nothing positive about ADHD? ADHD Controversies: More Specific Questions Why do professionals disagree about diagnosis and treatment? My child has anxiety, ASD, LD, been through our marriage breaking up, etc. so wouldn’t that explain the ADHD-like symptoms. Aren’t dietary, “natural” or alternative measures safer/ better? Aren’t meds for ADHD experimental/unsafe /over-emphasized/ addictive/ more for teacher’s benefit/ turning kids into “zombies’? Why would you give hyper kids “stimulants”? Will ADHD meds make them “addicted” or more likely to turn to illicit drugs? The medication didn’t work so my child must not have ADHD Should medication be given continuously or can it just target school days? Historical perspective This set of difficulties has been identified for over 100 years: “Fidgety Phil” described by Hoffman in 1846. In 1902, Still described 20 kids from “good homes with good parents” with classic ADHD. -3/1 male to female ratio -questioned a likely biological/ genetic cause. Historical perspective Name has evolved: -Organic Drivenness (30’s) -Minimal Brain Damage/ Dysfunction (50’s) -Hyperactivity or Hyperkinesis (60’s) -ADD +/- Hyperactivity or Residual State (80’s) -ADHD (predominantly Inattentive subtype, predominantly Hyperactive-Impulsive subtype or Combined type) -ADHD (Inattentive, H-I or Combined presentation) Core Difficulties Inattention= Trouble focusing, sustaining and shifting attention, distractibility, poor following of instructions and ease of boredom Disorganization and time management/ procrastination Elevated activity level (motoric +/- verbal) Impulsivity (behavioral, verbal and cognitive) Impatience and poor frustration tolerance/ anger management Emotional excitability and reactivity Relative social and emotional immaturity Prevalence and Persistence of ADHD Children Ranges from 3-12% Approx. 70% receive treatment 70% persistence of ADHD into adolescence Up to 60% persistence of ADHD into adulthood (though adults under-estimate their symptoms) Hyperactivity and impulsivity likely improve with age Adults US epidemiology study: 4.4% WHO epidemiology study: 3.4% (range 1.2-7.3%) Fewer than 17% receive treatment Wender et al. NY Acad Sci, 2001; Wender H. Arch Pediatr Adolesc Med, 2002 Kessler et al. J Occup Environ Med, 2005; Fayyad et al. Br J Psych, 2007 ADHD Types: Childhood vs. Adulthood Inattentive Type Combined Type 22% 56% Inattentive Type 44% Combined Type 78% In Childhood In Adulthood Spencer, 2005, Harvard Update; McGough, Smalley, McCracken et al. American Journal of Psychiatry. September 2005, Vol. 162, Page 1621 Delayed brain growth in ADHD (3 yrs.) From Shaw, P. et al. (2007). ADHD is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences, 104, 19649-19654. Greater than 2 years’ delay 0 to 2 years delay Ns: ADHD=223; Controls = 223 Biological Underpinnings Statistically a difference in the size and/ or activation of the following areas of the brain of children with ADHD: -basal reticular formation (level of arousal and concentration) -prefrontal cortex (executive functions and problemsolving) -basal ganglia and cerebellum (control of motor activity) Neurotransmitters norepinephrine and dopamine modulate these circuits Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset Global and regional glucose metabolism by PET scan reduced in adults who have been hyperactive since childhood Largest reductions in: Premotor cortex Superior prefrontal cortex Copyright © 1990 Massachusetts Medical Society. All rights reserved; permission pending. Zametkin AJ et al. Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset. N Engl J Med. 1990 November;323(20):1361-6. Normal With ADHD Anterior Cingulate (Cognitive Division) Fails to Activate in ADHD Normal Controls y = +21 mm 1 x 10-2 ADHD Adults y = +21 mm 1 x 10-3 MGH-NMR Center and Harvard - MIT CITP Bush et al. Anterior cingulate cortex dysfunction in attention-deficit/hyperactivity disorder revealed by fMRI and the Counting Stroop. Biol Psychiatry. 1999 Jun;45(12):1542-52. 1 x 10-2 1 x 10-3 Heritability Co-efficient of ADHD Breast cancer Asthma Schizophrenia Height Hudziak, 2000 Nadder, 1998 Levy, 1997 Sherman, 1997 Silberg, 1996 Gjone, 1996 Thapar, 1995 Schmitz, 1995 Edelbrock, 1992 Gillis, 1992 Goodman, 1989 Willerman, 1973 0 0.2 0.4 0.6 0.76 Average genetic contribution based on twin studies ADHD Mean Faraone SV. J Am Acad Child Adolesc Psychiatry. 2000 Nov;39(11):1455-7. Hemminki K, Mutanen P. Mutat Res. 2001 Jan;473(1):11-21; Palmer LJ et al. Eur Respir J. 2001 Apr;17(4):696-702. 1 Other Genetic Evidence Adoption studies: Higher incidence of ADHD in biological relatives if adopted child has ADHD (even if adoptive parents do not) ADHD Concordance Rate is >80% in identical twins and 31% in fraternal twins If parent has ADHD, 20 to 54% of offspring will exhibit some form of ADHD If a child has ADHD, 25% chance that one of their parents will have ADHD Etiologies of ADHD From Joel Nigg (2006), What Causes ADHD? Other Perinatal Smoking Lead FASD LBW Heritable (Genetics) Heritable LBW FASD Lead (high) Smoking Perinatal Other (Toxins) Co-occurring Disorders in Children ADHD alone 31% Tics 11% Conduct Disorder 14% Mood Disorders 4% MTA Cooperative Group. Arch Gen Psych 1999; 56:1088–96 Oppositional Defiant Disorder 40% Anxiety Disorder 34% (n=579) Potential ADHD Overlaps Sleep Disorders Developmental Delays (esp. speech and language and motor coordination) Fetal Alcohol Spectrum Disorders Specific Learning Disabilities (10-60%) Central Auditory Processing Disorders Attachment Disorders Post-traumatic Stress Disorders Making ADHD Diagnosis Child’s function and extent of related symptoms in child’s key environments Need for qualitative, behavioral questionnaires and info from the school Office observation not reliable/ sufficient. Functional impairment! Other developmental/ learning/ MH issues Medical/ Family Mental Health/ etc. The SNAP-IV Teacher and Parent Rating Scale 1. Often fails to give close attention to details or makes careless mistakes in schoolwork or tasks 2. Often has difficulty sustaining attention in tasks or play activities 3. Often does not seem to listen when spoken to directly 4. Often does not follow through on instructions and fails to finish schoolwork, chores, or duties 5. Often has difficulty organizing tasks and activities 6. Often avoids, dislikes, or reluctantly engages in tasks requiring sustained mental effort 7. Often loses things necessary for activities (e.g., toys, school assignments, pencils, or books) 8. Often is distracted by extraneous stimuli 9. Often is forgetful in daily activities 10. Often fidgets with hands or feet or squirms in seat 11. Often leaves seat in classroom or in other situations in which remaining seated is expected 12. Often runs about or climbs excessively in situations in which it is inappropriate 13. Often has difficulty playing or engaging in leisure activities quietly 14. Often is "on the go" or often acts as if "driven by a motor" 15. Often talks excessively 16. Often blurts out answers before questions have been completed 17. Often has difficulty awaiting turn 18. Often interrupts or intrudes on others (e.g., butts into conversations/games) 19. Often loses temper 20. Often argues with adults 21. Often actively defies or refuses adult requests or rules 22. Often deliberately does things that annoy other people 23. Often blames others for his or her mistakes or misbehaviour 24. Often touchy or easily annoyed by others 25. Often is angry and resentful 26. Often is spiteful or vindictive 27.-39. Additional items from DSM-III (1980) and DSM-III-R (1987) Swanson et al. JAACAP 2001;40:168-79 Overview of Diagnostic Concerns re. ADHD A more careful diagnostic process, preferably one with use of quantifiable behavioral questionnaires and school input, is highly recommended. Need to understand that this is a “spectrum disorder” and that there can be some situational influence on severity of symptoms. A very significant overlap with many other learning and mental health struggles means we should be open to this likelihood and be prepared to review these matters carefully over time. Issue of not over-stepping professional expertise. Consideration for a second opinion or advocating for a psychoeducational assessment. Significant Long-term Impact of ADHD in Adolescents 60 ADHD Controls 50 Subject % 40 30 20 10 0 Failed grade Less than high school Stealing Arrested Substance Abuse Teen pregnancy Barkley et al. JAACAP 1990;29:546-57; Biederman et al. J Pediatr 1998;4:544-1; Barkley R. Attention-deficit hyperactivity disorder. A handbook for diagnosis and treatment, 2nd ed., 1998; Biederman J, et al. Arch Gen Psych 1996;53:437-46; Weiss G, et al. JAACP 1985;24:211-20; Satterfield JH, Schell A. JAACAP 1997;36:1726-35 Potential Domains of Impairment in Adolescent and Adult ADHD Occupational functioning Educational functioning Interpersonal/social functioning Dating, sexual or relationship functioning Managing personal finances Driving a motor vehicle Obedience to provincial/federal laws (e.g., criminal conduct) Managing own children Managing household Managing substance use (responsible use of legal substances) Health maintenance (e.g., exercise, diet, weight control) Note: DSM-IV criteria 3 & 4 - Impairments R. Barkley, 2003 Outcomes Regarding Education and Employment More likely to repeat a grade More likely to not complete High School Less likely to complete university degrees Enter workforce less skilled More likely to be fired Change jobs more often Lower work performance Outcomes Regarding Sexuality (Barkley) Sexual risks: ADHD individuals… -Sexually active earlier (15 vs 16 y) -More sexual partners ( 13.6 vs 6.5) -Less time per partner -Less likely to employ contraception -Greater teen pregnancy (38 vs 4%) -Higher risk for STD’s (16 vs 4%) Young Adults With ADHD Have Increased Risk for Traffic Violations and Accidents Subjects Responding Yes (%) Negative Driving Outcomes From a Driving History Interview 70 P =0.003 ADHD (n=105) 60 Control (n=64) 50 40 30 P =0.001 20 P =0.001 P =0.002 P =0.007 10 0 Drove before licensed 12 or more traffic citations Barkley RA, et al. J Int Neuropsychol Soc. 2002;8:655-672. 5 or more speeding citations License suspended or revoked 3 or more vehicular crashes Other Elevated Risks Smoking Risk: More likely to smoke, start earlier and have a harder time quitting as adults Other addictive behaviors (Video games! Pornography. Gambling.) Other health risks have been documented (from increased accidents to dental care to obesity) Lifetime Risk for other Conditions in Individuals with ADHD Anxiety Disorders (40%) Major Depression (35%) Learning Disabilities (20- 60%) Bipolar Disorder (15%) Antisocial PD (10%) Substance Use Disorder (50% & possibly as high as 10% by 20y) Shekim et al., 90 & Biederman 93 Are there some good aspects about having ADHD? ADHD Treatment Medications should be considered as one component of a multi-modal intervention with school and learning, parenting, behavioral, self-esteem, social skills, anger management, recreational, etc components (as per the needs of a particular child). However, no other intervention has been shown to have more than a modest impact on core ADD and ADHD symptoms. An enormous amount of research documents the effectiveness (80 to 90%), robust impact, and safety of medication intervention for ADHD. This is the most studied area in Child Mental Health. Other Proven Treatments Parent Education/ Support or groups about ADHD Parent Training in Child Management, especially with co-morbid ODD or CD (responses of 6575% if <11 y., <30% if teens) Family Therapy with Teens (30% respond) Teacher Education & Training in Classroom Behavior Management Special classes or Residential Treatments ? Alternative Treatments In contrast, evidence about helpfulness of dietary restriction (food “allergy” or “sensitivity”) is that this has only a slight impact on a small number of children (perhaps 5 %). Similarly the only food supplements with some evidence of their helpfulness (Omega-3 and Evening Primrose Oil) suggest a modest impact for some children. If alternative treatments are considered, they should be monitored and time-limited trials, preferably done independent of medication trials. Consider vitamin or nutritional supplements if child’s nutritional intake is suspect. Other Unproved/ Disproved Therapies Megavitamins, Anti-oxidants, Minerals, Blue green algae, etc. (no proof) Sensory Integration Training (disproved) Chiropractic Manipulation and Naturopathic Treatments (no proof) Play Therapy/ Psychotherapy (disproved) Cognitive Therapies (some limited impact in children) Neurofeedback (being researched) Recommended Interventions Healthy nutrition (Vitamins and other as needed supplements) Good sleep habits (melatonin if required) Exercise! Ongoing involvement in positive recreational pursuit! Limit video games and screen time Parental control software New Medication Options Recent addition of long-acting stimulants: Concerta = up to 12 hr. methylphenidate Biphentin = 8 to 12 hr. methylphenidate Adderall (or MAS) XR = 10 to 12 hr. dextroamphetamine and amphetamine salts Vyvanse (mg.)= dextroamphetamine made available by body processing (non-abusable) Stimulants can target school days only/ mainly. Officially approved non-stimulant preparations: Strattera (atomoxetine, an SNRI) Intuniv XR (guanafacine XR, an alpha-2 adrenergic agonist) Require continuous administration but more 24x7 assistance In ADHD Stimulants Found to Improve: Core Symptoms Attention (on-task behavior, efficiency, accuracy, memory and neatness) Impulsivity Hyperactivity (less interrupting, fidgetiness) Anger and aggression ADHD Practice Parameters. JAACAP 1997; 36:85S Zametkin and Ernst. N Eng J Med 1993; 340:40 AND Noncompliance Impulsive aggression Parent child interactions Social Interactions and peer acceptance Compliance CONCAN-1: Simultaneous Remission of ODD Symptoms Percentage of patients with remission of ODD sub-items of SNAP-IV OROS MPH IR MPH 70 Patients (%) 60 58% 50 40 30 35% 20 10 p=0.01 p=0.01 p=0.004 0 Week 4 Steele et al. APA 2005 Week 8 Endpoint Advantages of New Med Options Ease of compliance- once daily in AM! Not singled out to take meds at school! More reliable serum level through school/ business day and potentially into evening. Ongoing help with features of impulsivity, irritability, frustration and anger problems May reduce risk for associated syndromes (e.g. depression, anxiety and substance use disorder) Greatly reduced risk for diversion or abuse New Med Considerations Concerta vs Adderall XR vs Biphentin: -Some “do better”” on one family or other. -Sometimes shifting duration of action improves results or reduces side effects -Adderall XR, and Biphentin have more dose notches and can be “sprinkled” -Vyvanse dissolvable and long duration -Longer lasting & newer= more expensive -MPH Extended duration is not Concerta! Non-stimulant ADHD Meds Strattera: Approved (6 y. to adults) for ADHD -Overall a reduced effect size vs stimulants -Consider if poor stimulant response, and if anxiety or tics/Tourette’s Intuniv XR -approved for 6-12 years in Canada (teens approved in US and likely to come in Canada) as monotherapy or as a booster on top of stimulants for ADHD; also more continuous impact -has shown some impact for ODD symptoms -need to monitor cardiovascular and can be sedating. Both are “continuous” but pricey, no ODB coverage. Stimulant Side Effects Appetite reduction/ possible weight loss Insomnia GI upset Dry Mouth Headaches Slight increase in blood pressure and heart rate Dysphoria/suppressed mood/ irritability Hyperfocus or anxiety Increase in tics or pre-existent anxiety (50%) "ADHD in Adulthood: Assessment and Pharmacotherapy”, Craig Surman, Massachusetts General Hospital Adult ADHD Research Program, Harvard Medical School Stimulant Treatment is NOT Associated with an Increased Risk of Substance Abuse Percentage of subjects with a substance abuse disorder at 4-year follow-up Subjects with substance abuse disorder (%) 100% 80% 60% 40% 20% 0% Untreated ADHD (n=19) Biederman et al. Pediatrics 1999;104:e20 Medicated ADHD (n=56) Controls (n=137) Conclusions Many of the controversies about ADHD are a function of misinformation, lack of information, anecdotal stories or mental health stigma. ADHD is a real, often persisting and highly impactful condition. In fact, this is the best studies area of child mental health and it’s clear ADHD deserves active, multi-modal treatment! Not recognizing, assessing or treating ADHD may well have impacts and “side effects”. ADHD The End! Q&A