Disclosures. Syllabi/Slides for this program are a supplement to the live CME session and are not intended for other purposes.

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1 1:05-2:20pm ADD & ADHD in Children and Adults: Beyond Stimulants SPEAKER Daniel Press, MD ADD & ADHD in Children and Adults: Beyond Stimulants Daniel Press, M.D. Associate Professor in Neurology Beth Israel Deaconess Medical Center and Harvard Medical School Disclosures No relationship to pharmaceutical industry I may be mentioning off-label use of medications

2 Definition of ADHD A developmental disorder that begins in childhood Impairments in attention, either with or without hyperactivity and impulsivity These impairments cause clear problems in functioning DSM 5 Criteria Persistent inattention +/ hyperactivity that interferes with function and is not solely oppositional, defiant, hostile or due to failure to understand. Symptoms begin before age of 12 Present in two or more settings with clear evidence of a significant problem No other disorder (depression, thought disorder) to explain symptoms

3 Adult ADHD Like pediatric ADHD, it must begin in childhood Symptoms continue past adolescence, with problems in organization, vigilance, and distractibility Generally, hyperactivity abates but impulsivity can remain a problem Between 10 50% of childhood ADHD continues into adulthood Patient SP in kindergarten Epidemiology 3 5% of children are diagnosed with ADHD, making it the most common LD In childhood, boys outnumber girls by 2:1 for inattentive type and 4:1 for hyperactive type. Girls with inattentive type may have fewer behavioral problems, leading to underdiagnosis The percentage of children who remain symptomatic into adulthood ranges from 4% to 80% depending on the criteria used for diagnosis ADHD Does Not Exist Cultural bias to explain poor performance (Lake Wobegon effect) ADHD claims to make a disorder out of a personality trait, it is normal variance Medicalizing our deficits e.g. social phobia, alopecia, short stature Vastly different incidences across cultures, states, and even zip codes

4 ADHD Does Not Exist Starting school early because of a person s birthday increases diagnosis Difference in rate of ADHD per 10,000 children Rate of ADHD diagnosis by month of birth Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month of Birth Rate of ADHD diagnosis by month of birth States with Sept Cutoff States without Sept Cutoff ADHD Does Exist Difference in rate of ADHD per 10,000 children July vs Aug vs Sept vs July vs. Aug vs. Sept vs. Aug. Sept Oct Aug. Sept. Oct. Month of Birth Cultural demands do not negate a disorder (e.g. dyslexia) Normal variance can still cause disease (hypertension) Structural and functional imaging studies show differences in specific brain regions Family clustering suggests genetic role

5 SP Family Pedigree G. Bush et. al, Biol. Psychiatry 1999

6 Attentional Network Compromise position? DLPFC Lateral Surface Parietal Ant. Cingulate Medial Wall If attentional problems are symptomatic, and out of proportion to a personʼs intelligence, then it is at least reasonable to consider treatment. VLPFC Cereb ellum G. Bush Biol Psych 2011 Causes of ADHD Genes Heritability of % of phenotypic variance But known genes account for only 3% Unknown genes, genes with small effects, genegene interactions* Environment Mother who smoke during pregnancy 2x risk Patients with obesity and diabetes Maternal DM during pregnancy *Zuk O, PNAS 2012 Froehlich TE Pediatrics 2009 Differential Diagnosis Obstructive Sleep Apnea (ask about snoring, daytime sleepiness, naps, etc) Mood disorders both depression and hypomania can impair attention Previous closed head injury, focal lesions, toxic metabolic encephalopathies Seizure disorders (staring spells) Physical or sexual abuse

7 Differentiating ADD from Bipolar disorder ADHD Bipolar Time course Constant Episodic Sleep patterns Normal Markedly shortened Impulsivity Moderate Severe Comorbid Psychiatric Conditions Up to 75% of adult patients with ADHD have a comorbid psychiatric illness Other learning disorders (e.g. dyslexia) Mood disorders (Odds ratio 2.7 to 7.5) Substance Abuse (OR 1.5 to 7.9) Intermittent Explosive Disorder (OR 3.7) Kessler et. al, Am J Psych 2006 Overlapping conditions Comorbid Conditions: Treatment Implications Anxiety + Depression Attention Deficit Disorder Oppositional Behavior + Conduct Disorder Depression: Approximately 15 30% of patients who present with ADHD have comorbid depression Activating antidepressants can help both conditions: Bupropion (wellbutrin) Atomoxetine (strattera) Venlafaxine (effexor) Internalizing Disorders Externalizing Disorders Feldman and Reiff NEJM 2014

8 Comorbid Conditions: Treatment Implications II Bipolar Disorder Stimulants can precipitate mania. Either use a concomitant mood stabilizing medication or use an activating antidepressant medication (bupropion). Substance Abuse 25 45% comorbidity, especially with anti social personality. Early treatment may prevent substance abuse. Once present, avoid stimulants. Comorbid Conditions: Treatment Implications III Comorbid learning disabilities 20 30% of children with ADHD have reading problems (dyslexia) or arithmetic problems. Reading skills improve with stimulant medication in ADHD + dyslexia children, but not children with dyslexia alone. Tests of Attention MoCA Test Vigilance/Sustained Attention Continuous Performance Tasks Divided Attention Trails B, Stroop Color Interference Working Memory Digit Span Backwards, Verbal Fluency Response Inhibition Motor Go No Go

9 Neuropsychological Testing Definitive for diagnosis, but expensive ($2000 $3000) Useful when diagnosis is uncertain (bipolar vs. ADD) Useful when comorbid learning issues may be present (dyslexia) Accommodations for standardized tests Behavioral strategies Pharmacological strategies Therapy Behavioral Strategies in ADHD 1. Children Effective therapies include Teaching children how to communicate emotions Promote positive parent child interaction skills Practicing behavioral modification techniques (rewarding positive behaviors) Behavioral classroom management Positive reinforcement drives behavior, negative reinforcement doesn t work Feldman and Reiff NEJM 2014 Behavioral Strategies in ADHD 2. Adults Impose organizational tools PDAs/ A single organizer/calendar A single To Do list Limit distractions Do only one task at a time, donʼt switch Limit outside noise Consider a personal coach

10 Behavioral Strategies and School Consider neuropsychological testing to confirm diagnosis and determine whether untimed tests, testing in quiet environment, and other accommodations are indicated Behavioral strategies Pharmacological strategies Therapy Pharmacotherapy of ADHD Stimulant Medications Ritalin (methylphenidate) Adderall (mixed salt of dextroamphetamine) Activating antidepressants (Not SSRIs) Tricyclic antidepressants Wellbutrin (bupropion) Other agents Strattera (atomoxetine) norepinephrine reuptake inhibitor Provigil (modafanil) wake promoting agent Stimulant Medications Between 50 80% of subjects will have a good response Relatively contraindicated in people with substance abuse history, especially if abuse is an active issue Illicit use of these drugs is growing, particularly in schools and colleges

11 Side effects of Stimulant Medications Cardiovascular side effects with average of 3 5mm increase in BP, and slight increase in heart rate (5 BPM) otwo retrospective studies looked for cardiac events oone with 150,000 treated with amph, met or atom found no association osecond with 44,000 treated with met vs. nonusers found 1.8 fold increase in sudden death but no dose response and may not be causal Side effects of Stimulant Medications II Anorexia Insomnia Potential for abuse (but also potential to prevent substance abuse) Stimulants Non Stimulants Farone and Glatt J Clin Psych 2010 Farone and Glatt J Clin Psych 2010

12 Overall Efficacy of Stimulant and Non stimulant Medications Short Acting Stimulants 0.96 Cohen D effect size Long Acting Stimulants 0.73 Non Stimulants 0.39 Stimulants > Non Stimulants No significant difference between short and long acting No significant difference between methylphenidate and dextroamphetamine Farone and Glatt J Clin Psych 2010 Drug: Short-acting racemic mixture Intermediate duration Long duration Stereoisomer/ prodrug Methylphenidate Ritalin, methylin (3-4 hrs) 5-10mg bid Ritalin SR (4-7 hrs) 20mg qam (to bid) Concerta, Ritalin LA, Metadate CD, Daytrana patch (8-12 hr) 30-60mg qam Focalin (dmethylphenidate) and Focalin XR (50% dose) Dextroamphetamine Dexedrine (4-5 hrs) 5mg bid Adderall (mixed salt, 4-7 hrs) 10-20mg qam-bid Adderall XR (8-10 hrs) 20-40mg qam Prodrug:Vyvanse 30mg qam Atomoxetine (Strattera) Norepinephrine reuptake inhibitor, somewhat similar to venlafaxine Not habit forming particularly useful in patients with substance abuse concern Has antidepressant properties May not be as effective as stimulants Women of Childbearing Years Should be discussed regularly Goal is to have a plan ahead of time as to whether medication can be tapered Risks are present but low, along with risk of coming off medication if attention symptoms are severe

13 Controversies: Cosmetic Neurology Some are using these medications even in absence of identified disorder Ethics are murky Stimulant use on college campuses as study aid Talk with patients to minimize risk Executive Function poor ideal Executive Function Paradigm Normal function inhibition Set-shifting On task Creativity low intermediate high Dopamine Levels Executive function and Attention clinic 52 New patients Neurological disease? NO Comorbidities? NO NEUROPSYCH TESTING YES (15%) YES (25%) MRI Toxic/Metabolic/Infection EEG LP Psychiatry/ Sleep Resources ADHD in children and adolescents Feldman and Reiff NEJM 2014 ADHD in Adults Volkow and Swanson NEJM 2013 Vanderbilt Assessment Scales for parents and teachers Adult ADHD Self report scale (ASRS) 5_Guidelines.pdf Brainfit club training Prescription medication?tms/tdcs

14 Conclusions ADHD in children and adults is controversial, but the cardinal symptoms are amenable to therapy Differential diagnosis includes medical (OSA) and psychiatric conditions (BPD) Hallmark of therapy is stimulant medication, but behavioral therapies are also effective, particularly in conjunction with medications Precautions need to be exercised in at risk individuals, where newer agents may be safer ASK QUESTIONS USING OUR NEW SOCIAL Q&A FEATURE! Navigate to Click a Session Ask a Question Up-Vote a Question