ADHD Treatment

CONTINUITY CLINIC Objectives Be familiar with the evidence supporting particular forms of management for ADHD, including medication Be familiar with the evidence supporting particular forms of management for ADHD, including medication Know the different classes of stimulant medications and their potential side effects Know the different classes of stimulant medications and their potential side effects Be familiar with Atomoxetine and its potential side effects Be familiar with Atomoxetine and its potential side effects

CONTINUITY CLINIC Recommendation 1: Management Program Primary care clinicians should establish a management program that recognizes ADHD as a chronic condition Primary care clinicians should establish a management program that recognizes ADHD as a chronic condition Strong evidence Strong evidence Strong recommendation Strong recommendation

CONTINUITY CLINIC Recommendation 1: Management Program Prevalence 4-12% of school-age children Prevalence 4-12% of school-age children 60-80% persist into adolescence 60-80% persist into adolescence Inform, educate, counsel, demystify Inform, educate, counsel, demystify family, child family, child Resources Resources local, national (CHADD, ADDA) local, national (CHADD, ADDA)

CONTINUITY CLINIC Recommendation 1: Management Program What distinguishes this condition from most other conditions managed by primary care clinicians is the important role that the educational system plays in the treatment and monitoring of children with ADHD. What distinguishes this condition from most other conditions managed by primary care clinicians is the important role that the educational system plays in the treatment and monitoring of children with ADHD.

CONTINUITY CLINIC Recommendation 2: Target Outcomes by Team The treating clinician, parents, and the child, in collaboration with school personnel, should specify appropriate target outcomes to guide management. The treating clinician, parents, and the child, in collaboration with school personnel, should specify appropriate target outcomes to guide management. Strong evidence Strong evidence Strong recommendation Strong recommendation

CONTINUITY CLINIC Recommendation 2: Outcomes- maximize function Relationships Relationships parents, siblings, peers parents, siblings, peers Disruptive behaviors Disruptive behaviors Academic performance Academic performance work volume, efficiency, completion, accuracy work volume, efficiency, completion, accuracy Individual Individual self-care, self-esteem self-care, self-esteem Safety in the community Safety in the community

CONTINUITY CLINIC Objectives of the Literature Review Effectiveness (short and long-term) and safety of therapies Effectiveness (short and long-term) and safety of therapies Medication and non-medication therapies Medication and non-medication therapies Single therapy vs combination Single therapy vs combination 6-12 year olds 6-12 year olds

CONTINUITY CLINIC Sources for Review Agency for Healthcare Research & Quality Agency for Healthcare Research & Quality McMaster Univ. Evidence-based Practice Center McMaster Univ. Evidence-based Practice Center Canadian Office for Health Technology Assessment Study (CCOHTA) Canadian Office for Health Technology Assessment Study (CCOHTA) Multimodal Treatment Study (MTA Study) Multimodal Treatment Study (MTA Study) Pelham et al. review of psychosocial therapies Pelham et al. review of psychosocial therapies

CONTINUITY CLINIC Recommendation 2: developing target outcomes Input Input parents, children (patient), teachers parents, children (patient), teachers 3-6 key targets 3-6 key targets realistic, attainable, measurable realistic, attainable, measurable methods will change over time methods will change over time

CONTINUITY CLINIC School Interventions Individual Education Plan 504 Plan School Interventions Individual Education Plan 504 Plan IDEA = Individuals with Disabilities Education Act IDEA = Individuals with Disabilities Education Act ADHD under “Other Health Impaired” ADHD under “Other Health Impaired” Educational Disability Educational Disability Services Services Section 504 of the Rehabilitation Act Section 504 of the Rehabilitation Act ADHD medical diagnosis ADHD medical diagnosis Medical Disability with educational impact Medical Disability with educational impact Accommodations Accommodations

CONTINUITY CLINIC Recommendation 3: make some recommendations The clinician should recommend stimulant medication and/or behavior therapy as appropriate, to improve target outcomes in children with ADHD The clinician should recommend stimulant medication and/or behavior therapy as appropriate, to improve target outcomes in children with ADHD Strong evidence (medication), Fair evidence (behavior therapy) Strong evidence (medication), Fair evidence (behavior therapy) Strong recommendation Strong recommendation

CONTINUITY CLINIC Recommendation 3: Efficacy of Stimulants Short-term benefits well established Short-term benefits well established Core symptoms: attention, hyperactivity, and impulsivity Core symptoms: attention, hyperactivity, and impulsivity observable social and classroom behaviors observable social and classroom behaviors IQ and achievement testing- less effect IQ and achievement testing- less effect

CONTINUITY CLINIC Recommendation 3: MTA Study Effects over 14 months Effects over 14 months 579 children years old 579 children years old 4 randomized groups 4 randomized groups medication alone medication alone medication and behavior management medication and behavior management behavior management behavior management standard community care standard community care

CONTINUITY CLINIC Recommendation 3: MTA Study Medication management alone Medication management alone Medication + behavior therapy Medication + behavior therapy > Community management > Community management > Behavior management alone > Behavior management alone

CONTINUITY CLINIC The Stimulants Nobody does it better The Stimulants Nobody does it better Short, intermediate (the “old” long-lasting), truly long acting Short, intermediate (the “old” long-lasting), truly long acting 22 studies show NO difference between methylphenidate, dextroamphetamine, or mixed amphetamine salts (Adderall) 22 studies show NO difference between methylphenidate, dextroamphetamine, or mixed amphetamine salts (Adderall) Individual’s response may vary Individual’s response may vary NO serologic, hematologic tests needed NO serologic, hematologic tests needed **EKG – based on history and risk

CONTINUITY CLINIC Non-stimulants Second rate-only 2 Non-stimulants Second rate-only 2 Tricyclic antidepressants Tricyclic antidepressants 9 studies alone 9 studies alone 4 studies =/< methylphenidate 4 studies =/< methylphenidate Bupropion (Wellbutrin, Zyban) Bupropion (Wellbutrin, Zyban) Clonidine Clonidine limited studies limited studies > placebo > placebo

CONTINUITY CLINIC Stimulants Dose determination Stimulants Dose determination NOT weight dependent NOT weight dependent Optimal effects with minimal side effects Optimal effects with minimal side effects nothing ventured, nothing gained nothing ventured, nothing gained Match target outcomes and timing Match target outcomes and timing crucial step prior to starting crucial step prior to starting

CONTINUITY CLINIC Stimulants Side effects Stimulants Side effects appetite suppression appetite suppression stomachache, headache stomachache, headache delayed sleep onset delayed sleep onset jitteriness jitteriness overfocused, dull demeanor overfocused, dull demeanor mood disturbances mood disturbances

CONTINUITY CLINIC Stimulants Side effects- NOT Stimulants Side effects- NOT seizures- NO increased frequency with mph seizures- NO increased frequency with mph growth delay- at least one negative study growth delay- at least one negative study Tourette syndrome Tourette syndrome 15-20% of patients have motor tics 15-20% of patients have motor tics 50% of TS have ADHD 50% of TS have ADHD 7 studies comparing stimulants vs placebo/other show NO increase in tics with stimulants 7 studies comparing stimulants vs placebo/other show NO increase in tics with stimulants

CONTINUITY CLINIC Short Intermediate Extended 3-4 hours 5-6 hours8-10 (12)hours

CONTINUITY CLINIC

AtomoxetineStrattera AtomoxetineStrattera Selective norepinephrine uptake inhibitor Selective norepinephrine uptake inhibitor Little effect on dopamine or serotonin uptake Little effect on dopamine or serotonin uptake Little effect on Ach, H1, alpha-2, DA receptors Little effect on Ach, H1, alpha-2, DA receptors Well-tolerated in adult and pediatric studies Well-tolerated in adult and pediatric studies

CONTINUITY CLINIC Atomoxetine...Randomized, Placebo- Controlled, Dose-Response children and adolescents 297 children and adolescents 8-18 years old; 71 % male 8-18 years old; 71 % male 70% had prior stimulant therapy 70% had prior stimulant therapy Combined/Inattentive/Hyper-impulsive Combined/Inattentive/Hyper-impulsive 63/33/2 % 63/33/2 % 37 % Oppositional-defiant disorder 37 % Oppositional-defiant disorder 1 depression, 1 anxiety disorder 1 depression, 1 anxiety disorder Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

CONTINUITY CLINIC Side Effects Side Effects Small samples: Small samples: dizziness 9% vs 1% placebo dizziness 9% vs 1% placebo vomiting 6% vs 7% vomiting 6% vs 7% Weight loss dose dependent Weight loss dose dependent mean 0.4kg at 1.2 mg/kg/d mean 0.4kg at 1.2 mg/kg/d small pulse, BP changes small pulse, BP changes no EKG changes no EKG changes <5% dropout rate atmx and placebo <5% dropout rate atmx and placebo Atomoxetine…AD/HD…Study. Pediatrics 108:e83, 2001

CONTINUITY CLINIC Efficacy of Atomoxetine vs Placebo in School-Age Girls with AD/HD Efficacy of Atomoxetine vs Placebo in School-Age Girls with AD/HD 52 children and adolescents 52 children and adolescents 7-13 years old 7-13 years old Combined/Inattentive/Hyper-impulsive Combined/Inattentive/Hyper-impulsive 79/21/0 % 79/21/0 % 38.5 % Oppositional-defiant disorder 38.5 % Oppositional-defiant disorder 13.5% phobias 13.5% phobias Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

CONTINUITY CLINIC Measures Measures ADHD Rating Scale- Parent ADHD Rating Scale- Parent Conners’ Parent RS-Revised Conners’ Parent RS-Revised No Teacher ratings No Teacher ratings Clinical Global Impressions of ADHD Severity- Clinician Clinical Global Impressions of ADHD Severity- Clinician Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

CONTINUITY CLINIC Side Effects Small sample size subset here (279 total); so no significant differences Small sample size subset here (279 total); so no significant differences Vomiting 19% vs 0% Vomiting 19% vs 0% Abdominal pain 29% vs 14% Abdominal pain 29% vs 14% Nausea 6.5% vs 14% Nausea 6.5% vs 14% ?Weight, cardiac... ?Weight, cardiac... Increased cough 16% vs 4.8% Increased cough 16% vs 4.8% Efficacy…Girls...AD/HD. Pediatrics 110:e75, 2002

CONTINUITY CLINIC Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial 228 children and adolescents 228 children and adolescents 184 atomoxetine, 44 mph; 10 weeks 184 atomoxetine, 44 mph; 10 weeks 7-15 year old boys; 7-9 year old girls 7-15 year old boys; 7-9 year old girls Most/all had prior stimulant therapy Most/all had prior stimulant therapy Combined/Inattentive/Hyper-impulsive Combined/Inattentive/Hyper-impulsive 76/23/1 % 76/23/1 % 53% ODD, 7% major depression 53% ODD, 7% major depression Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

CONTINUITY CLINIC Measures Measures ADHD Rating Scale- Parent Completed ADHD Rating Scale- Parent Completed ADHD Rating Scale- Parent Interview ADHD Rating Scale- Parent Interview Conners’ Parent RS-Revised Conners’ Parent RS-Revised No Teacher ratings No Teacher ratings Clinical Global Impressions of ADHD Severity- Clinician Clinical Global Impressions of ADHD Severity- Clinician Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

CONTINUITY CLINIC Findings Findings Comparable improvement between the two Comparable improvement between the two mean dose 1.4 mg/kg/d extensive mtb, 0.5mg/kg/d slow mtb mean dose 1.4 mg/kg/d extensive mtb, 0.5mg/kg/d slow mtb mph 0.85 mg/kg/d, (31mg/d) mph 0.85 mg/kg/d, (31mg/d) High rate of dropouts High rate of dropouts Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

CONTINUITY CLINIC Findings 43% of mph, 36 % atmx dropped out! 43% of mph, 36 % atmx dropped out! 11%; 5 % because of adverse effects comparable 11%; 5 % because of adverse effects comparable atomoxetine wt loss avg 0.6 kg; (mph 0.1) atomoxetine wt loss avg 0.6 kg; (mph 0.1) small changes both in pulse, BP small changes both in pulse, BP EKG, labs no problems, no differences EKG, labs no problems, no differences Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

CONTINUITY CLINIC Side Effects Generally comparable Generally comparable Vomiting 12% vs 0% Vomiting 12% vs 0% Abdominal pain 23% vs 17.5% (NS) Abdominal pain 23% vs 17.5% (NS) Nausea 10% vs 5% (NS) Nausea 10% vs 5% (NS) ?Weight, cardiac... ?Weight, cardiac... Cough 5% same Cough 5% same “Thinking abnormal” 0% vs 5% (N=2) “Thinking abnormal” 0% vs 5% (N=2) Atomoxetine and Methylphenidate... Prospective Randomized, Open-Label Trial JAACAP 41:7, 2002

CONTINUITY CLINIC Pros and Cons No abuse potential No abuse potential adolescent usage adolescent usage adult usage adult usage 24/7 coverage 24/7 coverage No tic relationship No tic relationship Novel class of med Novel class of med use with stimulants, too use with stimulants, too Little data head to head vs stimulants Little data head to head vs stimulants Weight loss/vomiting Weight loss/vomiting Takes week(s) to effects Takes week(s) to effects Tolerance Tolerance “starter kit” issue “starter kit” issue adjust if SSRI added adjust if SSRI added Cost Cost

CONTINUITY CLINIC Behavior Therapy accept no substitutes Behavior therapy Behavior therapy Emotions-based therapy Emotions-based therapy e.g. play therapy-NOT efficacious in ADHD e.g. play therapy-NOT efficacious in ADHD Thought patterns directed Thought patterns directed cognitive, cognitive-behavioral therapy cognitive, cognitive-behavioral therapy NOT efficacious in ADHD NOT efficacious in ADHD

CONTINUITY CLINIC Behavior Therapy Parent Training 8-12 weeks with trained therapist 8-12 weeks with trained therapist teaches parent skills teaches parent skills incorporates maintenance and relapses incorporates maintenance and relapses improves child’s functioning and behavior improves child’s functioning and behavior not necessarily achieves normal behavior not necessarily achieves normal behavior

CONTINUITY CLINIC Behavior Therapy Examples of Techniques Positive reinforcement Positive reinforcement reward for performance reward for performance Time-out Time-out removing positive reinforcement removing positive reinforcement Response cost Response cost losing advance rewards losing advance rewards Token economy Token economy combination combination

CONTINUITY CLINIC Behavior Therapy Meta-analyses difficult and few Must be maintained to be effective Must be maintained to be effective Stimulant effects much > behavioral therapy Stimulant effects much > behavioral therapy MTA study: combination > med alone, but not a statistically significant difference MTA study: combination > med alone, but not a statistically significant difference However, parents and teachers more satisfied However, parents and teachers more satisfied Schools can implement Schools can implement 504 Plan 504 Plan IEP IEP

CONTINUITY CLINIC Recommendation 4: When to re-evaluate When the selected management for a child with ADHD has not met target outcomes, clinicians should evaluate the original diagnosis, use of all appropriate treatments, adherence to the treatment plan, and presence of coexisting conditions When the selected management for a child with ADHD has not met target outcomes, clinicians should evaluate the original diagnosis, use of all appropriate treatments, adherence to the treatment plan, and presence of coexisting conditions Weak evidence Weak evidence Strong recommendation Strong recommendation

CONTINUITY CLINIC Recommendation 4: Ddx in re-evaluation unrealistic target symptoms unrealistic target symptoms poor information regarding child’s behavior poor information regarding child’s behavior incorrect diagnosis and/or incorrect diagnosis and/or coexisting condition interfering coexisting condition interfering ODD, conduct disorder, mood, anxiety, LD ODD, conduct disorder, mood, anxiety, LD poor adherence/compliance poor adherence/compliance treatment failure treatment failure

CONTINUITY CLINIC Recommendation 4: Steps in re-evaluation Re-establish target symptoms Re-establish target symptoms “team” communication “team” communication Gather further information, other sources Gather further information, other sources Consider consultation Consider consultation Consider psycho-educational testing Consider psycho-educational testing

CONTINUITY CLINIC Recommendation 4: True treatment failure Lack of response to 2-3 stimulants Lack of response to 2-3 stimulants maximum dose without side effects maximum dose without side effects any dose with intolerable side effects any dose with intolerable side effects Inability to control child’s behavior Inability to control child’s behavior Interference of coexisting condition Interference of coexisting condition Refer to mental health Refer to mental health

CONTINUITY CLINIC Recommendation 5: follow-up guidelines The clinician should periodically provide a systematic follow-up for the child with ADHD. Monitoring should be directed to target outcomes and adverse effects by obtaining specific information from parents, teachers, and the child. The clinician should periodically provide a systematic follow-up for the child with ADHD. Monitoring should be directed to target outcomes and adverse effects by obtaining specific information from parents, teachers, and the child. Fair evidence Fair evidence Strong recommendation Strong recommendation

CONTINUITY CLINIC Recommendation 5: follow-up guidelines Team management plan Team management plan not just : “What does the doctor recommend?” not just : “What does the doctor recommend?” Recording clinical data Recording clinical data flow sheet, progress note flow sheet, progress note Interview, T-Con, teacher reports, report cards, checklists Interview, T-Con, teacher reports, report cards, checklists

CONTINUITY CLINIC Recommendation 5: frequency of follow-up NO controlled trials document the appropriate frequency NO controlled trials document the appropriate frequency MTA study: more frequent did better, BUT MTA study: more frequent did better, BUT Once stable, visit every 3-6 months Once stable, visit every 3-6 months

CONTINUITY CLINIC Conclusion nuggets Conclusion nuggets ADHD is a chronic condition ADHD is a chronic condition Explicit negotiations regarding target outcomes are key Explicit negotiations regarding target outcomes are key Stimulant and behavior therapy use are the mainstay of therapy Stimulant and behavior therapy use are the mainstay of therapy