2013 Virtual AD/HD Conference 1

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1 Medication for ADHD & Coexisting Conditions Dr. Kenny Handelman Child, Adolescent & Adult Psychiatrist Halton Healthcare Adjunct Professor of Psychiatry, University of Western Ontario Overview: Overview of ADHD Symptoms Treatment Treatment Targets First Line Medications Stimulants Non-stimulants Treatment Algorithms Second/Third Line Medications Treating ADHD with Coexisting (comorbid) Conditions Estimated ADHD Sufferers in Canada in 2005 ADHD in the Spectrum of Psychiatric Disease 12 month prevalence data (N = 3,199) ADHD in children, teens (age 5 19 years) ADHD in adults (age years) Total population 6,182,933 18,567,976 Prevalence [%] 6% 4% Patients with ADHD 370, ,719 % diagnosed 33% 7% Patients persisting 122,422 51, % 7.00% 6.00% 5.00% 4.00% 3.00% 2.00% 1.00% 0.00% MDD Social Phobias SUD ADHD PTSD Panic Disorder Bipolar Disorder Kessler RC et al. Am J Psychiatry. 2006;163(4): Statistics Canada, 2004 projected to 2005; % diagnosed calculated based on estimate of treated patients in Canada Kessler RC, et al. Am J Psych Why Treat Adult ADHD? Interpersonal problems / family conflict times more motor vehicle crashes 2-3 ~ 75% of associated psychopathologies times greater risk for depression 3 times greater risk for substance abuse School difficulties: 35% drop-out rate 5 Employment-related problems: 6 Miss an average of 13 days of work per year productivity Lower occupational status Legal difficulties 7 Two Major Etiologies of ADHD Genetic (80%) Environmental (20%) Fetal distress (e.g., preterm birth) 2 Lifestyle risks (e.g., smoking, drinking alcohol, drug use during pregnancy) 3 Traumatic head injury 4 1. Weiss M, et al. J Psychiatr Pract. 2002;8(2): Barkley RA, et al. J Int Neuropsychol Soc. 2002;8(5): Barkley RA, et al. Pediatrics. 1996;98(6 Pt 1): Kessler RC, et al. Am J Psychiatry. 2006;163(4): Barkley RA. J Clin Psychiatry. 2002;63(Suppl 12): Kessler RC, et al. J Occup Environ Med. 2005;47(6): Biederman J, et al. J Clin Psychiatry. 2006;67(4): Faraone SV, et al. Biol Psychiatry. 2005;57(11): Mick E, et al. J Dev Behav Pediatr. 2002;23(1): Mick E, et al. J Am Acad Child Adolesc Psychiatry. 2002;41(4): Max JE, et al. Dev Neuropsychol. 2004;25(1-2): Virtual AD/HD Conference 1

2 Cerebral Glucose Metabolism in Adults with Hyperactivity of Childhood Onset Anterior Cingulate Dysfunction in ADHD fmri and the Counting Stroop Global and regional glucose metabolism by PET scan reduced in adults who have been hyperactive since childhood Normal Bush et al Largest reductions in: Premotor cortex Superior prefrontal cortex With ADHD Zametkin AJ, et al. N Engl J Med. 1990;323(20): Medical Mentorship 2007 Activation Disorder of the Cognitive Division of the Anterior Cingulate Cortex with ADHD Reversed with Methylphenidate Bush G et al. Arch Gen Psychiatry. 2008:65: OROS MPH Placebo Baseline 6 Weeks p = 0.02 vs PBO Functional magnetic resonance imaging: base level and 6 weeks Osmotic-controlled release oral system methylphenidate group shows activation of damcc region at 6 weeks vs. PBO n = 21 adults with ADHD; dose up to 1.3 mg/kg/day OROS MPH or placebo Heritability Coefficient 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, ADHD Mean 1 Average genetic contribution based on twin studies Faraone SV. J Am Acad Child Adolesc Psychiatry 2000;39: Hemminki K, Mutanen P. Mutat Res. 2001;25: Palmer LJ, et al. Eur Resp J 2001;17: ADHD Presentations ADHD Inattentive Presentation Formerly called ADD ADHD Hyperactive Impulsive Presentation ADHD Combined Presentation ADHD Types: Childhood vs. Adulthood Inattentive Type 22% 53% Inattentive Type Combined Type 78% 47% Combined Type In Childhood In Adulthood McGough, Smalley, McCracken et al. American Journal of Psychiatry. September 2005, Vol. 162, Page Virtual AD/HD Conference 2

3 Inattention: Pediatric to Adult Symptom Migration Hyperactivity: Pediatric to Adult Symptom Migration Childhood DSM-IV-TR symptoms 1 Difficulty sustaining attention Does not listen Difficulty following instructions Cannot organize Loses things Easily distracted/forgetful Common adult symptoms 2 Difficulty sustaining attention to reading or paperwork Easily distracted and forgetful Poor concentration Poor time management Difficulty finishing tasks Misplaces things Childhood DSM-IV-TR symptoms 1 Squirms and fidgets Runs or climbs excessively Cannot play or work quietly On the go, driven by a motor Talks excessively Common adult symptoms 2 Inner restlessness Overwhelmed Self-selects active jobs Talks excessively Fidgets when seated 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition, text revision. Washington, DC: American Psychiatric Press, Adler L, Cohen J. Psychiatr Clin N Am. 2004;27: American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition, text revision. Washington, DC: American Psychiatric Press, Adler L, Cohen J. Psychiatr Clin N Am. 2004;27: Impulsivity: Pediatric to Adult Symptom Migration Childhood DSM-IV-TR symptoms 1 Blurts out answers Cannot wait his or her turn Intrudes on or interrupts others Common adult symptoms 2 Impulsive job changes Drives too fast, has traffic accidents Irritability or quickness to anger 1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th edition, text revision. Washington, DC: American Psychiatric Press, Adler L, Cohen J. Psychiatr Clin N Am. 2004;27: Executive Functions: Executive Functions Definition: EF s refer to higher-order cognitive processes that underlie selfregulation and goal directed behaviour Including: Working Memory Response Inhibition Set Shifting Abstraction Planning Organization Fluency Certain Aspects of Attention Doyle, A (2006) J Clin Psychiatry: Executive Functions in ADHD A Conflicting Viewpoint: Dr. Thomas Brown describes ADHD as a developmental disorder of Executive Functioning He acknowledges that neuropsychological tests only identify approximately 30% of people with ADHD having measurable EF deficits He writes: A person s ability to perform the complex, self managed tasks of everyday life provides a much better measure of his or her executive functioning than can neuropsychological tests By this definition, all individuals with ADHD have EF difficulties... Interview with Dr. Brown on my Podcast: Multimodal Treatment of Adult ADHD ADHD medications: Stimulants Non-stimulants Psycho-education Treatment of comorbid conditions Therapy (individual, marital, social skills, Cognitive Behavior Therapy (CBT)) Appropriate educational/vocational plan Appropriate physical and special interest activities Coaching Brown (2006) Int J of Disability, Development and Education: EF and ADHD Implications of Two Conflicting Views 2013 Virtual AD/HD Conference 3

4 How To Decide Whether to Use ADD Medications: Balancing Risk : Benefit Ratio Using Impairment as a deciding factor What is First Line? Medication which is approved for a condition, and is often used first First Line vs. First Choice i.e. Atomoxetine How doctors decide which medication to use first Factors include: Clinical trials FDA approval Published clinical guidelines Expert consensus guidelines/opinions Colleagues experiences Doctor s own patients s experiences Patient preference Patient family member s experiences How Well Do ADHD Medications work for Adults with ADHD? Seemingly not as well as they do in children/teens with ADHD Medication responders often only show a 50% reduction of core ADHD symptoms (worse response than in children) (Safren 2005: Mastering Your Adult ADHD; Oxford University Press) Medication response may be variable: Some people may have a robust response i.e % symptom reduction Many people have a response i.e % response i.e. not complete, but measurable and important Treatment Targets: What are you aiming for? ADHD symptom reduction? Improvement in Functioning? Improvement in Quality of Life? How do you know when you get there? i.e. when is treatment successful? Responses to ADHD Mediction: 1. A great clinical response 2. Insufficient response from medication (or a partial response ) 3. Poor/no response ** Be careful not to miss a partial response because there is a measurable response, but it s not good enough **How do you identify a partial clinical response? Assess it, measure it! (use ASRS or similar tool) How To Think About Medication for ADD/ADHD: Methylphenidate Ritalin Ritalin SR Methylin Concerta Ritalin LA Metadate CD Biphentin Focalin/Focalin XR Daytrana Amphetamine Medications Dexedrine/Dexedrine Spansules Adderall/Adderall XR Vyvanse Non Stimulant Strattera (Atomoxetine) Intuniv (Guanfacine XR) Kapvay (Clonidine XR) 2013 Virtual AD/HD Conference 4

5 Sample ADHD Medications Duration of Action: Ritalin 4 hrs Adderall 4-6 hrs Ritalin LA Metadate CD Biphentin Concerta Adderall XR Vyvanse Strattera Intuniv/Kapvay 8 hrs 8 hrs 10 hrs 12 hrs 12 hrs 14 hrs 24 hrs 24 hrs Benefits of stimulants Quick response Works when you take it no need to build up 80 % response rates Generally minimal side effects Common Side Effects of Stimulants Decreased appetite Insomnia Tics Mood/anxiety symptoms Agitation (? Growth Retardation) Affective Blunting Non-Stimulant: Atomoxetine (Strattera) Worth using Weight based dosing No suicidal ideation warning in adults Potential drug interactions Metabolized by CYP 2D6 so medicines which slow this enzyme will boost Strattera blood levels This list includes: Fluoxetine (Prozac), Paroxetine (Paxil), Buproprion (Wellbutrin), Quinidine (anti-arrythmic) and others read more here: Benefits: Does not worsen tics Not abusable May help anxiety May help with insomnia Works around the clock (early morning, late evening) 2013 Virtual AD/HD Conference 5

6 Non-Stimulant cont d Atomoxetine: Drawbacks: Not as effective as a stimulant for core ADHD symptoms Takes weeks to work (general 4-6 weeks, may need longer) Chance of sexual side effects (trouble with erections/delayed ejaculation) Chance of urinary retention (be careful with males 60 years old and up) CADDRA Canadian ADHD Practice Guidelines Third Edition, October 2011, Virtual AD/HD Conference 6

7 OROS MPH in Adult ADHD: Mean Change in CAARS Total Score Week 1 Week 3 Week 5 EP Vyvanse The first PRO-Drug for ADHD Improvement Mean Change from Baseline in CAARS Total Score * ** *** *** * *** ITT population=394 p<0.05; *p<0.01; **p<0.005; ***p<0.001 vs. placebo Medori et al. Biol Psych, 2008 Improvement LDX Demonstrated Significant Improvement in PERMP for Up to 14 Hours Postdose LS Mean Change in PERMP 7:00 AM 6:30 AM Dose First Test N=104. *p<.005 vs. placebo; p<.0001 vs. placebo. Data on file LDX 062, Shire US Inc. * Mean PERMP-C Change From Predose Measurement Time Postdose (Hours) LS = Method of Least Squares 9:00 PM Last Test Atomoxetine Efficacy at 10 Weeks Improvement Mean Change from Baseline * INV PT INV PT Study LYAA Study LYAO Investigator- and Patient-rated total ADHD Score Reductions on the CAARS 1,2 INV=Investigator-rated; PT=Patient-rated; CAARS=Conners' Adult ADHD Rating Scale 1. Michelson et al. Biol Psychiatry 2003;53(2): Simpson et al. Drugs 2004;64(2): Atomoxetine Placebo Atomoxetine patients started at 60 mg/day, then increased to 90 mg/day and 120 mg/day at weeks 2 and 4 respectively, as needed. *p=.005 p=.002 p=.002 p=.008 Atomoxetine Efficacy at 221 Weeks INV PT 0 ADDERALL XR Pulse Delivery System Improvement Mean Change from Baseline N= * N= * Investigator- and Patient-rated total ADHD Score Reductions on the CAARS INV=Investigator-rated; PT=Patient-rated; CAARS=Conners' Adult ADHD Rating Scale Atomoxetine mg/day *p<.001 Adler et al. J Atten Disord 2008;12(3): Virtual AD/HD Conference 7

8 Questions? This is the end of Section 1. After some questions, we will start the second part of the presentation Virtual AD/HD Conference 8