Pharmacological Management of ADHD and Associated Comorbidities

1. Pharmacological Management of ADHD and Associated Comorbidities Regina Bussing, M.D., M.S.H.S. Professor, Division of Child and Adolescent Psychiatry

2. ADHD: Etiology and Prevalence Etiology • No single cause • Many possible etiologies • Genetic causation increasingly implicated Prevalence • Estimates in school-age children: 3% to 9% • More commonly diagnosed in boys (4:1 to 9:1) • Girls were under-represented in clinical populations, but increasing numbers of girls receiving ADHD treatment • More prevalent in 1st degree biologic relatives Ref: Greenhill 1993; Biederman 1989; Safer 1988; Lambert 1981

3. National Survey of Children's Health, 2003: Attention-Deficit/Hyperactivity Disorder Percent of Youth (4-17y) ever diagnosed and currently medicated Percent of Youth (4-17y) ever diagnosed Source: http://www.cdc.gov/ncbddd/adhd/default.htm

4. ADHD: Core Symptoms Varying degrees of: • Inattention • Hyperactivity • Impulsivity Symptoms also vary in: • Degree of impairment • Frequency of occurrence • Pervasiveness Ref: Greenhill 1993; Swanson 1992; Cantwell 1985

5. DSM-IV ADHD Criteria:Inattention Symptoms Behaviors manifested often: • Careless mistakes • Difficulty sustaining attention • Seems not to listen • Fails to finish tasks • Difficulty organizing • Avoids tasks requiring sustained attention • Loses things • Easily distracted • Forgetful Ref: APA 1994

6. DSM-IV ADHD Criteria:Hyperactivity/Impulsivity Symptoms Hyperactivity behaviors manifested often: • Difficulty engaging in leisure activities quietly • Fidgeting • Unable to stay seated • Moving excessively (restlessness) • “On the go” • Talking excessively Impulsivity behaviors manifested often: • Blurting out answer before question is completed • Difficulty waiting turn • Interrupting/intruding upon others Ref: APA 1994

7. ADHD: DSM-IV General Criteria and Subtypes Inattention and hyperactivity-impulsivity symptoms: • Onset before age 7 • Present for > 6 months • Present in  2 settings (e.g., home, school, work) Subtypes: • AD/HD, combined type: criteria from both dimensions • 6 of 9 from both symptom lists • AD/HD, predominantly inattentive type: inattentive criteria • 6 of 9 inattentive symptoms • AD/HD, predominantly hyperactive-impulsive type: hyperactive-impulsive criteria • 6 of 9 hyperactive-impulsive symptoms Ref: APA 1994

8. ADHD: Context for Pharmacological Treatment - Overview of Assessment Process • What is the child’s developmental level? • Does the child meet criteria for ADHD? • What are the areas of functional impairment? • What comorbidities are present? • What is family history of mental disorders? • What are the strengths of the child, family, school setting and social environment? • What treatment plan is indicated?

9. ADHD: Patient Evaluation Procedures • Parent/child interviews • Parent-child observation • Behavior rating scales • Physical examination (including neurologic) • Cognitive testing (as indicated) • Other studies • Check on audiology/vision testing • Laboratory studies are not pathognomonic Ref: Reiff 1993

10. Differential diagnosis and possible comorbidities of childhood ADHD Ref: Reiff 1993; Barkley 1990

11. ADHD: Comorbidities in Children/Adolescents • Learning disorders • Language and communication disorders • Oppositional defiant disorder • Conduct disorders • Anxiety disorders • Mood disorders • Tourette’s syndrome; chronic tics Ref: Biederman 1991; Hinshaw 1987

12. Historical Context 1998 NIH Consensus Conference 2000 -2005 Concerta, Metadate CD, Ritalin LA, Strattera, Focalin XR 1937 Amphetamine reduces disruptive behavior Period of Increasing Access and Medication Use: 1987–96 Medicaid/HMO prescription studies 1989–99 NAMCS studies 1987-97 NMES/MEPS studies 1956 Ritalin introduced 1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2011 DSM-IV 1994 AD/HD Post-encephalitic Behavior Disorder DSM-III 1980 ADD/+-Hyper Minimal Brain Dysfunction 1902 G. F. Still “Defect in Moral Control” Period of “Use Attenuation”: 1997-02 MEPS 2001-04 NHANES 2003 NCHS 2006 NHIS DSM-II 1968 Hyperkinetic Reaction of Childhood

13. MMWR, September 2, 2005 / 54(34);842-847 United States 2003 (NCHS) Reflects variations in prevalence, parental help seeking, provider practice patterns and other factors

16. ADHDPharmacotherapy Stimulants • Methylphenidate-based • Dextroamphetamine-based • Mixed Amphetamine Salts Non-Stimulant • Atomoxetine Other (Off-label, but with EB) • Antidepressants • Antihypertensives

17. Long-Acting Stimulant Agents

18. Begin ADHD algorithm

20. ADHD and Other Disruptive Disorders • ODD • Diagnosis: • Similar age of onset, course • Likely the most frequent comorbidity encountered • Prompts specialty mental health referral (over-represented) • Treatment implications • Family and patient education • Raises caregiver stress more than ADHD or CD • Psychotherapy choices (PCIT; parenting interventions) • Medication implications (stimulants; non-stimulant ADHD treatments; alpha agonists)

21. ADHD and Other Disruptive Disorders • CD • Diagnosis: • Variations in age of onset, course • Comorbidity with significant prognostic impact (increased risk of drug abuse; antisocial behaviors) • Treatment implications • Family likely has significant other risk factors • Psychotherapy choices (PCIT; parenting interventions; MST) • Medication implications (stimulants; non-stimulant ADHD treatments; atypical neuroleptics; possibly mood stabilizers for anti-aggressive effects)

22. ADHD and Anxiety Disorders • GAD and SAD • Diagnosis: • Tease out age of onset and course of symptoms • “Shared” symptoms (inattention, hyperactivity; academic performance problems; sleep problems) • Unique features (worry; fears; significant somatic complaints) • Treatment implications • Families may be reinforcing avoidances and fears • Psychotherapy choices (CBT) • Medication implications (stimulants; non-stimulant ADHD treatments; antidepressant options)

23. ADHD and Anxiety Disorders • PTSD • Diagnosis: • Identify stressor event • Tease out age of onset and course of symptoms • “Shared” symptoms (inattention, hyperactivity; academic performance problems; sleep problems) • Treatment implications • Families often have significant other stressors • Psychotherapy choices • Medication implications (stimulants; non-stimulant ADHD treatments; antidepressant options)

24. ADHD and Mood Disorders • Major Depression/Dysthymia • Diagnosis: • Differentiate age of onset, course • “Shared” symptoms (inattention, academic performance problems; sleep problems) • Treatment implications • Family and patient education • Psychotherapy choices (CBT; IPT; DBT) • Medication implications (stimulants; non-stimulant ADHD treatments; antidepressant options)

25. ADHD and Mood Disorders • Bipolar Disorder • Diagnosis: • Differentiate age of onset, course (issues of mixed presentation and of rapid cycling) • “Shared” symptoms (attention problems; hyperactivity; increased speech output; loud; sleep problems; academic performance problems) • Unique symptoms (grandiosity; psychotic symptoms; severe mood lability; severe aggression) • Treatment implications • Family and patient education • Medication implications (mood stabilizers; atypical neuroleptic medications; issue of stimulants; non-stimulant ADHD treatments; antidepressant options)

26. ADHD and Tic Disorders • Chronic Tics or Tourette’s Disorder • Onset of ADHD often precedes onset of Tics or TS • Important to inquire about family history and educate parents about stimulants and tics/TS • Treatment • Stimulants were considered “contraindicated” in past • Focus now on improving functioning – ADHD may be more impairing than tics • Complex regimens may be used, combining ADHD medications with alpha-agonists and/or atypical neuroleptic medications

27. Case Example • Bob presented to child psychiatrist for ADHD, SLD, expressive language disorder • Family history + ADHD, depression • Treated with stimulants, school interventions as preadolescent • Developed severe aggression, mood instability, some seasonal variations in mood in early adolescence • Repeated inpatient crisis stabilization, family therapy, medication adjustments • Developed psychotic symptoms with hypomanic component • Residential treatment pursued

28. Bob follow-up • Temporarily stopped ADHD medication treatment, used antipsychotic medications • Moved into mood stabilization, resumed ADHD medications once Bob had remained free of psychotic symptoms for 3 months • Continued family intervention (“the explosive child”) • Able to resume regular school attendance, with partial special education services, continued ADHD treatment, ongoing mood stabilization, off all antipsychotic medications • Continued to experience social isolation, but markedly improved overall functioning • Young adult outcome: subclinical ADHD symptoms without further mood disturbance; completed high school; dropped out of community college; works successfully as cook; terminated outpatient therapy and medication therapy age 22.

29. Questions/Discussion