ADHD Diagnosis

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ADHD Diagnosis Treatment

• Presented by
• James E. Greer, M.D.

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Definition

• The essential feature of Attention
  Deficit/Hyperactivity Disorder is a persistent
  pattern of inattention and/or hyperactivity-impuls
  ivity that is more frequent and severe than is
  typically observed in individuals at a comparable
  level of development
• (DSM-IV-1994)

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Subtypes of ADHD

• ADHD, Combined Type gt6 Inattentive gt6
  Hyperactive Impulsive symptoms present
• ADHD, Predominantly Inattentive Type- gt6
  Inattentive, lt6 Hyperactive/Impulsive
• ADHD, Predominantly Hyperactive Impulsive Type-
  gt6 Hyperactive/Impulsive,lt6 Inattentive

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Diagnostic Criteria

• Inattentive Symptoms
• Fails to give close attention to details or makes
  careless mistakes
• Has difficulty in sustaining attention in tasks
  or play activity
• Does not seem to listen when spoken to directly
• Does not follow through on instructions/does not
  complete schoolwork, chores or duties
• Has difficulty organizing tasks and activities
• Avoids/dislikes tasks that require sustained
  mental effort
• Often loses things necessary for tasks/activities
• Is easily distracted by extraneous stimuli
• Is often forgetful in daily activities

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Hyperactive/Impulsive Symptoms

• Fidgets with hands or feet or squirms in seat
• Often leaves seat in classroom or other
  situations where remaining seated is expected
• Runs or climbs excessively in inappropriate
  situations
• (In adults or adolescents, experiences inner
  restlessness)
• Has difficulty playing or engaging in leisure
  activities quietly
• Always on the go or acts like driven by a
  motor
• Talks excessively
• Often blurts out answers before questions have
  been completed
• Has difficulty awaiting turn
• Often interrupts/intrudes upon others

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Diagnostic Criteria

• Some symptoms causing impairment before age 7
• Impairment from symptoms in at least 2 settings
  (e.g. school/work and home)
• Clear evidence of clinically significant
  impairment in social, academic or occupational
  functioning
• Not due to another mental illness (e.g. PDD,
  Schizophrenia, Mood Disorder, Anxiety Disorder,
  Dissociative Disorder, Personality Disorder)

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Still (1902) described 43 children in his
practice who exhibited

• Aggressivity
• Defiance
• Resistance to discipline
• Excessive emotionality
• Inhibitory volition lacking
• Lawlessness
• Spitefulness
• Cruelty
• Dishonesty
• Problems with sustained attention
• Overactivity

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Stills Keynote characteristic

• Immediate gratification of the self
• Defined disorder as Defect of moral control

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31 malefemale ratio

• -Onset before age 7
• -Higher incidence of minor abnormalities
• -Accident proneness
• -Higher rates of alcoholism, criminality and
  affective disorders in biological relatives
• -Occasional microkinesia (Tic disorders)

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Proposed etiology (Still-1902)

• -Biologic predisposition
• -Probably hereditary
• -Possible association with pre/post-natal injury

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Current formulation of Stills patient
descriptions

• Comorbid
• ADHD
• Conduct Disorder (CD)
• Oppositional Defiant Disorder (ADHD)

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Postencephalitic Behavior Disorder

• 1917-1918 encephalitis epidemic child survivors
  exhibited
• Attentional impairments
• Dysregulation of activity
• Impulsivity
• Socially disruptive
• Cognitive problems (memory/concentration)
• Oppositional/defiant behavior conduct problems

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Brain Damage Syndrome

• Birth trauma (Shirley-1939)
• Lead toxicity (Byers Lord-1943)
• CNS infections , e.g. measles (Meyer
  Byers-1952)

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• MBD- Minimal Brain Damage Minimal Brain
  Dysfunction 1950s-60s
• Hyperactivity Hyperactive Child Syndrome,
  Less focus on Brain Damage 1960s
• Attention Deficits DSM III Attention Deficit
  Disorder (with/without Hyperactivity)1970s
• Attention Deficit Hyperactivity Disorder DSM
  III-R 1987

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The ADHD Brain

• Diffuse systems Brainstem, midbrain, cortex
• Decreased cortical size
• Deccreased corpus callosum size
• Decreased blood flow to striatum
• Abnormalities in fronto-striatal tracts
• Frontal-Prefrontal cortex dysfunction (Frontal
  Projection of deeper deficits)
• Working memory (RAM)
• Internalization of speech (Self-talk)
• Self-regulation of affect, motivation, anger
• Behavior analysis and synthesis
• Motor control, fluency, syntax

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Neuroimaging in the ADHD Brain

• SPECT/PET/fMRI
• Decreased blood flow
• Striatum
• Prefrontal cortex
• Dorsal and anterior cingulate cortex
• CT
• Decreased cortical size
• Asymmetry

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Neurochemical Dysregulation

• Norepinephrine
• Prefrontal cortex
• Locus ceruleus
• Dopamine
• Mesocortex
• Striatum
• Mesolimbic
• Cortical

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ADHD Assessment Child Adult

• Genetic History
• Medical History
• Psychiatric History
• Early School History
• Current Function in all spheres

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Genetic History

• 70 genetic etiology
• DRD4G Gene emerged _at_ 40,000 years ago
• ? evolutionary role (Hunter gene vs. Farmer
  gene)

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Medical History

• Prenatal trauma (viral infection/maternal
  stress/substance use/alcohol use/tobacco
  use/toxemia/eclampsia)
• Low birth weight
• Birth trauma (fetal distress/ hypoxia/anoxia/
  forceps delivery)
• Neurologic disorders (seizures/frontal lobe
  injury)
• Lead toxicity
• Sleep Apnea
• ? Thyroid Disease
• Medication side effects (Phenobarbital,dilantin,th
  eophylline)

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Substance use history

• Cocaine
• Ecstasy
• Stimulants
• Caffeine

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Psychosocial factors

• Cannot be considered causal factors but may
  exacerbate the disorder

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Psychiatric History

• Anxiety Disorders
• Depression
• Bipolar Disorder
• Personality Disorder

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Early School History

• Symptom onset before age 7
• Review report cards
• Obtain history from family
• With adults, explore recollected history of
  disciplinary referrals in school, grades, other
  symptoms that they recall

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Rating Scales (Initial and for ongoing
monitoring)

• Connors Parent Teacher Rating Scales
• Acters
• Child Attention Profile
• BASC/Achenbach CBCL/TRF/YSR
• ASRS (Adult Self Rating Scale)
• LOOK AT INDIVIDUAL RESPONSES. These are tools
  which help gather history about the diagnostic
  criteria, nothing more.

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Adult Diagnostic Approaches

• In addition to symptom checklists, explore
• History of multiple/frequent job changes/poor job
  performance
• Substance abuse patterns
• Relationship difficulties
• Traffic violations/accidents
• Comorbid anxiety depression

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Treatment Options

• Behavioral Interventions
• Medical Interventions
• Combined Interventions

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Behavioral Interventions

• Accomodations and Modifications in the classroom
• Parent Behavior Management Training
• ADHD Coaching
• Counseling Teach adaptive strategies

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Accomodations and Modifications

• Keep child in mainstream classroom
• Mandated by Section 504 of Rehabilitation Act of
  1973 (504 Plan)
• Mandated by Individuals with Disabilities
  Education Act of 1991(IDEA) under category of
  Other Health Impaired (OHI)
• Preferential Seating
• Positive cues
• Briefer lesson duration
• Decreased homework expectations
• Use homework organizer
• Coordinate school home via daily/weekly reports
• Prolonged time for test taking
• Opportunities for motor discharge (chores, etc.)

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Behavioral Programs

• Positive reinforcement using token programs/
  tangible rewards, modified to provide frequent
  powerful reinforcement
• Negative consequences using reprimands,
  response-cost systems (can be part of token
  system)
• Time out

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Medication Interventions

• First Line Treatments (AACAP Guidelines)
• Stimulants
• Methylphenidate (Ritalin, Concerta, Metadate,
  Focalin)
• Amphetamine (Dexedrine, Dextrostat, Adderall)
• Nonstimulants
• Atomoxetine(Strattera)

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Second Line Treatments

• Antidepressants (Buproprion/Wellbutrin,
  Venlafaxine/Effexor, Desipramine/Norpramine)
• Alpha Adrenergic Agonists (Clonidine/Catapres,
  Guanfacine/Tenex)
• Antinarcoleptics (Modafinil/Provigil)

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Stimulants

• Benzedrine (1931) First used in ADHD by Charles
  Bradley at Bradley Hospital 1937
• Methylphenidate (1944)
• Dextroamphetamine (1950)
• Until recently the only first line medications
  for ADHD

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Mechanism of Action

• Inhibit reuptake of Dopamine (DA) ,
  Norepinephrine (NE) in synapse
• Stimulate release of DA NA into synapse
  (amphetamine)
• Immediate onset of action

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Side Effect Profile

• Appetite suppression/weight loss
• Insomnia
• Withdrawal mood lability/irritability/rebound
• High abuse potential- Schedule C-II
• Tics
• Anxiety
• Increased Pulse/BP
• Blunting of personality (Zombie effect)

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Stimulant Delivery Systems

• Immediate Release
• Amphetamine Adderall(mixed amphetamine salts),
  Dextrostat (dexedrine)
• Methylphenidate Ritalin(methylphenidate/MPH),
  Focalin (D-methylphenidate)
• Sustained Release
• Amphetamine Adderall XR(mixed amphetamine
  salts), Dexedrine
  spansule(dextroamphetamine)
• Methylphenidate Concerta, Metadate CD, Ritalin
  LA, Ritalin SR

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Stimulants Sustained Release Delivery Systems

• Amphetamine
• Dexedrine spansule (capsule)
• Adderall XR (cap with beads, can sprinkle)
• Methylphenidate
• Ritalin LA (cap with beads, can sprinkle)
• Ritalin SR (wax matrix tablet, erratic release)
• Concerta (OROS osmotic pump/sponge capsule)
• Metadate CD (Cap with beads, can sprinkle)

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Release patterns of Sustained Release Stimulants

• Amphetamine
• Adderall- 50 immediate release, 50 in 4 hours
• Duration of action _at_ 12 hours
• Dexedrine Spansule- ?proportion
• Duration of action _at_ 6-8 hours

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• Methylphenidate
• Ritalin LA 50 immediate release, 50 in 4
  hours
• Duration of action _at_ 8 hours
• Metadate CD -30 immediate release, 70 in 3
  hours
• Duration of action _at_ 8 hours
• Concerta 20 immediate release, 80 sustained
  release
• Duration of actions _at_ 12 hours

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Methylphenidate

• Ritalin LA 50 immediate release, 50 in 4
  hours
• Duration of action _at_ 8 hours
• Metadate CD-30 immediate release, 70 in 3 hours
• Duration of Action _at_8 hours
• Concerta 20 immediate release, 80 sustained
  release
• Duration of actions _at_ 12 hours

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Dosing Stimulants

• Methylphenidate potency _at_ 50 of amphetamine
  potency
• Start with low dose to establish tolerability
• Titrate until no further improvement seen or side
  effects noted
• Underdosing is common concern
• No association between optimal dosage and age,
  weight or blood levels

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Approved Dosage Ranges Stimulants

• Methylphenidate
• Concerta 18-54 mg/day (note _at_ 10 loss of
  available drug)
• Available in 18, 27, 36 54 mg caps
• Metadate CD 10-60 mg/day
• Available in 10 20 mg caps
• Ritalin LA 20-60 mg/day
• Available in 20, 30 40 mg caps
• Ritalin SR 20-60 mg/day
• Available in 20 mg tabs

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Approved Dosage Ranges Stimulants

• Amphetamine
• Adderall, Adderall XR 5-40 mg/day
• Adderall- Available in 5, 7.5, 10, 12.5, 15, 20
  30 mg tabs
• Adderall XR Available in 5, 10, 15, 20, 25 30
  mg caps
• Dexedrine 2.5-40 mg/day
• Dexedrine Spansule- Available in 5, 10 15 mg
  caps
• Dexedrine - Available in 5 mg tabs
• Dextrostat Available in 5 10 mg tabs

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Choosing a Stimulant

• Begin with long acting preparation
• Improved compliance
• Avoid school stigma
• Longer duration of effect
• Consider delivery system
• Are sprinkled preparations necessary?

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Nonstimulant Atomoxetine (Strattera)

• Mechanism of Action Selective Norepinephrine
  Reuptake Inhibitor
• Stimulates noradrenergic neurons, increases
  dopamine in prefrontal cortex
• Stimulates noradregergic neurons in posterior
  ADHD tracts
• Slow onset of action, up to 4-6 weeks for full
  effect
• No abuse potential, not controlled, can be
  sampled, called in, refilled
• 24 hour efficacy

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Side effect profile- Atomoxetine (Strattera)-
Children

• Nausea/Dyspepsia
• Somnolence
• Dizziness
• Mood changes
• Increased pulse/BP

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Side effect profile-Atomoxetine (Strattera)-
Adults

• Dry Mouth
• Nausea/Dyspepsia
• Insomnia
• Decreased libido/erectile dysfunction
• Urinary retention

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Dosing Atomoxetine (Strattera)

• Approved dosage range- up to 1.4mg/kg or
  100mg/day
• No effect under .9 mg/kg
• Begin _at_ .5 mg/kg titrate to target dose of
  1.2-1.4 mg/kg over 3-4 days

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Factors to Consider in Choosing a First Choice
Medication

• Acuteness of Symptoms
• Pervasiveness of symptoms throughout the day
• Comorbidities
• History of family response to individual
  medications
• Family comfort level with controlled medications
  vs newer medication
• Ability of patient to swallow pill/capsule

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Dealing with Side Effects

• Stimulants
• Appetite suppression Add cyproheptadine
  (Periactin) 2mg BID
• Anxiety- consider adding SSRI (e.g fluoxetine)
• (Stimulants can down regulate serotonin)
• Insomnia- Melatonin up to 6mg H
• Alpha adrenergic agonists (guanfacine(Tenex),
  clonidine (Catapres) at HS (note possible
  cardiac effects)
• Withdrawal/rebound
• Change stimulant
• Add Atomoxetine(Strattera)
• Add alpha adrenergic agonist
• Tics
• Change to nonstimulant
• Add alpha adrenergic agonist
• Add risperidone(Risperdal) or other atypical
  antipsychotic

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Dealing with side effects Atomoxetine
(Strattera

• Nausea
• give on full stomach, if poor breakfast eaters,
  give after dinner
• Somnolence
• Give after evening meal
• Split into BID dosing
• Insomnia
• Change from AM to PM dosing (or vice versa)
• Split into BID dosing
• Use melatonin

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Agitation

• Consider Bipolar diagnosis
• Stimulants and atomoxetine may possibly
  precipitate mania
• Discontinue med immediately
• Assess level of risk, refer for emergency
  assessment if indicated
• Use benzodiazepines (e.g Lorazepam (Ativan),
  Clonazepam (Klonopin), observe for quick
  resolution of symptoms

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Second Line Medications

• Buproprion(Wellbutrin, Wellbutrin SR, Wellbutrin
  XL) Has some DA and NE activity
• Indicated for treatment of depression, smoking
  cessation
• Side Effects Insomnia
• Seizures
• Tics
• Recent concern possible precipitation of SI in
  children early in treatment for depression

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Dosing

• Begin at 50mg BID (Wellbutrin SR) or 100 mg QD
  (WellbutrinXL)
• Titrate to max 450mg(Wellbutrrin XL), 400 mg
  Wellbutrin/Wellbutrin SR
• 4 weeks to complete effect

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Modafinil(Provigil)-

• Indicated for treatment of narcolepsy. Unclear
  mechanism of action, does not bind to DA or NE
  receptors, but has stimulant-like properties,
  Schedule C-IV
• Dosing Effective dosing _at_ 200-400mg, available
  in 100 200 mg tabs
• Side effects
• Insomnia
• Headache
• Nausea
• ?addictive potential equivalent to MPH
• ? potential to precipitate mania

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Desipramine(Norpramin)-

• Tricyclic antidepressant with strong NE reuptake
  inhibition, previously widely used as second line
  ADHD med. _at_ 4 week onset of action.
• Dosing Adult-100-300mg/day
• Children- 25-100 mg/day (Blood levels
  available)

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Side effects

• Lethal in OD
• Cardiac arrythmias(several reports of sudden
  death in children-obtain EKG prior to starting
  and after initial dose and dosage increases)
• Sedation
• Blurred vision
• Dry mouth
• Constipation
• Dizziness

58
Alpha Adrenergic agonists

• Guanfacine(Tenex), Clonidine(Catapres)- Indicated
  for treatment of hypertension, also ameliorate
  tics, often used to calm impulsivity/hyperarousal
  in PTSD)
• Dosing Guanfacine Up to 1 mg QID
• Clonidine Up to 0.1 mg QID

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Side effects

• Sedation
• Headache
• Nausea
• Dizziness
• Hypotension
• NB _at_ 5 reported cases of sudden death in
  children when combined with MPH
• Obtain EKG prior to initiating and after
  initiating or changing dose.

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Why Medicate ADHD?

• Significant Morbidity and Mortality Associated
  with Untreated ADHD
• Increased incidence of substance abuse,
  depression and anxiety
• Increased risk of involvement in criminal justice
  system
• Increased incidence of automobile accidents,
  traffic violations
• Earlier first sexual activity, higher rate of
  teen pregnancy
• Lower levels of educational attainment
• Lower levels of job performance, more likely to
  be fired
• Higher divorce rate

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• Questions?