ADHD

Dr P.Kasi Krishna raja DPM DNB Asst proff Of Psychiatry

 Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder among school-age children Children with ADHD display the early onset of symptoms consisting of developmentally inappropriate overactivity, inattention, academic underachievement, and impulsive behavior. increased risk of ADHD children for delinquency, accidents, and substance abuse.

 ADHD is a familial disorder associated with differences in central nervous system structure, metabolism, and processing.

History of ADHD
Early 1900s inhibitory volition and defective moral control

1917-1918
encephalitis epidemic brain-injured child syndrome

1940s and 1950s

minimal brain damage and minimal brain dysfunction hyperkinetic impulse disorder

1970 on
attention and impulse control, in addition to hyperactivity problems in self-regulation and behavioral inhibition

Different Names for ADHD Through the years:

1902 Defects in moral character 1934 Organically driven 1940 Minimal Brain Syndrome 1957 Hyperkinetic Impulse Disorder 1960 Minimal Brain Dysfunction (MBD) 1968 Hyperkinetic Reaction of Childhood (DSM II) 1980 Attention Deficit Disorder - ADD (DSM III) withhyperactivity without-hyperactivity residual type
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ADHD Exposed
ADHD is identifiable via behavioral, not physical characteristics, making it more likely to be misunderstood. Misperceptions:
Behaviors that directly result from ADHD are not primarily attributable to poor parenting, lack of discipline, low motivation, or intentional trouble making. Not everything that fidgets and/or behaves defiantly is ADHD.

What Is ADHD?
Neurobehavioral disorder marked by:
Inattention Difficulties controlling impulses Excessive motor activity (hyperactivity)

Indicators of ADHD as a Developmental Disorder (Barkley, 1995)

Seen in early child development Behaviors clearly distinguish child from non-ADHD children Occurs across several situations (though not necessarily in all of them) Behaviors persistent over time Child not able to perform at age-appropriate levels Not accounted for by environment of social causes Related to brain function Associated with other biological factors that can affect brain function (i.e. head injuries, genetics)

ADHD Characteristics

Inattention Impulsivity Overactivity

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Inattention-Distractibility
Doesnt seem to listen Fails to finish assigned tasks Often loses things Cant concentrate Easily distracted Daydreams Requires frequent redirection Can be very quiet & missed
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Impulsivity-Behavioral Disinhibition
Rushing into things Careless errors Risk taking Taking dares Accidents/injuries prone Impatience Interruptions
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Restlessness Cant sit still Talks excessively Fidgeting Always on the go Easy arousal Lots of body movement

Hyperactivity - Overarousal

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Things We Can See (aka, Common Complaints)

Difficulties sustaining attention
Daydreaming Child doesnt listen Always losing things Forgetful Easily distracted Needs constant supervision Child doesnt finish anything he/she starts

Common Complaints (contd)

Problems with impulse control
Impatient/Difficulties waiting for things Always interrupting others Blurts out answers Doesnt take turns Tries to take shortcuts on many tasks (including chores, homework, etc.)

Common Complaints (contd)

Hyperactivity
Always on the go Squirmycant sit still Talks too much Frequently hums or makes odd noises Unable to put the brakes on motor activity Child has two speeds; asleep and awake

Mood Component
There is often a mood component with ADHD:
Moodiness (difficulty regulating mood) Bursts of Hot temper (difficulty controlling temper)

It is possible to have ADHD and Depression, ADHD and Anxiety, ADHD and Bipolar, ADHD and Anger, or any combination of these. Irritability, anger, rebelliousness, temper tantrums, grumpiness, defiance or aggressive behavior can all be symptoms of a treatable Mood Disorder.

What Do These Behaviors Have in Common?

Problem isnt as much sustaining attention as it is sustaining inhibitionthis is the hallmark of ADHD Inhibition: a mental process that restrains an action (behavior) or emotion Problems of inhibition are not a matter of choice, but are instead a result of what is (or is not) going on in the childs brain

DSM-IV Criteria
Developmentally Inappropriate Levels of Either Inattention and/or Hyperactive/Impulsive Behavior Duration of 6 Months Cross-setting Occurrence of Symptoms Impairment in Major Life Activities Onset of Symptoms/Impairment by 7 Symptoms Not Better Explained by Other Disorders: e.g., Severe MR, PDD, Psychosis, Bipolar, etc. Three Subtypes Inattentive, Hyperactive, or Combined Types Affects 5-8% of children, 4-5% of adults Disorder is found universally

Comorbid DSM-IV Disorders

Oppositional Defiant Disorder (40-70%)
ADHD contributes to and likely causes ODD

Conduct Disorder (20-56%) Delinquent/Antisocial Activities (18-30%)

Psychopathy rates unknown but 20% of CD

Anxiety Disorders (10-40%; referral bias!)

Related to poor emotion regulation than to fear

Major Depression (0-45%; 27% by age 20)

Likely genetic linkage to ADHD

Bipolar Disorder (0-27%; likely 6-10% max.)

Not documented in any follow-up studies to date

Childhood Developmental Risks

Language Disorders (10-60%) Developmental Coordination Disorder (50+%) Accident Proneness 1.5 to 4x risk Poor School Performance (90%+) Low Academic Achievement (10-15 pt. deficit) Low Average Intelligence (7-10 point deficit) Learning Disabilities (24-70%) Increased Parent-Child Conflict & Stress Peer Relationship Problems (50-70%+) Poor Emotional Self-control Greater Antisocial Activities in Adolescence
Related primarily to development of early CD

ADHD and the Human Brain

Portions of brains frontal lobe are responsible for Executive functions:
Consolidating information from other areas of the brain Considers potential consequences and implications of behaviors Puts brakes on (inhibits) impulsive reactions Initiates appropriate response to environment

ADHD and the Brain (contd)

Research suggests that in in children with ADHD, these executive areas of the brain are under-active Increasing the activity level in these areas of the ADHD brain have been shown to decrease behavioral symptoms. This is the logic behind using Stimulant medications as a first line treatment for the disorder.

Other Neurobiological Conditions Related to ADHD:

Central Auditory Processing Disorder (CAPD) Sensory Integration Disorder Motor Planning Disorder Self-Regulatory Disorder Autistic Spectrum Disorder - PDD, MSD, Globally Delayed, Autistic Neurological Conditions: Epilepsy, Tourette Syndrome
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What Research is Telling Us about ADHD

Genetically transmitted in 70-95% of cases Results from chemical imbalance or deficiency in certain neurotransmitters-chemicals which help brain regulate behavior Rate at which brain uses glucose, its main energy source, is lower in subjects with ADHD than those without (Zametkin et al, 1990) Depressed release of Dopamine might have role in ADHD (Volkow et al, 2003)
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Research also tells us about ADHD that:

Central pathological deficits of ADHD are linked to several specific brain regions Frontal Lobe Its connections to Basal Ganglia Their relationships to central aspect of Cerebellum Less electrical activity in brain & show less reactivity to stimulation in one or more of above brain regions Brains are 3-4% smaller-in more severe-frontal lobes, temporal gray matter, caudate nucleus & cerebellum were smaller
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PET Scan of Metabolism of Glucose Adult Brain with ADHD

Positron Emission Tomography (PET) Pictures of Adult with ADHD Normal Adult

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ADHD & LD lead to Diminished Executive Functions

Deficient self-regulation of behavior, mood, response Impaired ability to organize/plan behavior over time Inability to direct behavior toward future Diminished social effectiveness & adaptability

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What is the Impact of these Disorders?

Neurologically based behavioral issues can keep child from developing normally Lack of full coordination of gross & fine motor skills Lack of complete age appropriate speech, language & communications Impaired self-esteem
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What is the Impact of ADHD on people? (Barkley, 2002)

32-40% of students with ADHD drop out of school Only 5-10% will complete college 50-70% have few or no friends 70-80% will under-perform at work 40-50% will engage in antisocial activities More likely to experience teen pregnancy & sexually transmitted diseases Have more accidents & speed excessively Experience depression & personality disorders
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Assessment Tools
Conners Rating Scales, by parents and teachers, most common (subjective) WISC III (Wechsler Intelligence Scale for Children, Also shows Depression) TOVA (Test of Variables of Attention) Wisconsin Card sorting (tests Frontal Lobe)~

TOVA
The T.O.V.A. was developed by Dr Greeenberg, an authority on hyperactivity and ADHD, and a leader in the field for the past 25 years. The T.O.V.A is a 22.5 minute computerized assessment (visual or auditory) which in conjunction with teacher and parent behavior rating scales, is a highly effective screening tool for ADHD.~

Overview: Medication Treatments for ADHD

FDA-Approved Treatments
Stimulants
Schedule II Drugs Potentiate dopamine/norepinephrine neurotransmission

Atomoxetine (Strattera; Eli Lilly)

Non-stimulant Norepinephrine reuptake inhibitor

Off-Label Treatments
Modafanil (Provigil; Cephalon) arousal-promoting Guanfacine - alpha-2 agonist Clonidine - alpha-2 agonist Bupropion (Wellbutrin family) norepinephrine/dopamine reuptake inhibitor Tricyclic Antidepressants

The Stimulant Landscape: Drugs & Companies

Amphetamine Line Methylphenidate Line
Extended Release Formulations (up to 12 hours) once daily
Concerta tablets (McNeil Pediatrics) methylphenidate Focalin XR capsules (Novartis) dexmethylphenidate Daytrana Transdermal Patch (Shire) methylphenidate

Extended Release Formulations (up to 12 hours) once daily

Vyvanse capsules (Shire) lisdexamfetamine, d-amphetamine/L-lysine prodrug; approved 2/07, launched 2nd quarter 2007 Adderall XR capsules (Shire) mixed amphetamine salts of dextroamphetamine & racemic d/l-amphetamine Dexedrine SR spansules (GlaxoSmithKline) & generic versions of Dexedrine SR dextroamphetamine

Intermediate-Release Formulations, Second-Generation (6-8 hours) 1-2x daily

Ritalin LA capsules (Novartis; Celgene); ANDA filed for generics 11/2007 with Paragraph IV certification Metadate CD Capsules (UCB) methylphenidate +metadate ER

Immediate Release Formulations (3-6 hours) 2-3 times daily

Adderall tablets (Barr/Duramed-Shire Deal) Generic versions of Adderall (ie, mixed amphetamine salts) Dexedrine tablets (GlaxoSmithKline) dextroamphetamine Generic versions of Dexedrine

Intermediate-Release Formulations, FirstGeneration (3-6 hours) 1-2x daily

Ritalin SR tablets (Novartis) & generic versions - methylphenidate Metadate ER tablets & generic versions methylphenidate

Immediate Release Formulations (2-4 hours), 2-4x daily

Ritalin tablets (Novartis) & generic versions methylphenidate Focalin tablets (Novartis) & generic versions (approved 2/07) - dexmethylphenidate

The Prodrug Concept

Lisdexamfetamine dimesylate is a therapeutically inactive prodrug The active ingredient d-amphetamine is covalently linked to the amino acid l-lyine The active ingredient d-amphetamine is released during the enzymatic breakdown of the prodrug in the gut and liver Saturation kinetics govern the breakdown into the active d-amphetamine form (unlike other stimulants) Pharmacokinetic properties associated with the prodrug mechanism of action confer unique clinical and safety properties First-in-class prodrug stimulant