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Attention Deficit
Hyperactivity Disorder




                    Dr. Santanu Ghosh, MD
                    Assistant Professor, Psychiatry
                    Tripura Medical College, Agartala
The Difficult Child…..
A mother brings her 8-year old son for evaluation after he is
suspended from the school for jumping on his seat, teasing
other children, and not following directions. He spends two to
three hours a night with homework that he never successfully
completes. His mother wants to know what is wrong with her
child.

The child is a victim of…………
Attention Deficit
Hyperactivity Disorder
ADHD ?

         •   A condition affecting children and adults
         •   Characterized by problems with:




Attention,               Impulsivity             Overactivity
ADHD Prevalence


       Physician office visits in 2001          9.7 L


Mental health referral for children             30-50%


       Sex Ratio                           Male> Female
                                               3-4:1

       Children                              Prevalence : 7.5%

                                         • 40- 70% of adolescence
       Persists in                       • Up to 50% of adults
Subtypes of ADHD

Predominately          Predominately                Combined type
  Inattentive          Hyperactive-Impulsive




                Attention Deficit Hyperactivity Disorder
ClinicalADHD: Etiology
                    Presentation



    Inattentiveness
Difficulty sustaining         Hyperactivity                  Impulsivity
 attention
                               Often fidgets
Makes careless mistakes in
                              Runs about/climbs          Blurt s out answers
 school work
                              Difficulty in obeying      Difficulty awaiting turn
Fails to complete task
                              Often on the go            Often interrupt others
Disinterest which requires
                              Talks excessively
 mental effort

Forgetful, Often loses
 things
                                 •   Impairment
                                 •   Duration >6 months
ADHD Impact
                  ADHD Impact
                                                 Ch
                               Academic             ild   ren
                              limitations

             Occupational/                  Relationships
              vocational
Adults




                                                    Low self
            Legal
         difficulties        ADHD                   esteem



            Motor vehicle
             accidents                       Injuries
                          Smoking and
                        substance abuse

                             Adolescents
ADHD: Etiology
    Etiology

                Neuroanatomical
                 Neurochemical



Environmental
   (family)                       Genetic
                ADHD              origins



                    CNS
                   insults
ADHD and the Brain




                                                     PET scan shows
Decreased blood flow to                             decreased glucose
 prefrontal cortex and                            metabolism throughout
                          Diminished arousal of
pathways connecting to                                    brain
                           the Nervous System
limbic system (caudate
 nucleus and striatum)
ADHD and the Brain
            ADHD and the Brain cont..


MRIs of ADHD patients show:

                              Abnormal development in the frontal and striatal
       Smaller anterior       regions
      right frontal lobe


                              Decreased communication and processing of
          Significantly
                              information between hemispheres
         smaller corpus
         callosum

                              Immature basal ganglia
            Smaller
            caudate
            nucleus
Genetics

                                        Dopamine genes
 Parents with ADHD have > 50%

 chance of having a child with ADHD     •DA type 2 gene

                                        •DA transporter gene (DAT1)



About 25% of children with
ADHD have parents who meet the          Dopamine receptor (DRD4,
formal diagnostic criteria for          “repeater gene”) is over-
ADHD                                    represented in ADHD patients
Genetics contd..



                  Learning of behavior


                          Motivation
                           Emotion


                       Working memory

         Affects executive function & attention



 DRD4 affect the post synaptic sensivity in the
 prefrontal &frontal cortex.
Catecholaminergic Neurotransmission
   Catecholaminergic Neurotransmission
                 Relative to ADHD
                        Relative to ADHD
      Dopamine                               Norepinephrine

• Striatal-prefrontal                •   Prefrontal
• Enhances signal                    •   Dampens noises
• Improves attention                      - Distractibility
  - Focus                                 - Shifting
  - Vigilance                        •   Executive operations
  - Acquisition                      •   Increases inhibition
  - On task behavior                      - Behavioral
  - On task cognitive                     - Cognitive
  - perception                            - Motoric


                 Solanto.Stimulant Drugs & ADHD. Oxford; 2001
Dopamine in the Brain
Other Causes
                                            Brain insults such as injury to frontal
                                            Environmental factors like Brain
                                            insults such as injury to frontal
                                            region, premature birth,
                                   Injury   complications during pregnancy, low
                                            social class




                              Pb            Zn

Sub clinical lead exposure:                    Serum Zinc- low levels in hyper
inattention, antisocial                        actives
behavior, Hyperactivity
(Bellinger 2004)
Assessment & Diagnosis


 A good clinical history

A thorough developmental history

   Toddlers may be unable to be seated

   Pre school & school children may be hyperactive, naughty

   Older children are more inattentive.
TOOLS - THE STROOP TEST to asses attention

Black Words
Black Words
The Coloured words
ADHD - Rating Scale
                      Prognosis of ADHD


                                                        Conner’s
     Home                       School                  Teachers
    Version                     Version                 Rating
                                                        Scale




                       •   Contains a set of
• Contains a set of                              •   Aged 3-17 years
                           18 questions
  18 questions
                       •   Addressing            •   Contains 28 or 39
• Addressing               attention                 questions
                           learning abilities,
  attention and                                  •   Addresses
                           organizing
  behavior                                            Conduct problem,
                           abilities,
                                                      hyperactivity,
                           behavior and               inattentive-passive,
                           memory                     and hyperactivity
Differential Diagnosis


Anxiety                              Conduct
disorder                Opposition   Disorder
           Depression   Defiant
                        Disorder
Comorbidities:



                               ADHD


          49%
                  11%
                 7%
                               Depression
           11%



                 Conduct Disorder
Anxiety
Prognosis of ADHD



                                                                                     With a
                                                                                     combination of
                                                                                     medication and
                                                        If not properly              psychosocial and
                                                        treated individuals          behavioral
                                                        across age-span are          interventions most
                                                        at risk                      children’s
                           With increasing age                                       symptoms are
                           •Hyperactivity decreases                                  ameliorated
                           •Inattention, impulsivity,
80% of affected children   disorganization &
symptoms of ADHD           relationship difficulties
persist into adolescence   persist
and adulthood
                                                               Nelson’s Textbook of Pediatrics, 17th Ed p 109-110
Understanding Adult ADHD

Do you have difficulty concentrating or focusing      your attention on
one thing?

Do you often start multiple projects at the same time, but rarely finish
them?

Do you have trouble with organization?

 Do you procrastinate on projects that take a lot of attention to detail?
Understanding Adult ADHD contd..


 Do you have problems remembering appointments or obligations?
 Do you have trouble staying seated during meetings or other
  activities?

 Are you restless or fidgety?

 Do you often lose or misplace things?
Treatment Goals

• A child-specific, individualized treatment program should be
  developed for children

• A goal of maximizing function to
   – improve relationships and performance at school,
   – decrease disruptive behaviors,
   – promote safety,
   – increase independence and
   – improve self esteem.
Treatment Options




Medication   Behavioral Therapy   Psychotherapy   Educational
                                                  Techniques
Treatment Options
• Medications are the first line of choice for ADHD management

   – Help treating the core symptoms of ADHD



• Psychotherapy and behavioral therapies

   – Effective in management of co morbid disorders with ADHD
Childhood ADHD: Treatment

              The Triangle principle

                    Pharmacotherapy




                            Parents
  School
                           Education
Instruction
                            and BT
Medications
• Stimulants
  – Methylphenidate & derivatives
  – Amphetamine & derivatives
• Non – Stimulants
  – Antidepressants
  – Antipsychotics
  – Atomoxetine
How do Stimulants Act?
• Non specific in action
• Increase levels of dopamine and
  norepinephrine
• Increase dopamine levels in
  – PFC
  – Striatum
  – Nucleus accumbens
Stimulants – The Problem

•Abuse Potential
•Tics
•Anorexia
•Insomnia
Stimulants - Methylphenydate
     Methyl Phenydate


Blocks NT transporter


Decrease DA & NE uptake

Increased DA in striatum &
PFC

Improves hyperactivity &
attention
Atomoxetine
• Initially developed as an antidepressant however found
  more effective in ADHD



• Initially called as Tamoxetine but name changed to
  atomoxetine to avoid confusion with tamoxifen (for
  advanced breast cancer)
Mode of Action of Atomoxetine

• Selective NE reuptake inhibitor

• Inhibits NE/DA re uptake in PFC (NET>DAT)

   – DA taken up by NET in PFC

• Increase in extra-cellular NE (not DA) in subcortex (nucleus
  accumbens/striatum)
• But no increase in DA in sub-cortex & hence no tics/abuse
Mode of Action (cont’d…)

• A highly selective and a potent inhibitor of presynaptic NE
  transporter
• Increases extracellular concentrations of DA 3 fold in
  prefrontal cortex
• Does not alter DA concentrations in striatum and nucleus
  accumbens
   – No motoric or abuse potential
• Increases levels of catecholamines in PFC



          Bymaster FP, et al, Neuropsychopharmacology, 2002, 27(5), 699 - 711
Action on Dopamine

• In PFC Dopamine moves with the aid of NE transporter

• Lack of dopamine transporters in PFC

• Atomoxetine blocks NE transporter and increases DA in

  synaptic cleft
Atomoxetine




   Release acetylcholine
   Release acetylcholine


Improves attention ,cognition
 Improves attention ,cognition

Dosage-0.5mg/kg-1.2mg/kg
Dosage-0.5mg/kg-1.2mg/kg
                                 No abuse potential
PRE-FRONTAL CORTEX




        /DA                              /DA
                   Atemoxetine




Post-                            Post-
Indications
• FDA approved in November 2002 for treatment of ADHD

• The first non stimulant drug for ADHD after debut of
  methylphenidate for about 40 years
Recent Warnings

• Atomoxetine increased the risk of suicidal ideation in short-term

  studies in children or adolescents with Attention Deficit/Hyperactivity

  Disorder (ADHD).

• Patients started on therapy should be monitored closely for suicidal

  thinking and behavior.
Precautions
• Suicidal thought
• Severe liver injury
   – To be discontinued in patients with jaundice or
     laboratory evidence of liver injury, and should not be
     restarted
Other agents

• TCAs (desipramine or imipramine) cardiotoxicity

• Bupropion – anti depressant activating than sedating, insomnia,

  lower seizure threshold & tics
NON PHARMACOLOGICAL TREATMENT

Parent behavior management training
•Parenting skills training to implement BT programme at home
•Contingency programme
•Positive reinforcement
•Time out
•To ignore negative behavior



Social skills training
•Aim is to develop social relationship
•Waiting for turn, sharing toys ,asking for help.
Non pharmacological treatment

CBT - Cognitive Behavior Therapy

 helpful in adolescents, they recognizes social cues,
 determines action in situations
Other behavioral

 Daily activity scheduling

Training teachers / school
ADHD

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ADHD

  • 1. Attention Deficit Hyperactivity Disorder Dr. Santanu Ghosh, MD Assistant Professor, Psychiatry Tripura Medical College, Agartala
  • 3.
  • 4. A mother brings her 8-year old son for evaluation after he is suspended from the school for jumping on his seat, teasing other children, and not following directions. He spends two to three hours a night with homework that he never successfully completes. His mother wants to know what is wrong with her child. The child is a victim of…………
  • 6. ADHD ? • A condition affecting children and adults • Characterized by problems with: Attention, Impulsivity Overactivity
  • 7. ADHD Prevalence Physician office visits in 2001 9.7 L Mental health referral for children 30-50% Sex Ratio Male> Female 3-4:1 Children Prevalence : 7.5% • 40- 70% of adolescence Persists in • Up to 50% of adults
  • 8. Subtypes of ADHD Predominately Predominately Combined type Inattentive Hyperactive-Impulsive Attention Deficit Hyperactivity Disorder
  • 9. ClinicalADHD: Etiology Presentation Inattentiveness Difficulty sustaining Hyperactivity Impulsivity attention  Often fidgets Makes careless mistakes in Runs about/climbs Blurt s out answers school work Difficulty in obeying Difficulty awaiting turn Fails to complete task Often on the go Often interrupt others Disinterest which requires Talks excessively mental effort Forgetful, Often loses things • Impairment • Duration >6 months
  • 10.
  • 11. ADHD Impact ADHD Impact Ch Academic ild ren limitations Occupational/ Relationships vocational Adults Low self Legal difficulties ADHD esteem Motor vehicle accidents Injuries Smoking and substance abuse Adolescents
  • 12. ADHD: Etiology Etiology Neuroanatomical Neurochemical Environmental (family) Genetic ADHD origins CNS insults
  • 13. ADHD and the Brain PET scan shows Decreased blood flow to decreased glucose prefrontal cortex and metabolism throughout Diminished arousal of pathways connecting to brain the Nervous System limbic system (caudate nucleus and striatum)
  • 14. ADHD and the Brain ADHD and the Brain cont.. MRIs of ADHD patients show: Abnormal development in the frontal and striatal Smaller anterior regions right frontal lobe Decreased communication and processing of Significantly information between hemispheres smaller corpus callosum Immature basal ganglia Smaller caudate nucleus
  • 15. Genetics Dopamine genes Parents with ADHD have > 50% chance of having a child with ADHD •DA type 2 gene •DA transporter gene (DAT1) About 25% of children with ADHD have parents who meet the Dopamine receptor (DRD4, formal diagnostic criteria for “repeater gene”) is over- ADHD represented in ADHD patients
  • 16. Genetics contd.. Learning of behavior Motivation Emotion Working memory Affects executive function & attention DRD4 affect the post synaptic sensivity in the prefrontal &frontal cortex.
  • 17. Catecholaminergic Neurotransmission Catecholaminergic Neurotransmission Relative to ADHD Relative to ADHD Dopamine Norepinephrine • Striatal-prefrontal • Prefrontal • Enhances signal • Dampens noises • Improves attention - Distractibility - Focus - Shifting - Vigilance • Executive operations - Acquisition • Increases inhibition - On task behavior - Behavioral - On task cognitive - Cognitive - perception - Motoric Solanto.Stimulant Drugs & ADHD. Oxford; 2001
  • 19.
  • 20. Other Causes Brain insults such as injury to frontal Environmental factors like Brain insults such as injury to frontal region, premature birth, Injury complications during pregnancy, low social class Pb Zn Sub clinical lead exposure: Serum Zinc- low levels in hyper inattention, antisocial actives behavior, Hyperactivity (Bellinger 2004)
  • 21. Assessment & Diagnosis  A good clinical history A thorough developmental history  Toddlers may be unable to be seated  Pre school & school children may be hyperactive, naughty  Older children are more inattentive.
  • 22. TOOLS - THE STROOP TEST to asses attention Black Words Black Words
  • 24. ADHD - Rating Scale Prognosis of ADHD Conner’s Home School Teachers Version Version Rating Scale • Contains a set of • Contains a set of • Aged 3-17 years 18 questions 18 questions • Addressing • Contains 28 or 39 • Addressing attention questions learning abilities, attention and • Addresses organizing behavior Conduct problem, abilities, hyperactivity, behavior and inattentive-passive, memory and hyperactivity
  • 25. Differential Diagnosis Anxiety Conduct disorder Opposition Disorder Depression Defiant Disorder
  • 26. Comorbidities: ADHD 49% 11% 7% Depression 11% Conduct Disorder Anxiety
  • 27. Prognosis of ADHD With a combination of medication and If not properly psychosocial and treated individuals behavioral across age-span are interventions most at risk children’s With increasing age symptoms are •Hyperactivity decreases ameliorated •Inattention, impulsivity, 80% of affected children disorganization & symptoms of ADHD relationship difficulties persist into adolescence persist and adulthood Nelson’s Textbook of Pediatrics, 17th Ed p 109-110
  • 28. Understanding Adult ADHD Do you have difficulty concentrating or focusing your attention on one thing? Do you often start multiple projects at the same time, but rarely finish them? Do you have trouble with organization?  Do you procrastinate on projects that take a lot of attention to detail?
  • 29. Understanding Adult ADHD contd..  Do you have problems remembering appointments or obligations?  Do you have trouble staying seated during meetings or other activities?  Are you restless or fidgety?  Do you often lose or misplace things?
  • 30. Treatment Goals • A child-specific, individualized treatment program should be developed for children • A goal of maximizing function to – improve relationships and performance at school, – decrease disruptive behaviors, – promote safety, – increase independence and – improve self esteem.
  • 31. Treatment Options Medication Behavioral Therapy Psychotherapy Educational Techniques
  • 32. Treatment Options • Medications are the first line of choice for ADHD management – Help treating the core symptoms of ADHD • Psychotherapy and behavioral therapies – Effective in management of co morbid disorders with ADHD
  • 33. Childhood ADHD: Treatment The Triangle principle Pharmacotherapy Parents School Education Instruction and BT
  • 34. Medications • Stimulants – Methylphenidate & derivatives – Amphetamine & derivatives • Non – Stimulants – Antidepressants – Antipsychotics – Atomoxetine
  • 35. How do Stimulants Act? • Non specific in action • Increase levels of dopamine and norepinephrine • Increase dopamine levels in – PFC – Striatum – Nucleus accumbens
  • 36. Stimulants – The Problem •Abuse Potential •Tics •Anorexia •Insomnia
  • 37. Stimulants - Methylphenydate Methyl Phenydate Blocks NT transporter Decrease DA & NE uptake Increased DA in striatum & PFC Improves hyperactivity & attention
  • 38. Atomoxetine • Initially developed as an antidepressant however found more effective in ADHD • Initially called as Tamoxetine but name changed to atomoxetine to avoid confusion with tamoxifen (for advanced breast cancer)
  • 39. Mode of Action of Atomoxetine • Selective NE reuptake inhibitor • Inhibits NE/DA re uptake in PFC (NET>DAT) – DA taken up by NET in PFC • Increase in extra-cellular NE (not DA) in subcortex (nucleus accumbens/striatum) • But no increase in DA in sub-cortex & hence no tics/abuse
  • 40. Mode of Action (cont’d…) • A highly selective and a potent inhibitor of presynaptic NE transporter • Increases extracellular concentrations of DA 3 fold in prefrontal cortex • Does not alter DA concentrations in striatum and nucleus accumbens – No motoric or abuse potential • Increases levels of catecholamines in PFC Bymaster FP, et al, Neuropsychopharmacology, 2002, 27(5), 699 - 711
  • 41. Action on Dopamine • In PFC Dopamine moves with the aid of NE transporter • Lack of dopamine transporters in PFC • Atomoxetine blocks NE transporter and increases DA in synaptic cleft
  • 42. Atomoxetine Release acetylcholine Release acetylcholine Improves attention ,cognition Improves attention ,cognition Dosage-0.5mg/kg-1.2mg/kg Dosage-0.5mg/kg-1.2mg/kg No abuse potential
  • 43. PRE-FRONTAL CORTEX /DA /DA Atemoxetine Post- Post-
  • 44. Indications • FDA approved in November 2002 for treatment of ADHD • The first non stimulant drug for ADHD after debut of methylphenidate for about 40 years
  • 45. Recent Warnings • Atomoxetine increased the risk of suicidal ideation in short-term studies in children or adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). • Patients started on therapy should be monitored closely for suicidal thinking and behavior.
  • 46. Precautions • Suicidal thought • Severe liver injury – To be discontinued in patients with jaundice or laboratory evidence of liver injury, and should not be restarted
  • 47. Other agents • TCAs (desipramine or imipramine) cardiotoxicity • Bupropion – anti depressant activating than sedating, insomnia, lower seizure threshold & tics
  • 48. NON PHARMACOLOGICAL TREATMENT Parent behavior management training •Parenting skills training to implement BT programme at home •Contingency programme •Positive reinforcement •Time out •To ignore negative behavior Social skills training •Aim is to develop social relationship •Waiting for turn, sharing toys ,asking for help.
  • 49. Non pharmacological treatment CBT - Cognitive Behavior Therapy  helpful in adolescents, they recognizes social cues, determines action in situations Other behavioral  Daily activity scheduling Training teachers / school

Editor's Notes

  1. ADHD is most likely caused by a complex interplay of factors Biologic factors that predispose an individual for ADHD include post-traumatic or infectious encephalopathy, lead poisoning, and fetal alcohol syndrome Environmental influences include abuse or neglect, family adversity, and situational stress Emerging literature provides support for the hypothesis that abnormalities in frontal networks or frontal-striatal dysfunction and catecholamine dysregulation are involved Family and twin studies reveal compelling data regarding the genetic origin of ADHD; and recent advances in neuroimaging techniques have promoted closer study of neuroanatomic correlates
  2. ADHD is most likely caused by a complex interplay of factors Biologic factors that predispose an individual for ADHD include post-traumatic or infectious encephalopathy, lead poisoning, and fetal alcohol syndrome Environmental influences include abuse or neglect, family adversity, and situational stress Emerging literature provides support for the hypothesis that abnormalities in frontal networks or frontal-striatal dysfunction and catecholamine dysregulation are involved Family and twin studies reveal compelling data regarding the genetic origin of ADHD; and recent advances in neuroimaging techniques have promoted closer study of neuroanatomic correlates