ADHD Bipolar Disorder

Attention-Deficit/Hyperactivity Disorder vs.
Bipolar Disease in the Pediatric Population

Richard G Petty MD, MSc, MRCP(UK),
MRCPsych,
Promedica Research Center,
Georgia State University College of Health
Sciences,
Loganville, Georgia,
USA
rpettyus@aol.com

Sunday, July 26, 2009

Disclosure
Richard G. Petty, MD, MSc, MRCP(UK), MRCPsych
 Consultant
 AstraZeneca; Bristol Myers Squibb; Eli Lilly and Company;
Janssen Pharmaceuticals
 Speaker’s Bureau
 Abbott Laboratories; AstraZeneca; Avanir Pharmaceuticals;
Janssen Pharmaceuticals
 Grant Support
 British Diabetic Association; Bristol Myers Squibb; British Heart
Foundation; Du Pont Merck, Inc.; Eli Lilly and Company; Janssen;
Medical Research Council (UK); National Institute of Mental
Health; Pfizer
 Dr. Petty’s presentation will include the discussion of off-
label, experimental, and/or investigational use of drugs or
devices

Attention-Deficit/Hyperactivity Disorder and
Bipolar Disorder

 There are four key questions:
 Are they two separate illnesses?
 Are they two overlapping syndromes?
 Are they sets of coexistent symptoms?
 How often is Attention-Deficit/Hyperactivity Disorder an
early symptom or warning sign of impending bipolar
disorder?

 Do these questions matter?


History of Attention-Deficit/Hyperactivity
Disorder (ADHD)
• Mid-1800s: Minimal Brain Damage
• 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) with-
hyperactivity without-hyperactivity residual type
• 1994-present: Attention-Deficit/Hyperactivity Disorder:
• 314.01: ADHD, Combined Type
314.00: ADHD, Predominantly Inattentive type
314.01: ADHD, Predominantly Hyperactive-Impulsive Type


ADHD Statistics

• 3-5% of all U.S. school-age children are
estimated to have this disorder
• 5-10% of the entire U.S. population
• Males are 3 to 6 times more likely to have
diagnosed ADHD than are females
• At least 50% of ADHD sufferers have another
diagnosable mental disorder


Diagnostic Features
 Persistent pattern of:
 Inattention
 Hyperactivity
 Impulsivity


Components of Attention

 Arousal and alertness
 External or receptive attention: sensory processing and
interpretation
 Internal or reflective attention
 Processing attention or selective attention
 Focus
 Filtering
 Inhibition of sensation
 External or expressive attention
 Working memory


Diagnosing ADHD: DSM-IV

 Inattentiveness:

Has a minimum of 6
symptoms regularly for the
past six months

Symptoms are present at
abnormal levels for stage of
development


• Lacks attention to detail;
makes careless mistakes
 Inattentiveness: • Has difficulty sustaining
attention
• Doesn’t seem to listen
Has a minimum of 6
• Fails to follow through/fails to
symptoms regularly for the finish projects
past six months
• Has difficulty organizing
tasks
Symptoms are present at • Avoids tasks requiring
abnormal levels for stage of mental effort
development • Often loses items necessary
for completing a task
• Easily distracted
• Is forgetful in daily activities



• Hyperactivity/
Impulsivity:

Has a minimum of 6
symptoms regularly for the
past six months.

Symptoms are present at
abnormal levels for stage of
development


• Fidgets or squirms
excessively
• Hyperactivity/ • Leaves seat when
Impulsivity: inappropriate
• Runs about/climbs
extensively when
Has a minimum of 6 inappropriate
symptoms regularly for the • Has difficulty playing quietly
past six months. • Often “on the go” or “driven
by a motor”
Symptoms are present at • Talks excessively
abnormal levels for stage of • Blurts out answers before
development question is finished
• Cannot await turn
• Interrupts or intrudes on
others



• Symptoms causing impairment
 Additional present before age 7
Criteria: • Impairment from symptoms
occurs in two or more settings
• Clear evidence of significant
impairment (social, academic,
etc.)
• Symptoms not better accounted
for by another mental disorder


Problems of Diagnosis

 Subjectivity of Criteria
 Inconsistent evaluations--presence of symptoms
usually given by teacher or parent
 Studies have shown that the number of
diagnosed cases of ADHD decreased 80% when
observations of parent, teacher and physician
were used rather than just one source
 Symptoms in females more subtle---leads to
under-diagnosis


ADHD and the Brain
 Diminished arousal of
some regions of the
nervous system
 Decreased blood flow to
prefrontal cortex and
pathways connecting to
limbic system (caudate
nucleus and striatum)
 PET scan shows
decreased glucose
metabolism throughout Comparison of normal brain (left) and
brain brain of ADHD patient.


ADHD and the Brain II
 Similarities of ADHD symptoms to those from
injuries and lesions of frontal lobe and prefrontal
cortex
 MRI scans of ADHD patients consistently show:
• Smaller anterior right frontal lobe
 abnormal development in the frontal and striatal regions
• Significantly smaller splenium of corpus callosum
 decreased communication and processing of information
between hemispheres
• Smaller caudate nucleus


What Causes ADHD?
 Underlying cause of these differences is still
unknown; there is much conflicting data between
studies
 Strong evidence of genetic component
 Predominant theory: catecholamine neurotransmitter
dysfunction or imbalance
 Decreased dopamine and/or norepinephrine uptake in brain
 Theory supported by positive response to stimulant
treatment
 Recent study in mice indicates possible lack of
serotonin as a factor
 Diet
 Constant over-stimulation


Inadequately Treated Attention
Deficit Hyperactivity Disorder May
Have Serious Consequences


Ch
Academic ildr
en
limitations

Occupational/ Relationships
vocational
Adults

Legal
difficulties ADHD Low self
esteem

Motor vehicle
accidents Injuries

Smoking and
substance abuse

Adolescents


ADHD: Impact of No Treatment or
Under-Treatment

Health Care
System
Family
3-5x increase in Parental
50% increased in bicycle accidents1 Patient Divorce
or Separation11,12
33% increase in ER visits2
2-4 x increase in Sibling Fights13
2-4 x more motor
vehicle accidents3-5

Society Employer
School & Occupation Increased Parental
Substance Use Disorders:
46% Expelled6
2 X Risk8 Absenteeism14
35% Drop Out6 Earlier Onset9 and reduced
Lower Occupational Status7 Less Likely to Quit Productivity14
in Adulthood10

1. DiScala et al., 1998. 6. Barkley, et al., 1990. 9. Pomerleau et al., 1995. 12. Brown & Pacini, 1989.
2. Liebson et al., 2001. 7. Mannuzza et al., 1997. 10. Wilens et al., 1995. 13. Mash & Johnston, 1983.
3. NHTSA, 1997. 8. Biederman et al., 1997. 11. Barkley, Fischer et al., 1991. 14. Noe et al., 1999.
4-5. Barkley et al., 1993; 1996.

Bipolar Disorder in Children


Difficulties in Diagnosing Pediatric Bipolar
Disorder

 Variability in clinical presentation
 Severity, phase of the illness (depressed, manic,
mixed, rapid cycling); and subtype of bipolar disorder
 Highly comorbid with other psychiatric disorders
 Effects of child’s development in symptom expression
 Child’s physical and behavioral problems may be
expressions of her or his symptoms
 Effects of medications
 Context where the bipolar disorder is developing


Developmental Manifestations of Manic Symptoms
in Children
 Elation/euphoria
 Giggling uncontrollably in class while peers are calm;
laughing hysterically when talking about killing others
 Dancing and laughing at home while telling parents’ they
are “suspended”
 Finds everything funny & they don’t know why
 Decreased need for sleep
 Up at 2 AM rearranging furniture, cleaning, then awake at
6 AM dressed and ready for school
 Child awake at 4 AM during summer vacation

Geller et al., American Journal of Psychiatry, 2002; 159: 927-933


Developmental Manifestations of Manic
Symptoms in Children (continued)
 Grandiosity
 Telling principal to “shut up” and listen because the principal is
the child’s “slave”; demanding that teacher be fired for stupidity
 Child stealing go-kart because he felt rules did not apply to him
(acute onset of conduct d/o)
 Child believing he/she is a superhero & tries to fly
 Child spends evenings “practicing” when they become
president, despite failing in school

 Hypersexuality – drawing or preoccupied with pictures of naked
people; inappropriate kissing, touching of others breasts/buttocks; 1-900-
sex lines; sexually vulgar language; sending notes propositioning peers


Frequent Prodromal Features Before Onset of BP-I
Ages 0-6 (n=13) Ages 7-10 (n=24) 11-12 (n=10)

Symptoms/Behaviors (%)
Cried -23% Irritable mood-29% Depressive
Increased Overly sensitive-25% mood-50%
energy-23% Cried-21% Low energy/tired-30%
Bold/Demanding-23% Bold /Demanding-21% Increased
Quick temper-15% energy-30%
Quick Temper-21%
Anxious-15% Labile/mood
Energy-17%
changes-30%
Anxious-30%
Cried-30%

Egeland et al., 2000


ADHD and Bipolar Disorder Are Highly
Co-morbid Conditions


Conditions That May Co-Exist with
Attention-Deficit/Hyperactivity Disorder


Reward Deficiency Syndrome or “Salience
Disruption Syndrome”


Reward Deficiency Syndrome or “Salience
Disruption Syndrome”
Addictive Impulsive Compulsive Personality
behaviour behaviour behaviour disorder
Attention deficit
Conduct
Alcoholism disorder + Aberrant disorder
hyperactivity sexual
Polysubstance Tourette’s behaviour Antisocial
abuse syndrome personality

Smoking
Pathological Aggressive
Autism
gambling behaviour
Obesity

Redrawn and adapted from Blum, K. et al., American Scientist 1996; 1-30
www.sigmaxi.org/amsci/Articles/96Articles/Blum-full.html


Bipolar
Disorder


Personality
Disorders Bipolar
Tourette’s
Disorder syndrome

ADHD Autism
spectrum
disorders
Conduct
disorders Anxiety
Disorders

Impulse Sexual Substance Eating
Control disorders/ Abuse Disorders
Disorders addictions


Irritable bowel Cardio-
Pain Fibromyalgia
syndrome vascular
Disorders

Obesity

Migraine

Diabetes
Mellitus

Personality
Disorders Bipolar
Tourette’s
Disorder syndrome

ADHD Autism
spectrum
disorders
Conduct
disorders Anxiety
Disorders

Impulse Sexual Substance Eating
Control disorders/ Abuse Disorders
Disorders addictions


Differentiating Bipolar Disorder and ADHD


Attention Deficit Disorder, Pediatric Bipolar
Disorder and Neurobehavioral Disorders

 ALL START IN CHILDHOOD
 Attention Deficit Hyperactivity Disorder
 ADHD starts before age seven
 Pediatric Bipolar Disorder
 Starts before puberty
 Neurobehavioral Disorders
 Often prenatal or perinatal in origin
 Initial symptoms start in early childhood



 Children with Attention-Deficit/Hyperactivity
Disorder are NOT more active in play
 ONLY when they are asked to stop and sit still
 Therefore, we see a diminished:
 Ability to INHIBIT activity
 Therefore: impulsive, hyperactive (immature)
 Ability to INHIBIT response to distractions
 Therefore: inattentive (not age appropriate)
 The brain’s “brake” is not working well


AD/HD - Co-existing Conditions:
Depression

35 % of individuals with AD/HD will have depression
50
45
40
35
30 Children
25
20 Adults
15
10
5
0


AD/HD - Co-existing Conditions:
Mania or Bipolar Disorder

 20% of individuals with AD/HD may manifest
bipolar disorder

 May have moods that change very rapidly,
seemingly for no reason


AD/HD - Co-existing Conditions: Anxiety
Disorders

35% of individuals with AD/HD will have anxiety.
40
35
30
25 Children
20
Adults
15
10
5
0


Bipolar Disorder - Differential Diagnoses

 Normal moodiness and behaviors
 Recurrent explosive, aggressive, and irritable
behaviors: Bipolar vs. unipolar recurrent agitated
MDD vs. ADHD + ODD
 Asperger’s Disorder
 ADHD vs. Bipolar
 Abrupt onset of “ADHD”
 Late onset “ADHD”
 Intermittent “ADHD”
 Intermittent worsening of the ADHD symptoms
( “tolerance” to the stimulants)
 In adolescents: Borderline Personality Disorder


Things That Look Like ADHD

 Depression  Learning disabilities
 Anxiety  Parenting problems
 Hearing problems  Substance use
 Visual problems  Medication side-effects
 Seizure disorder  Lead poisoning
 Oppositional defiant
disorder
 Autism


Diagnostic Overlap between Mania & ADHD

DSM-IV Mania ADHD

Elevated, expansive mood No
Irritability Commonly associated
Inflated self-esteem / grandiosity No
Decreased need for sleep Can be present

More talkative / pressured speech DSM-IV Criteria

Flight of Ideas or racing thoughts No
Hyperactivity / goal-directed activity DSM-IV Criteria
Pleasurable activities with high risk
Commonly associated
…for painful consequences
Distractibility DSM-IV Criteria


Pediatric Bipolar Disorder
 Bipolar (Manic Depressive) Disorder
 Pediatric Mania
 Hyperactive even in play
• ADHD normal during play
 Racing thoughts, rapid speech
• ADHD shows normal rate of cognition and speech
 Little need to sleep
• ADHD children may be too hyperactive to fall asleep
• But their need for sleep is otherwise normal
 Euphoria, grandiosity - unique to Mania


versus Mania

 Attention Deficit Hyperactivity Disorder = Poor “brakes”
 Cannot stop - in age appropriate manner
 Mania = Too much “acceleration”
 Brain is racing too fast
 Both may show:
 Hyperactivity, distractibility, irritability
 Mania shows severe mood swings:
 Elation, grandiosity, racing thoughts/speech


Keys to Differentiating Bipolar Disorder and Attention Deficit
Disorder
Bipolar Disorder ADD/ADHD

Most common onset ages 15-19 Present by K/G1 or Earlier

Family history of attentional problems but mood
Family history of mood disorder
disorders less commonly
Family history of alcohol or substance abuse
Family history of alcohol or substance abuse
less common
Fluctuating moods Fluctuating attention

Discrete mood episodes Chronic condition

Seasonality of symptoms No seasonal component

Premenstrual exacerbation of attentional
Hormonal exacerbation of mood disorders
problems

Daily variation in mood and activity Relatively fixed mood and activity level in the

Flight of Ideas or racing thoughts Accelerated thinking

Poor response to antidepressants Equivocal response to antidepressants

Symptoms often exacerbated by psychostimulants Symptoms usually improved by
psychostimulants

Children with Bipolar Disorder and Elation/
Grandiosity (n=93) vs. ADHD (n=81)
100

75

50

25

0

1 2 3 4 5 6 7 8 9

le
ed
ed

le
se

nt

ctib

y
ch
Ne
at

tab

erg
me
t
dio

igh
El

ee

tra
ep

dg

Irri
an

En
Fl

Sp

Dis
g/

Sle
Gr

Ju
cin
Ra

=BPD


Irritable Neurobehavioral Disordered
Children

 Irritability may be based on disorders of brain chemistry:
 Attention Deficit Hyperactivity Disorder, Bipolar
Disorder, Schizophrenia, etc.
 Or it may be a child with early brain damage from:
 Drugs or alcohol used in pregnancy
 Difficult or premature delivery
 Very early traumatic brain injury
 Genetic diseases
 Epileptiform disorders


Impulsive/Irritable
 Irritability = short fuse
 Early onset/persistent tantrums
 Impulsive behavior
 Impulsive aggression
 These behaviors are NOT premeditated
 Irritable behaviors are not planned
 Quick/hot temper = Poor impulse control and too much
emotion
 Differs from conduct disorders, some psychosis and
Psychopathy:
 In cold blood, premeditated, too little emotion


Relationship Between Conduct Disorder and
Bipolar Disorder
Symptom Profile of Bipolar Disorder

BPD = bipolar disorder; CD = conduct disorder.
Reprinted with perminssion, Biederman J et al. Biol Psychiatry. 2003;53:952-960 © 2003 Society of Biological Psychiatry.

Relationship Between Conduct Disorder and
Bipolar Disorder
Symptom Profile of Conduct Disorder

CD
BPD + CD

Reprinted with perminssion, Biederman J et al. Biol Psychiatry. 2003;53:952-960 © 2003 Society of Biological Psychiatry.

Comprehensive Treatment Strategies for
ADHD


Assessments

 Comprehensive clinical evaluation Check for IQ,
learning disabilities
 Check for other diagnoses
 Rule out Bipolar disorder, Neurocognitive
problems and other disorders
 ADHD rating scales
 Conners Scales for Teachers
 Neuropsychological testing
 Continuous Performance Test (CPT)


The Pharmacological Treatment of ADHD:
Stimulants and Others
Methylphenidate: Ritalin: 5-60mg; Concerta 18-81mg/day
Dextroamphetamine: Dexidrine SR: 5-15mg
Adderall XR: 4 amphetamine salts: 10-30mg
Pemoline: Cylert: 37.5mg/day, increase up to 75mg
Atomoxetine: Strattera (non-stimulant): 80-120mg
Others:
Modafinil: Provigil: 300mg
Buproprion: dopamine and norepinephrine reuptake inhibitor
Clonidine: α-adrenoceptor agonists: 0.1mg t.i.d.
(Guanfacine {Tenex}): α-adrenoceptor agonists: 1-3mg q.d.

ADHD: Treatment Types
 Medications: Essential to explain to the child - and adults -
that treatment must be year-round
 Integrated medical approaches:
 Nutrition
 Food additives
 Herbs and supplements including fish oils
 Homeopathy
 Acupuncture
 Parent Training – Positive Discipline
 BIP (Behavior Intervention Plan)
 Structure – routines, schedules

School supports

Treatment of Bipolar Disorder in Young
People


Treatment of Bipolar Disorder in Children

 Acute
 Maintenance (prevention of relapses and
recurrences)
 Treatment of mania, depression, rapid
cycling, mixed episodes, and sometimes
psychosis
 Tools:
 Medications
 Psychotherapy
 Life style management


Bipolar Disorder - Psychoeducation
• Symptomatology
• Etiology ( e.g., genetics)
• Treatment
• Prognosis
• Prevention (early signs of relapse/recurrence)
• Psychosocial Scars
• Stigma
• Mood and sleep hygiene
• Importance of year-long compliance


Pharmacological Treatment

 Mood Stabilizers
 Lithium
 Anticonvulsants
 Valproate (Depakote); carbamazepine (Tegretol);
oxcarbamazepine (Tryleptal); lamotrigine (Lamictal) etc.
 New antipsychotics
 Risperidone (Risperdal), olanzapine (Zyprexa);
quetiapine (Seroquel), ziprasidone (Geodon),
aripripazole (Abilify) etc.
 Antidepressants
 Selective Serotonin Reuptake Inhibitors
 Venlafaxine (Effexor), bupropion (Wellbutrim) etc.
 Others: benzodiazepines, fish oils etc.

N.B. None is indicated for use in people under the age of 18


Bipolar Disorder – Pharmacological
Treatment (Cont’)
• Very few studies in youth - mostly open label
• Response to acute treatment with mood
stabilizers (lithium, valproate (VPA),
carbamazepine (CBZ) approx. 40%-80%
• Small study showed that valproate + quetiapine
was better than valproate + placebo for children
with mania
• Open studies suggest that the “atypicals” alone or
in combination may be efficacious
• May need treatment with multiple medications


Psychosocial Treatments

 Family Focus Therapy (FFT)
 Cognitive Behavior Therapy (CBT)
 Interpersonal Psychotherapy (IPT)
 Interpersonal and Social Rhythms Therapy
(IPSRT)


Why Treat Adolescent Bipolar Patients with
Adjunctive Family Psychoeducation?

 Family psychoeducation is a powerful adjunct to
pharmacotherapy for adult bipolar patients
 Family factors are correlated with the course of recurrent
mood disorders in adults and children
 Early-onset mood and behavioral disturbances are
associated with a high familial loading for major affective
disorder
 Mood stabilizers can be difficult to dispense safely to
adolescents living in chaotic family environments


Family Expressed Emotion Status as a Predictor of
9-Month Clinical Outcome

15

Number of Patients
11

8

4

0

Low EE (7/13) High EE (9/10)
No Relapse Relapse
North

χ2(1) = 3.82, p=.05
Miklowitz DJ , et al. Arch Gen Psychiatry, 1988;45(3):225-231


Summary 1: ADHD


Summary 1: ADHD

 Attention Deficit Hyperactivity Disorder


Summary 1: ADHD

 A common childhood disorder


Summary 1: ADHD

 With many causes


Summary 1: ADHD

 Often genetic (e.g. DAT-1, DRD2, D4 genes)


Summary 1: ADHD

 Can produce serious life distress


Summary 1: ADHD

 Learning, behavior, social, teen safety


Summary 1: ADHD

 Goal is to create resilience:


Summary 1: ADHD

 Goal is to create resilience:
 Positive discipline, structure, medications


Summary 2: Bipolar Disorder



• BP disorder in youth is a chronic and difficult to treat
illness that conveys high morbidity (e.g., behavior
problems, substance abuse), poor psychosocial
functioning, psychosis, and risk for suicide



• Youth with BP usually have mixed and rapid cycling
patterns that are the types carrying the worst prognosis
and are more difficult to treat



• BP is highly comorbid with other psychiatric disorders
that require identification and treatment



• BP is highly comorbid with other psychiatric disorders
that require identification and treatment
• The diagnosis of BP may be difficult and requires
longitudinal follow-up


Summary 3

 The treatment of both ADHD and bipolar disorder
requires four attention to four factors:
 Physical:
 Appropriate medications
 Nutrition

 Environmental factors

 Psychological
 Social
 Spiritual


Useful Addresses


www.RichardGPettyMD.com


www.RichardGPettyMD.blogs.com


rpettyus@aol.com


www.Healia.com


ADHD Bipolar Disorder

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