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30.Wk9Dis

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Review this week’s Learning Resources and reflect on the insights they provide.

Go to the Stahl Online website and examine the case study you were assigned.

Take the pretest for the case study.

Review the patient intake documentation, psychiatric history, patient file, medication history, etc. As you progress through each section, formulate a list of questions that you might ask the patient if he or she were in your office.

Based on the patient’s case history, consider other people in his or her life that you would need to speak to or get feedback from (i.e., family members, teachers, nursing home aides, etc.).

Consider whether any additional physical exams or diagnostic testing may be necessary for the patient.

Develop a differential diagnoses for the patient. Refer to the DSM-5 in this week’s Learning Resources for guidance.

Review the patient’s past and current medications. Refer to Stahl’s Prescriber’s Guide and consider medications you might select for this patient.

Review the posttest for the case study.

Table B. KQ2: Long-term (>1 year) effectiveness of interventions for ADHD in people 6 years and

older
Conclusion

Medication Treatment

Level of EvidenceIntervention
SOE: Low Very few studies include untreated controls.

Studies were largely funded by industry.
SMD: -0.54 (95%
Cl, -0.79 to -0.29)

MPH:

Psychostimulants continue to provide control of ADHD
symptoms and are generally well tolerated for months to years

ATX: at a time. The evidence for MPH use in the context of careful
SMD: -0.40 (95% medication monitoring shows good evidence for benefits for
Cl, -0.61 to -0.18) symptoms for 14 months.

ATX is effective for ADHD symptoms and well tolerated over 12
months.

SOE: Insufficient Only one study of GXR monotherapy is available. It reports
reduced ADHD symptoms and global improvement, although
less than a fifth of participants completed 12 months.

Monitoring of cardiac status may be indicated since
approximately 1% of participants showed EGG changes judged
clinically significant.

Combined The results from 2 cohorts indicate both medication (MPH) and
Psychostimulant

SOE: Low
combined medication and behavioral treatment are effective in

Medication and SMD: -0.70 (95% treating ADHD plus ODD symptoms in children, primarily boys
Behavioral ages 7-9 years of nomnal intelligence with combined type of
Treatment

Cl, -0.95 to -0.46)
ADHD, especially during the first 2 years of treatment.

Several reports from one high-quality study suggest that
combined medication and behavioral treatment improves
outcomes more than medication alone for some subgroups of
children with ADHD combined type and for some outcomes.

Behavioral/ There is not enough evidence to draw conclusions for persons
Psychosocial

SOE: Insufficient

6 years and older with a diagnosis of ADHD.

Parent Behavior There is not enough evidence to draw conclusions for persons
Training

SOE: Insufficient
6 years and older with a diagnosis of ADHD.

Academic Interventions One good-quality study and its extension showed that
classroom-based programs to enhance academic skills are
effective in improving achievement scores in multiple
domains, but following discontinuation, the benefits for
sustained growth in academic skills are limited to the domain
of reading fluency. All other domains show skill maintenance
but not continued growth.

SOE: Insufficient

..
Note: ADHD- attention defictt hyperactlvtty dtsorder, ATX- atomoxetine, ECG- electrocardiOgram, GXR- guanfacme
extended release; KQ =Key Question; MPH= methylphenidate; ODD= oppositional defiant disorder; SMD =standardized
mean difference; SOE =strength of evidence.

ES-15

Pharmacological Interventions
Multiple short-term studies document that psycho stimulant medications, either MPH,

dextroamphetamine (DEX), or mixed amphetamine salts (MAS), effectively decrease the core
symptoms of ADHD and associated impairment. 10 A review of the mechanisms of action of
pharmacological interventions for ADHD is beyond the scope of this report. Some preparations
last only a few hours, with symptoms returning as the medication wears off. Many families
choose to use medication primarily on school days, and these medications have primarily been
studied in school-aged children and youth aged 6 years and older. Psychostimulants, most
connnonly MPH and DEX, are generally safe and well tolerated. Common side effects include
poor appetite, insomnia, headaches, stomachaches, and increased blood pressure and heart rate.
Prolonged use may result in a decreased rate of growth, generally considered clinically
insignificant.n 8 Concerns have been raised from postmarketing surveillance suggesting a rare
incidence of sudden death, perhaps associated with pre-existing cardiac defects, however, the
rate does not appear to exceed that of the base rate of sudden death in the population. 118 As noted
earlier, approximately 2.5 million children in the United States, ages 4 to 17 years with a
diagnosis of Attention Deficit Disorder (ADD) or ADHD, cunently take medication.

Several extended release preparations of psychostimulants have been developed in recent
years aimed at improved adherence and symptom control throughout the day as well as
decreased abuse potential. 120 Non-stimulants (e.g., alpha adrenergic agents and atomoxetine
(A TX)) have also been developed and found to be helpful in controlling symptoms with few
adverse events. 121 However, in general, the benefits of medications wear off when they are
discontinued. Since ADHD is a chronic disorder, many children, teens, and adults stay on
medications for years at a time. Given the possibility of cumulative effects over time, a review of
evidence regarding benefits and risks of prolonged medication use for ADHD is indicated.

Nonpharmacological Interventions
In the area of nonpharmacologic interventions, behavior training has been found to be

helpful, primarily for disruptive behaviors that frequently coincide with ADHD. 122 Since ADHD
may begin before school age, using the precedent of older children, increasing numbers of
preschoolers are being identified and treated, sometimes with medications. However, the most
commonly used psychostimulant, MPH, does not yet have government regulatory approval for
use in children less than 6 years of age, while MAS has been granted aEproval by the FDA in the
United States for children under 6 years, but older than 3 years of age. 2 Recent reviews of
treatments for preschoolers with ADHD emphasize the use of parenting interventions prior to
medication based on general clinical consensus. 124 Indeed, the Preschool ADHD Treatment
Study (PATS), funded by the U.S. National Institute for Mental Health (NIMH), included parent
behavior training (PBT) as the first phase for all children recruited into the study prior to
randomization for the purpose of evaluating efficacy and safety of psychostimulant
medication. 125 While the few studies available suggest stimulant medications are effective for the
core symptoms of inattention, hyperactivity, and impulsiveness in very young children,
psychostimulants also appear to cause more adverse events in preschool children than in older
children. 54 Beyond the PATS, little information exists to document effectiveness of either
medication or non-medication interventions specifically for ADHD in this age group. Part of the
difficulty has been lack of clarity regarding reliability and validity of diagnostic criteria and
therefore lack of widespread application of the ADHD diagnosis for children under 6 years.n 9

PATIENT FILE

133

PATIENT FILE
The Case: 8-year-old girl who was naughty

The Question: Do girls get ADHD?

The Psychopharm Dilemma: How do you treat ADHD with oppositional

symptoms?

Pretest Self Assessment Question (answer at the end of the case)

What is true about oppositional symptoms in patients

with ADHD

A. They can be part of the diagnostic criteria for ADHD in children
B. They can be confused with impulsive symptoms of ADHD
C. They can be part of oppositional defi ant disorder (ODD) which can be

comorbid with ADHD
D. They can be part of conduct disorder (CD) which can be comorbid

with ADHD

Patient Intake
• 8-year-old girl brought to her pediatrician by her 26-year-old mother
• Chief complaint: fever and sore throat

Psychiatric History
• While evaluating the patient for an upper respiratory infection, the

pediatrician asks if school is going well
• The patient responds “yes” but in the background the mother shakes

her head “no”
• The mother states that her daughter is negative and defi ant at home

and she has similar reports, mostly of disobedience, from her teacher
at school

• The patient has had temper tantrums since age 5 but these have
decreased over the past 3 years, especially the past year

• Still angry and resentful since her little sister was born 6 years ago
• Academic problems
• Fights with other children, mostly arguments and harsh words with

other girls at school

Social and Personal History
• Goes to public school
• Has a younger sister age 6
• Does not see her father much, lives in a nearby city
• Not many friends
• Spends most of her time with her sister and either her mother or her

maternal grandmother who helps with after school supervision and
baby sitting

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PATIENT FILE

134

Medical History
• None

Family History
• None known for medical or psychiatric disorders other than the father

who drinks a bit too much and his father (paternal grandfather) who
some think might be an alcoholic

• Mother was adopted and no family history known

Pediatrician’s Notes: Initial Evaluation
• Not enough time to do any more evaluation
• Instead, the mother is given the parent and teacher version of the

Conners ADHD rating scale and is instructed to bring the completed
forms to the followup visit

• A variety of rating scales are available, some without charge (see
http://www.neurotransmitter.net/adhdscales.html).

• The Connors scale charges a fee but other rating scales available at
this link, or listed in the Two-Minute Tute below are free.

Pediatrician’s Notes: Followup Visit Week 3
• At the followup visit, the mother admits to having been too busy to fi ll

out the parent form
• Also admits to having forgotten to send the rating form to the teacher
• Mother acknowledges being more disorganized since her second

child started school this year
• Since then it has also been extremely diffi cult to keep the patient

organized and focused on school
• The mother is on the verge of tears
• “Two children are too much for a single mother”
• The pediatrician offers to send the teacher form to the school and

gives the mother tips on how to remember to fi ll out her own form
• When the teacher form is sent back to the pediatrician’s offi ce the

mother will be contacted for a followup visit

Pediatrician’s Notes: Followup Visit Week 6
• At the followup visit, the mother comes alone
• Teacher’s ADHD rating scale responses state that the patient has

signifi cant problems with
– Talking excessively
– Sustaining attention
– Being organized
– Being distracted
– Being forgetful

PATIENT FILE

135

– Following instructions
– Making careless errors (except when it comes to her homework)

• The teacher also complains of the patient being more argumentative and
disobedient than the other children in her class

• The mother’s responses on the ADHD rating scales are similar to the
teacher’s but she endorses only fi ve symptoms as signifi cantly impairing

• Checked “severe” for ability to listen (rated only mild by the teacher)
• Upon further questioning by the pediatrician, it becomes clear that the

mother is compensating for her daughter by
– Double checking her homework
– Making sure homework is in her backpack
– Helping the patient be organized

• Eventually, symptoms that were originally determined to be “mild” by the
mother are changed to “signifi cantly impairing”

• Mother confi rms that the patient argues a lot with her, especially when
the mother is trying to oversee her work, and that the patient still
occasionally has temper tantrums similar to when she was fi ve years
old, but milder

Based on just what you have been told so far about this patient’s history

what do you think is her diagnosis?

• ADHD
• ODD (oppositional defi ant disorder)
• CD (conduct disorder)
• ADHD comorbid with ODD
• ADHD comorbid with CD
• A child acting out again her mother’s divorce and against having to

share her mother with her sister
• Other

Pediatrician’s Mental Notes: Followup Visit, Week 6, Continued
• The patient is diagnosed with ADHD, mostly inattentive type,

comorbid with symptoms of oppositional defi ant disorder
– ADHD symptoms include inattention but not hyperactivity
– Some of her impulsive symptoms such as being argumentative

and disobedient overlap with her ODD symptoms but the ODD
symptoms seem to be willful and on purpose rather than truly
thoughtlessly impulsive

• To be diagnosed with conduct disorder, the patient would need to
exhibit symptoms similar to ODD plus have aggression towards
animals, destruction of property, deceitfulness or theft, and serious
violations of rules, symptoms of a type and severity that neither the
teacher nor the mother brought up

PATIENT FILE

136

How would you treat her?

• Cognitive behavioral therapy
• Parent training
• d-methylphenidate XR (Focalin) 5 mg once daily in the morning

titrated in 5 mg increments each week to optimization
• OROS methylphenidate (Concerta) 18 mg once daily in the morning

titrated in 18 mg increments each week to optimization
• Mixed salts of amphetamine XR (Adderall XR) 10 mg once daily in the

morning titrated in 10 mg increments each week to optimization
• Lisdexamfetamine (Vyvanse) 30 mg once daily in the morning titrated

in 10–20 mg increments a week to optimization

• Other

Pediatrician’s Mental Notes: Followup Visit Week 6, Continued
• Mother is initially uncomfortable with the diagnosis of ADHD with

ODD and is far from ready to accept medication treatment for her
daughter

• Wants different options
• Pediatrician suggests cognitive behavioral therapy and parent

training
• Pediatrician also offers to write a letter to the school to implement

strategies to help her daughter such as
– Allowing extra time on tests and assignments
– Placing child nearest to the teacher
– Devising signals between teacher and child to redirect child’s

attention without embarrassing the child

Pediatrician’s Mental Notes: Followup Visit Week 10
• Mother learns that closest CBT specialist is one-hour drive away from

their home so this option falls through
• Also, while the teacher is happy to implement the strategies

suggested by the pediatrician, she admits to already using them with
the patient, given her experience with other ADHD students

• The lack of non-pharmacological treatment options helps the mother
reconsider the risks versus the benefi ts of ADHD medications

• All the options listed as stimulants in the list above, plus some
nonstimulants, are approved for the treatment of ADHD and have
shown some effi cacy for ODD symptoms

• D-methylphenidate XR is chosen

Pediatrician’s Mental Notes: Followup Visits Weeks 12 and 14
• The dose of d-methylphenidate is titrated to 20 mg/day with some

improvement in classroom behavior according to the teacher

PATIENT FILE

137

• However, the patient develops problems with initial insomnia
– Sometimes the effects of stimulants later in the day can actually

improve sleep, especially in hyperactive individuals who have
problems slowing down for bedtime routines

– Some studies suggest that OROS methylphenidate lasts even
longer (up to 12 hours) compared to d-methylphenidate XR,
which seems to be more effective in the fi rst 8 hours; thus OROS
methylphenidate would be a potential option in such cases

– However, this is not this patient’s presentation
– Since this patient did not have problems with sleep prior to

starting d-methylphenidate XR, the initial insomnia is likely due to
the stimulant

• Also, even though classroom behavior seems to be improving
according to the teacher, the patient remains defi ant with the mother,
tears up some toys of her younger sister to upset her and screams
more than ever at her mother while doing homework, seeming
delighted when her mother gets upset and yells back

• The mother is instructed to give the medication another month to see
if the improvements in the classroom begin to be seen in the home
and is instructed about sleep hygiene including

– Keeping regular schedules for going to bed and waking up
– Avoiding the patient’s favorite caffeinated sodas, especially in the

late afternoon
– Providing quiet activities as part of a bedtime routine
– Having the patient leave her room to do another quiet activity if she

does not fall asleep within 30 minutes

Pediatrician’s Mental Notes: Followup Visit Week 18
• The mother herself is often overwhelmed and disorganized and so

has a diffi cult time keeping regular schedules for going to bed and
waking up, even during the week but especially on weekends

• Despite trying the behavioral approach, the initial insomnia remains a
problem

• So does the defi ant behavior at home
• Also, reports last week that the patient shoved somebody who she

said was crowding in line, causing her classmate to cut her knee,
requiring stitches/sutures

• Was not sorry or remorseful

How would you treat her now?

• Refer to a psychiatrist for further evaluation and
psychopharmacological management

• Refer to a psychologist for therapy

PATIENT FILE

138

• Switch to dl-methylphenidate immediate release (classical Ritalin) 10
mg twice daily, then titrate to optimized dose

• Switch to the methylphenidate transdermal patch (Daytrana) starting
at 10 mg, then titrate to optimized dose

• Switch to the prodrug lisdexamfetamine (Vyvanse) starting at 30 mg
once in the morning, then titrate to optimized dose

• Switch to atomoxetine (Strattera) 10–18 mg per day, then titrated to
optimized dose

• Switch to guanfacineXR (Intuniv) 1 mg/day, then titrated to optimized
dose

• Other

Pediatrician’s Mental Notes: Followup Visit Week 18, Continued
• Each treatment option has specifi c considerations to take into account:

– In general, the active d enantiomer of methylphenidate (which
the patient was originally prescribed) may be slightly more
than twice as potent as racemic d,l-methylphenidate; so, if side
effects persist on d-methylphenidate it may be useful to switch
to immediate release d, l methylphenidate which might require a
“sculpted dose” with a higher morning than afternoon dose

– The methylphenidate patch needs to have the patient and mother
follow instructions and in this patient’s case, may need to remove
the patch before the suggested nine-hour wear time is over, if
insomnia or other adverse events emerge; the patch should not be
cut as a way to lower the dose

– Lisdexamfetamine should be titrated by increasing the dose in
10–20 mg increments each week; 10–12 hours of clinical action
can be expected, so might be less favorable in patients who
already have problems with insomnia

– Atomoxetine can have a longer onset of action but does not cause
insomnia

– Guanfacine/guanfacineXR should start at 1 mg and titrate by 1 mg
increments to a maximum of 4 mg/day but an 8 year old will not
likely need or tolerate the highest dose, which may cause sedation

• The mother prefers the methylphenidate patch approach, as it seems
to be the most convenient way to address the sleep problems

• Additionally, sometimes the patient refuses to swallow pills and will
take the medication only if convinced to do so, or possibly if sprinkled
on food. This confrontation over medications adds too much extra
time to the mother’s already hectic morning schedule

• The patient likes the novelty of the patch, which reminds her of a
sticker

PATIENT FILE

139

Pediatrician’s Mental Notes: Followup Visit Week 20
• The 10 mg patch with an eight hour or shorter wear time addresses

the classroom ADHD symptoms without causing insomnia
• However, on the days when the mother forgets to remove the patch

before 3 pm, insomnia returns
• That is resolved by setting her cell-phone alarm to remind her to

remove the patch every day at 3 pm after applying it at 7 am
• At fi rst the patient and her mother are impressed with the novelty of

the patch and its fl exibility and the resolution of the patient’s insomnia
• However, she is still argumentative, including some evenings at

bedtime, and this can interfere with getting to bed on time even
though the patient no longer has insomnia

• The patient scratched her sister’s face last week with her fi ngernails
because her sister was playing with the patient’s dolls

• Thinks it is funny that her sister’s face is scratched
• “She looks like she has warpaint on her cheek”
• The pediatrician feels like only a bit of progress has been made with

several months of medication treatment, including two different
stimulants

• Even though inattentive symptoms in the classroom are reportedly
improved, oppositional symptoms both at school and at home are not
improved and if anything, are the main problem now

• Furthermore, the patches are expensive, not covered well by the
mother’s insurance and frequently are pulled off by the patient or her
classmates tormenting her in response to her fi ghting/arguing with
them

• Refers the patient and her mother to a psychiatrist

Attending Psychiatrist’s Mental Notes: Initial Psychiatric
Evaluation
• Seems like the patient needs more stimulant during the day and less

at night
• Also, seems like the oppositional symptoms may require special

therapeutic focus
• Considerations include:

– Developing a platform of stimulant to optimize treatment with
another oral medication

– Increasing the dose during the day to see if oppositional
symptoms will respond to this

– If not, consider augmentation strategies for the oppositional
symptoms

– Psychotherapy (too expensive and too time consuming, mother
cannot miss work, and too far away)

PATIENT FILE

140

– Atypical antipsychotic (controversial, for use of atypical
antipsychotics is not approved for ADHD or for oppositional
symptoms of ADHD/ODD

– guanfacine XR – approved for ADHD with some evidence
for use in oppositional as well as inattentive/hyperactive
symptoms of ADHD but not approved for ODD

• Suggested switching back to an oral medication from the patch
• Trial of lisdexamfetamine 30 mg once in the morning

Attending Physician’s Mental Notes: First and Second Interim
Followups, Weeks 4 and 8
• Only partial effi cacy but no insomnia
• Rather than increase dose of lisdexamfetamine, added 5 mg of

dextroamphetamine at 7 am, then 10 mg, then 15 mg, became
nauseous, reduced to 10 mg on top of lisdexamphetamine 30 mg in
the morning

• Sometimes a second 5 mg dose of the dextroamphetamine after
school is necessary

• This regimen does not cause insomnia
• ADHD better but oppositional symptoms persist
• Augmentation with guanfacine XR 1 mg/day

Case Outcome: Followup Weeks 12 to 20
• No side effects
• Titration to 2 mg/day
• Continues lisdexamfetamine 30 mg in the morning
• Plus dextroamphetamine 5 mg in the morning
• Plus occasional dextroamphetamine 5 mg additional daytime dose
• Oppositional symptoms improved slowly but surely over 2 months
• Psychiatrist asks whether the patient’s sister has any problems

in school, and the mother states that she is “spacey” but not
oppositional

• Psychiatrist suggests to bring in the sister the next time the patient
comes and gives mother screening forms for ADHD and asks her
to consult with her other daughter’s teacher to see if there are
symptoms of ADHD in that daughter as well

• Psychiatrist asks mother to make an appointment for herself because
it is obvious that she has undiagnosed and untreated ADHD

– Given adult ADHD rating form for mother to fi ll out
– Symptoms of ADHD in the mother are obvious during various

interviews
– Mother misses appointments or is late for appointments
– Often appears disorganized

PATIENT FILE

141

– Did not fi ll out her child’s forms on time
– Did not deliver forms to her child’s teacher, forgot, lost them
– Admits being very disorganized since her second child started

school
– Feels overwhelmed by two children and her life circumstances
– Could also have some signs of depression
– Can’t get organized to take her child to CBT
– Has a hard time keeping a regular schedule and also keeping her

daughter on a regular schedule of going to bed and waking up
– Was unable to remember to remove the daughter’s skin patch

unless she set a cell phone alarm
– All these suggest further evaluation of the mother is indicated

since ADHD commonly runs in families and has a very high
genetic contribution

– See the following Case 14, p 151 for presentation of the
mother’s case

Case Debrief
• The patient is an 8-year-old with ADHD, inattentive type with

comorbid ODD
• High doses of stimulants reduce inattention but cause insomnia and

do not adequately treat oppositional symptoms
• “Top up” with the alpha 2A selective noradrenergic agonist

(guanfacine XR) improves oppositional symptoms and the patient has
stabilized

Take-Home Points
• ADHD with ODD comorbidity can be a diffi cult combination of

behaviors to treat in children
• Combining stimulants with alpha 2A selective agonist actions may

be useful in some patients with this combination of symptoms not
adequately responsive to stimulants alone

Performance in Practice: Confessions of a
Psychopharmacologist
• What could have been done better here?

– Should the father have been included in the medical decisions?
– Whether or not he has legal medical rights, he has visitation rights

and could feel upset or vindictive if left out
– It is possible that the patient is still dealing with her parents’

divorce and still adjusting to her sister taking some of her
mother’s time and attention; some of the oppositional symptoms
may not be due to ODD but to family confl ict and possibly family

PATIENT FILE

142

or individual psychotherapy involving the patient, her mother and/
or her sister could be productive here

• Possible action item for improvement in practice
– Make a concerted effort to involve the father
– Perhaps this patient should have been sent to a specialist

psychopharmacologist earlier and symptom improvement may
have occurred earlier

– Perhaps a trial of atomoxetine would have been benefi cial

Tips and Pearls
• Although guanfacine XR is approved as a monotherapy for ADHD,

some studies and clinical anecdotes suggest that it can be combined
with stimulatnts for patients with diffi cult oppositional comorbid
symptoms

• “Sculpted therapy” combining long acting with immediate acting
formulations of stimulants may optimize treatment for some cases
with inadequate responses to long acting formulations alone

Two-Minute Tute: A brief lesson and psychopharmacology
tutorial (tute) with relevant background material for this case
– Rating scales
– Oppositional Defi ant Disorder vs Conduct Disorder
– NE and DA in prefrontal cortex in ADHD

Table 1: ADHD Rating Scale-IV – home version

Child’s Name __________________________________________________

Child’s Age ______ Sex: M F Grade______ Child’s Race______

Completed by: Mother Father Guardian Grandparent

Circle the number that best describes your child’s home behavior over the
last 6 months

never sometimes often very
or rarely often

1. Fails to give close attention

to details or makes careless

mistakes in schoolwork. 0 1 2 3

2. Fidgets with hands or feet or

squirms in seat. 0 1 2 3

3. Has diffi culty sustaining

attention in tasks or play

activities. 0 1 2 3

4. Leaves seat in classroom or

in other situations in which

remaining seated is expected. 0 1 2 3

PATIENT FILE

143

5. Does not seem to listen

when spoken to directly. 0 1 2 3

6. Runs about or climbs

excessively in situations in

which it is inappropriate. 0 1 2 3

7. Does not follow through on

instructions and fails to fi nish

work. 0 1 2 3

8. Has diffi culty playing or

engaging in leisure activities

quietly. 0 1 2 3

9. Has diffi culty organizing tasks

and activities. 0 1 2 3

10. Is “on the go” or acts as if

“driven by a motor.” 0 1 2 3

11.A voids tasks (e.g., schoolwork,

homework) that require

sustained mental effort. 0 1 2 3

12.T alks excessively 0 1 2 3

13. Loses things necessary for

tasks or activities. 0 1 2 3

14. Blurts out answers before

questions have been

completed. 0 1 2 3

15. Is easily distracted. 0 1 2 3

16. Has diffi culty awaiting turn. 0 1 2 3

17. Is forgetful in daily activities. 0 1 2 3

18. Interrupts or intrudes

on others. 0 1 2 3

PATIENT FILE

144

Table 2: ADHD rating scale-IV – school version

Child’s Name __________________________________________________
Child’s Age ______ Sex: M F Grade______ Child’s Race______
Completed by: Mother Father Guardian Grandparent

Circle the number that best describes your child’s home behavior over
the last 6 months

never sometimes often very
or rarely often

1. Fails to give close attention
to details or makes careless
mistakes in schoolwork. 0 1 2 3
2. Fidgets with hands or feet
or squirms in seat. 0 1 2 3
3. Has diffi culty sustaining
attention in tasks or play
activities. 0 1 2 3
4. Leaves seat in classroom or
in other situations in which
remaining seated is expected. 0 1 2 3
5. Does not seem to listen when
spoken to directly. 0 1 2 3
6. Runs about or climbs
excessively in situations in
which it is inappropriate. 0 1 2 3
7. Does not follow through on
instructions and fails to fi nish
work. 0 1 2 3
8. Has diffi culty playing or
engaging in leisure activities
quietly. 0 1 2 3
9. Has diffi culty organizing
tasks and activities. 0 1 2 3
10. Is “on the go” or acts as if
“driven by a motor.” 0 1 2 3
11. Avoids tasks (e.g., schoolwork,
homework) that require
sustained mental effort. 0 1 2 3
12. Talks excessively 0 1 2 3
13. Loses things necessary for
tasks or activities. 0 1 2 3
14. Blurts out answers before
questions have been
completed. 0 1 2 3
15. Is easily distracted. 0 1 2 3
16. Has diffi culty awaiting turn. 0 1 2 3
17. Is forgetful in daily activities. 0 1 2 3
18. Interrupts or intrudes on
others. 0 1 2 3

PATIENT FILE

145

Table 3: Oppositional defi ant disorder

• Aggressiveness

• Tendency to purposefully bother and irritate others

• Negativistic, hostile and defi ant behavior lasting at least 6 months
which according to DSM IV must have 4 or more of the following:

– Often loses temper

– Often argues with adults

– Often actively defi es or refuses to comply with adults’ requests

or rules

– Often deliberately annoys people

– Often blames others for his or her mistakes or misbehavior

– Is often touchy or easily annoyed by others

– Is often angry and resentful

– Is often spiteful and vindictive

Table 4: Conduct disorder

• Some think that conduct disorder is a worse version of ODD

• Approximately 6–10% of boys and 2–9% of girls

• Can be comorbid with ADHD

• Can go away by adulthood

• Can progress into antisocial personality disorder

• Can be comorbid with many other disorders including substance
abuse

• Violation of basic rights of others and rules of society, which
according to DSM IV at least three of the following must be
present in the last 12months and at least one in the last 6 months

– Aggression to people and animals
– Destruction of property
– Deceitfulness or theft
– Serious violations of rules

PATIENT FILE

146

P
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NE concentration

NE low-signal enhanced

DA low-noise increased

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DA concentration

Figure 1. ADHD: Hypothetically Low Signals and/or High Noise in the
Prefrontal Cortex (PFC) in ADHD.
Theoretically, ADHD with inattention, hyperactivity and/or impulsiveness
is due to the prefrontal cortex being “out of tune” with both DA
(dopamine) and NE (norepinephrine) being too low, and causing signals
to be low and/or “noise” to be too high and drown out signals, thus
creating the symptoms of ADHD

P
P
C
s
tr
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n
g
th
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f o
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tp
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NE concentration

NE optimized-signal increased

DA optimized-noise reduced

P
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DA concentration

Figure 2. ADHD: Treatment to Increase NE, Increase DA.
Stimulants increase both NE (norepinephrine) and DA (dopamine) actions
in prefrontal cortex, increasing signals and reducing noise and thus
hypothetically reducing the symptoms of ADHD

P
P
C
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th
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DA concentration

NE low-signal reduced

DA optimized-noise reduced
NE concentration

Figure 3. ADHD: Hypothetically Low Signals Due to Low NE.
Although many cases of ADHD may be due to low DA and NE as shown
in Figure 1, some may hypothetically be due to only low NE

PATIENT FILE

147

P
P
C
s
tr
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n
g
th
o
f o
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tp
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NE concentration
NE optimized-signal increased
DA optimized-noise reduced
P
P
C
s
tr
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n
g
th
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f o
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tp
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DA concentration

Figure 4. ADHD: Treatment with Alpha 2A Agonist.
In cases where ADHD is due predominantly to low NE activity, as shown
in Figure 3, selective NE enhancing agents such as the alpha 2A selective
noradrenergic agonist guanfacine XR may be helpful in treating ADHD
symptoms without necessarily needing to interact with DA

P
P
C
s
tr
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g
th
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tp
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NE concentration

NE very low-signal much reduced

DA low-noise increased
P
P
C
s
tr
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th
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DA concentration

Figure 5. ADHD and Oppositional Symptoms: Hypothetically Very Low
Signals in VMPFC (Ventromedial Prefrontal Cortex).
Cases of ADHD with comorbid ODD (oppositional defi ant disorder) may
differ from classical ADHD shown in Figure 1. With ADHD and ODD,
there may hypothetically be very low NE signals and low DA levels with
increased noise.

P
P
C
s
tr
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g
th
o
f o
u
tp
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NE concentration

NE still low-signal still reduced

DA optimized-noise reduced
P
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th
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DA concentration

Figure 6. ADHD and Oppositional Symptoms: Treatment with a Stimulant.
When ADHD with ODD (Figure 5) is treated with a stimulant, this
improves both NE and DA levels, but is theoretically suboptimal tuning
of NE. Thus, NE is still low, signals still reduced while DA optimized
because noise is reduced. This may explain why stimulants can improve
some ADHD symptoms in patients with comorbid ADHD but not their
ODD symptoms. Raising the dose of the stimulant would put NE into
balance, but would put DA too high and thus out of balance

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148

P
P
C
s
tr
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f o
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NE concentration
NE optimized-signal increased
DA optimized-noise reduced
P
P
C
s
tr
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n
g
th
o
f o
u
tp
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DA concentration

Figure 7. ADHD and Oppositional Symptoms: Augment a Stimulant with
an Alpha 2A Agonist.
After treatment of ADHD comorbid with ODD (Figure 5) with stimulants
(Figure 6), the prefrontal cortex is still not adequately tuned (Figure 6),
so that ADHD symptoms may be improved but oppositional symptoms
persist. Adding an alpha 2A selective noradrenergic agonist such as
guanfacine XR to the stimulant will improve NE tone selectively, and
hypothetically enhance the therapeutic actions of the stimulant so that
both ADHD and ODD symptomst are improved

Posttest Self Assessment Question: Answer
What is true about oppositional symptoms in patients with ADHD

A. They can be part of the diagnostic criteria for ADHD in children
– False. The diagnostic criteria are inattentive, hyperactive and

impulsive, not oppositional; some patients have oppositional
symptoms insuffi cient to meet the criteria for ODD but they are not
part of the diagnostic criteria for ADHD

B. They can be confused with impulsive symptoms of ADHD
– True. Oppositional symptoms, however, are purposeful and

without remorse whereas impulsive symptoms are thoughtless
and cause remorse after the fact

C. They can be part of oppositional defi ant disorder (ODD) which can be
comorbid with ADHD

– True
D. They can be part of conduct disorder (CD) which can be comorbid

with ADHD
– Although true, oppositional symptoms are not suffi cient for the

diagnosis of conduct disorder which requires additional symptoms
as well for the diagnosis to be made

Answer: B, C and D

References
1. Franke B, Neale BM, and Faraone SV. Genome-wide association

studies in ADHD. Hum Genet 2009; 126(1): 13–50
2. Haberstick BC, Timberlake D, Hopfer CJ et al. Genetic and

environmental contributions to retrospectively reported DSM-IV

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childhood attention defi cit hyperactivity disorder. Psychol Med 2008;
38(7): 1057–66

3. McLoughlin G, Ronald A, Kuntsi J et al. Genetic support for the
dual nature of attention defi cit hyperactivity disorder: substantial
genetic overlap between the inattentive and hyperactive-impulsive
components. J Abnorm Child Psychol 2007; 35(6): 999–1008

4. Todd RD, Rasmussen ER, Neuman RJ et al. Familiality and
heritability of subtypes of attention defi cit hyperactivity disorder in
a population sample of adolescent female twins. Am J Psychiatry
2001; 158(11): 1891–8

5. Faraone SV, Advances in the genetics and neurobiology of attention
defi cit hyperactivity disorder, Biol Psychiatry 2006; 60: 1025–7

6. Stahl SM, Stahl’s Illustrated Attention Defi cit Hyperactivity Disorder,
Cambridge University Press, New York, 2009

7. Stahl SM, Attention Defi cit Hyperactivity Disorder and its Treatment,
in Stahl’s Essential Psychopharmacology, 3rd edition, Cambridge
University Press, New York, 2008, pp 863–98

8. Stahl SM, Lisdexamfetamine, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 271–6

9. Stahl SM, Atomoxetine, in Stahl’s Essential Psychopharmacology
The Prescriber’s Guide, 3rd edition, Cambridge University Press,
New York, 2009, pp 51–5

10. Stahl SM, Guanfacine XR, in Stahl’s Essential Psychopharmacology
The Prescriber’s Guide, 3rd edition, Cambridge University Press,
New York, 2009, pp 233–5

11. Stahl SM, d-Methylphenidate, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 323–7

12. Stahl SM, d,l Methylphenidate, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 329–35

13. Stahl SM, Mixed Salts of d,l amphetamine, in Stahl’s Essential
Psychopharmacology The Prescriber’s Guide, 3rd edition,
Cambridge University Press, New York, 2009, pp 39–44

14. Stahl SM, d-amphetamine, in Stahl’s Essential Psychopharmacology
The Prescriber’s Guide, 3rd edition, Cambridge University Press,
New York, 2009, pp 33–8

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