TDAH Flashcards
QUESTION ONE
Peter, a 35-year-old stockbroker, has been advised by his supervisor
to come and see you, the company mental health consultant. His
supervisor is complaining that he often comes to appointments
late, is inappropriately fidgety, interrupts people during meetings,
has been offensive toward coworkers, and has been known to party
excessively on weeknights. Peter asserts that he is just fine; he has
a lot of projects on his mind and is simply standing up for himself
when speaking with others. He likes to go out in the evenings to
unwind. Recognizing probable attention deficit hyperactivity disorder
(ADHD), you interview both the patient and his work buddy,
who is a longtime friend. How would you start your questions?
A. Compared to his parents, how often does the patient …
B. Compared to other people his age, how often does the patient …
C. Compared to his childhood, how often does the patient …
D. Compared to his children, how often does the patient …
The symptoms of ADHD can present differently in patients at different
ages. While hyperactivity is a main symptom in children for example,
this will frequently translate into internal restlessness in adults.
A and D – Incorrect. While ADHD has a strong genetic component, it
is not advised to ask him first to compare himself to either
his children or his parents. An accurate family history would
be beneficial, however.
B – Correct. When trying to diagnose this adult patient with ADHD, it
is preferable to first ask him to compare his behavior to that of
other adults his age, as this will give a better idea of the severity
of his symptoms at this time.
C – Incorrect. While it is important to obtain a medical history, the
patient might not have the best recollection and might not be the
best judge of his behaviors as a child.
According to DSM-5 criteria, what is the maximum age threshold
for symptom onset when making a diagnosis of ADHD?
A. 5
B. 7
C. 12
D. 15
C – Correct. In the fifth edition of the Diagnostic and Statistical Manual
of Mental Disorders, the maximum age threshold for symptom
onset for diagnosing ADHD changed from 7 to 12. Other revisions
included the fact that, although symptoms must have been
present prior to age 12, there does not have to have been impairment
prior to age 12 when diagnosing someone who is older. The
symptom count threshold also changed for adults (defined as age
17 and older), with five (instead of six) symptoms required in the
inattention and/or hyperactive/impulsive categories.
QUESTION THREE
A 15-year-old with inattentive-type ADHD has a hard time staying
focused on the task at hand, has trouble organizing her work, and
relies heavily on her mother to follow through with her homework.
Problem solving is one of the hardest tasks for her. Her
difficulty
with sustained attention could be related to aberrant activation
in the:
A. Dorsolateral prefrontal cortex
B. Prefrontal motor cortex
C. Orbital frontal cortex
D. Supplementary motor cortex
A – Correct. Sustained attention is hypothetically modulated by the
cortico-striatal-thalamic-cortical loop involving the dorsolateral
prefrontal cortex (DLPFC). Inefficient activation of the DLPFC can lead to problems following through or finishing tasks, disorganization,
and trouble sustaining mental effort; the patient exhibits
all these symptoms. The dorsal anterior cingulate cortex is
important in regulating selective attention, and is associated with
behaviors such as losing things, being distracted, and making careless
mistakes. This area is certainly also inefficient in this patient.
B – Incorrect. The prefrontal motor cortex hypothetically modulates
behaviors such as fidgeting, leaving one’s seat, running/climbing,
having trouble being quiet.
C – Incorrect. The orbital frontal cortex regulates impulsivity, which
includes symptoms such as talking excessively, blurting things out,
and interrupting others.
D – Incorrect. Finally, the supplementary motor area is implicated
in planning motor actions; thus, this brain area would be more
involved in hyperactive symptoms
QUESTION FOUR
Which of the following is true regarding cortical brain development
in children with ADHD compared to healthy controls?
A. The pattern (i.e., order) of cortical maturation is different
B. The timing of cortical maturation is different
C. The pattern and timing of cortical maturation are different
D. Neither the pattern nor the timing of cortical maturation is
different
ADHD is a neurodevelopmental disorder characterized by inattentive,
hyperactive, and/or impulsive symptoms. Neuroimaging has been
used to evaluate cortical maturation in children with ADHD compared
to typically developing controls, specifically by comparing the
age of attaining peak cortical thickness in children with and without
ADHD.
A – Incorrect. Research shows that the pattern of cortical maturation
is similar for children with and without ADHD. Specifically, the
primary sensory and motor areas attain peak cortical thickness
earlier in development than do high-order association areas such
as the dorsolateral prefrontal cortex.
B – Correct. There are differences in the timing of cortical maturation
between children with and without ADHD that are apparent as
early as age 7. That is, cortical maturation in children with ADHD
seems to lag behind that of healthy children. In fact, the median
age by which 50% of the cortical points achieve peak thickness is
delayed by 3 years in children with ADHD. Delay is most prominent
in the superior and dorsolateral prefrontal regions, which
are particularly important for control of attention and planning.
Delay is also seen in subcortical structures. A large cross-sectional
mega-analysis demonstrated that the delay in brain maturation is
not attributable to medication use.
Interestingly, there is one brain region in which children with
ADHD achieve peak cortical thickness earlier than typically developing
controls: the primary motor cortex.
C and D – Incorrect.
QUESTION FIVE
Irina is a 35-year-old patient with untreated ADHD who reports
abusing alcohol to manage severe anxiety. Irina’s symptoms may
represent a case where the firing of __________ and __________
neurons innervating her prefrontal cortex is dysregulated and causing
excessive arousal.
A. Norepinephrine; glutamate
B. Norepinephrine; dopamine
C. Dopamine; glutamate
D. Dopamine; serotonin
A – Incorrect.
B – Correct. When norepinephrine (NE) and dopamine (DA) neurotransmission
in the prefrontal cortex are optimally tuned, modest
stimulation of postsynaptic alpha 2A receptors and dopamine 1
receptors allows for efficient cognitive functioning. If NE or DA
neurotransmission is excessive, as in situations of stress or comorbid
conditions such as anxiety or substance abuse, this can lead
to overstimulation of postsynaptic receptors and consequently to
cognitive dysfunction as well as other symptoms.
C – Incorrect.
D – Incorrect.
QUESTION SIX
Martin is a 19-year-old patient with a history of ADHD since
childhood and is treated with an immediate-release amphetamine
(d, l) tablet once a day upon waking. However, Martin has now
started college and his class schedule is spread out throughout the
day. He complains that he is unable to concentrate and takes scattered
notes during his early evening courses. What dose adjustment
would you recommend?
A. Decrease the dose of his immediate-release amphetamine
B. Increase the dose of his immediate-release amphetamine
C. Switch to an extended-release formulation of amphetamine
D. Do not change anything
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A – Incorrect. Immediate-release preparations have a duration of
4–6 hours. Decreasing the dose of immediate-release amphetamine
(d, l) will have no therapeutic effect on helping the patient
manage his symptoms later in the day.
B – Incorrect. Immediate-release preparations have a duration of
4–6 hours. Pharmacological actions of high-dose amphetamine are
not linked to therapeutic action in ADHD, but to reinforcement,
reward, and euphoria in amphetamine abuse. Increasing the dose
of immediate-release formulations elicits pulsatile drug administration
that causes immediate release of DA and could potentially
lead to the highly reinforcing pleasurable effects of drug abuse,
especially at high enough doses and rapid enough administration.
For this reason, using immediate-release stimulants, especially in
young adults, is increasingly being avoided.
C – Correct. Extended-release preparations have a duration ranging
from 8 to 16 hours, depending on the formulation. Controlled-release
(or extended-release) preparations for stimulants result in
slowly rising, constant, steady-state levels of the drug. Under those
circumstances, the firing pattern of DA will theoretically be mostly
tonic, regular, and not at the mercy of fluctuating levels of DA.
Some pulsatile firing is fine, especially when involved in reinforcing
learning and salience.
D – Incorrect. Not changing anything will have no therapeutic effect
on helping the patient manage his symptoms later in the day.
QUESTION SEVEN
Alexandra, a 27-year-old bartender, was diagnosed with ADHD
at age 10. She has been on and off medication since then, first on
immediate-release methylphenidate, then on the methylphenidate
patch. She experimented with illicit drugs during her late adolescence
and is still a heavy drinker. After a few years of self-medication
with alcohol and cigarettes, she is seeking medical attention
again. You decide to put her on 80 mg/day of atomoxetine, one of
the nonstimulant medications effective in ADHD. Why does atomoxetine
lack abuse potential?
A. It decreases norepinephrine levels in the nucleus accumbens,
but not in the prefrontal cortex
B. It increases dopamine levels in the prefrontal cortex but not in
the nucleus accumbens
C. It modulates serotonin levels in the raphe nucleus
D. It increases dopamine in the striatum and anterior cingulate
cortex
Atomoxetine is a selective norepinephrine reuptake inhibitor (NET
inhibitor).
A – Incorrect. In the nucleus accumbens there are only a few NE
neurons and NE transporters. Inhibiting NET in the nucleus
accumbens will not lead to an increase in NE or DA.
B – Correct. The prefrontal cortex lacks high concentrations of dopamine
transporter (DAT), so in this brain region, DA gets inactivated
by NET. Therefore, inhibiting NET in the prefrontal
cortex increases both DA and NE. As only a few NET exist in
the nucleus accumbens, atomoxetine does not induce an increase
in DA and NE in the nucleus accumbens, the reward center of the
brain, thus atomoxetine does not have abuse potential.
C – Incorrect. Atomoxetine does not modulate serotonin levels.
D – Incorrect. The striatum and the anterior cingulate cortex are not
brain areas involved in reward.
QUESTION EIGHT
A 14-year-old patient with ADHD has a rare mutation in the gene
for the dopamine transporter (DAT). In deciding which treatment
to initiate for this patient’s ADHD, you know it will be important
to avoid treatments that depend on normally functioning DAT.
Which of the following drugs are transported into neurons via the
DAT?
A. Methylphenidate
B. Atomoxetine
C. Amphetamine
A – Incorrect. Methylphenidate binds to the DAT and to the norepinephrine
transporter (NET), in both cases acting as an allosteric
modulator. That is, it binds to each transporter at a different site
than the neurotransmitter itself binds. When it does so, it stops the
action of the transporters, preventing reuptake and thus allowing
DA and NE to accumulate in the synapse. Methylphenidate itself
is not taken up into the presynaptic neuron.
B – Incorrect. Atomoxetine is an inhibitor of the NET, and like
methylphenidate it binds at a site distinct from where monoamines
bind. It does not have actions at the DAT.
C – Correct. Like methylphenidate, amphetamine blocks the transporters
for both DA and NE. However, unlike methylphenidate,
which acts as an allosteric modulator, amphetamine is a pseudosubstrate
and a competitive inhibitor at these receptors. That is, it
binds to the same site as the substrate – either DA or NE – thus
competing with the neurotransmitters and preventing them from
being taken up into the terminal. In addition, because amphetamine
is a pseudosubstrate, it is actually transported into the presynaptic
nerve terminal. This is important, because amphetamine
is also a pseudosubstrate and competitive inhibitor at the vesicular
monoamine transporter (VMAT). VMAT is a proton pump that
exchanges DA for protons, packaging the DA into synaptic vesicles
where it is stored for subsequent reuse. When amphetamine binds
to VMAT, it not only blocks the further transport of DA into synaptic
vesicles but is actually packaged into vesicles itself, where
it has the ability to displace stored DA – or NE – back into the
cytoplasm. This occurs only at high doses of amphetamine, as in
cases of amphetamine abuse
QUESTION NINE
A patient with ADHD has not yet had successful treatment: he has
experienced either loss of efficacy toward the end of the day or
efficacy but insomnia at night. He is frustrated and wants to know
what other treatment options exist. The most recently available
new treatments for ADHD represent:
A. Novel neurotransmitter targets
B. New formulations of existing active ingredients
A – Incorrect. Investigational and recently available medications for
ADHD largely still target the DA and/or NE system.
B – Correct. The majority of approved treatments for ADHD, and
specifically new agents approved recently, are formulation variations
of either amphetamine or methylphenidate. Their differences
lie not in the active ingredient but rather in how that active
ingredient is delivered (i.e., release mechanism). Modified-release
formulations
are designed to release the drug in a controlled and
predictable manner that allows for a particular efficacy and safety
profile. Modifying the release of the drug can improve tolerability
by eliminating peaks and troughs in plasma concentration and can
improve efficacy by increasing duration of action as well as by
eliminating peaks and troughs.
QUESTION TEN
Rita is a 28-year-old patient with untreated ADHD. You are currently
deciding between guanfacine and clonidine as potential
treatments for this patient. The selective alpha 2A agonist guanfacine
appears to be:
A. Less tolerated than the alpha 2 agonist clonidine
B. Better tolerated than the alpha 2 agonist clonidine
C. Less efficacious than the alpha 2 agonist clonidine
D. More efficacious than the alpha 2 agonist clonidine
There are two direct-acting agonists for alpha 2 receptors used to treat
ADHD, guanfacine and clonidine. Guanfacine is relatively more selective
for alpha 2A receptors than for other subtypes, whereas clonidine
binds to alpha 2A, alpha 2B, and alpha 2C receptors. Clonidine also has
actions on imidazoline receptors, which is thought to be responsible
for some of clonidine’s sedating and hypotensive actions.
A – Incorrect. Although the actions of clonidine at alpha 2A receptors
exhibit therapeutic potential for ADHD, its actions at other receptors
may increase side effects. By contrast, guanfacine is 15–60
times more selective for alpha 2A receptors than for alpha 2B and
alpha 2C receptors. Additionally, guanfacine is ten times weaker
than clonidine at inducing sedation and lowering blood pressure.
Thus, guanfacine is better tolerated than clonidine.
B – Correct. Guanfacine is better tolerated than clonidine.
C – Incorrect. Guanfacine is 25 times more potent in enhancing prefrontal
cortical function. Thus, it can be said that guanfacine exhibits
therapeutic efficacy with a reduced side effect profile compared
to clonidine.
D – Incorrect. There are no head-to-head comparisons to establish that
guanfacine has superior efficacy to clonidine in ADHD.
QUESTION ELEVEN
Aggregate data suggest that, compared to stimulants, nonstimulants
have:
A. Smaller effect sizes
B. Approximately the same effect sizes
C. Larger effect sizes
A – Correct. Multiple meta-analyses assessing the effects of stimulant
medications have shown that, as a class, nonstimulants have smaller
effect sizes than stimulants. Due to differences in study design,
these meta-analyses do not address potential differences in efficacy
among specific medications.
B and C – Incorrect
QUESTION TWELVE
Isaac is an 8-year-old patient with ADHD. Among male children
with ADHD, which of the following is the most commonly seen
comorbidity?
A. Anxiety
B. Oppositional defiant disorder
C. Depression
A and C – Incorrect. While anxiety and depression are common
comorbidities in patients with ADHD, they are more often
found in girls compared to boys.
B – Correct. Argumentative, disobedient, and aggressive behaviors are
often seen in patients suffering from ADHD and oppositional
symptoms. The presence of comorbid disruptive behavior disorders
such as oppositional defiant disorder, or conduct disorder,
within children with ADHD has been well established. About five
in ten children with ADHD have a behavior or conduct problem
and this is seen at a higher rate in boys than in girls in studies.
QUESTION THIRTEEN
A 44-year-old man was diagnosed with ADHD, inattentive subtype,
in college but has not taken medication for the last several
years. He is seeking treatment now because of declining work performance
following a promotion 7 months ago. Specifically, he
complains of difficulty finishing papers and staying focused during
meetings, and fears that his boss is losing confidence in him. Assessment
confirms a diagnosis of ADHD, inattentive subtype. After 2
months of treatment on a therapeutic dose of a long-acting stimulant,
he states that his focus, sustained attention, and distractibility
are much better, but that he still can’t get organized and that it takes
him longer to complete tasks than it should. At this point, would it
be appropriate to raise the dose of the stimulant to try to address
his residual symptoms?
A. Yes
B. No
A – Incorrect. Dose response studies of stimulant medications suggest
that the optimal dose varies across individuals and depends
somewhat on the domain of function. Specifically, higher doses
may lead to greater improvement of some domains (e.g., vigilance,
attention) but not executive function (e.g., planning, cognitive
flexibility, inhibitory control).
B – Correct. If medication dose is high enough to substantially diminish
symptoms of inattention and distractibility, then executive
function needs to be addressed independently and will not likely
respond to higher medication dosing.
QUESTION FOURTEEN
The cumulative data on the effects of physical exercise as an
adjunctive treatment for children with ADHD have demonstrated
the potential beneficial effects of:
A. Acute aerobic exercise
B. Chronic aerobic exercise
C. A and B
D. Neither A nor B
A and B – Partially correct.
C – Correct. Comparisons have been made between aerobic/nonaerobic,
and acute vs. chronic exercise on cognitive and behavioral symptoms
in children with ADHD. Numerous published studies on exercise
and cognition in children with ADHD have shown that aerobic
exercise appears to be the most effective for improvements in executive
function. Both acute and chronic exercise have beneficial effects
on behavioral and cognitive measures in children with ADHD, when
assessed immediately after exercise. Cognitive measures include
improved response inhibition, cognitive control, attention allocation,
cognitive flexibility, processing speed, and vigilance.
Physical exercise is beneficial as adjunctive treatment, but there is
not enough evidence to suggest that it is a stand-alone treatment.
Exercise may be particularly effective for youth, potentially preventing
or altering the course of ADHD. The literature is promising;
however, the most challenging complications for these types of
studies are random assignment, blinded raters, and adequate control
groups.
D – Incorrect
QUESTION FIFTEEN
A patient with a history of alcohol use disorder has been sober for
6 weeks. He begins medication treatment for adult ADHD and
experiences improvement, but 4 months later relapses with his
alcohol use disorder, engaging in three binge drinking episodes
over a 2-week period. Does this patient need to discontinue medication
treatment for ADHD?
A. Yes, he should be switched to a non-medication treatment
B. Only if he is currently on a long-acting stimulant; nonstimulant
medication is acceptable in this scenario
C. No, both long-acting stimulants and nonstimulant medications
are acceptable in this scenario
A – Incorrect. Because ongoing substance abuse can hinder the treatment
progress of other disorders, in many cases it may be necessary
to address this problem first. However, these are general guidelines
in the ordering of treatment, and one should be careful that this
prioritization of symptoms/conditions does not lead to the neglect
of ADHD treatment in adults. In fact, there is an evidence
base for prescribing ADHD medication for patients in early sobriety
from an alcohol use disorder. Specifically, atomoxetine, which
is approved for adult ADHD, has been shown to be effective for
ADHD and to decrease both alcohol cravings and heavy drinking
days. Atomoxetine is not contraindicated in patients with acute
alcohol use disorder or in patients with liver impairment, so the
patient’s alcohol use would not require medication discontinuation.
It is an appropriate treatment choice; however, it is not the
only appropriate treatment choice.
B – Incorrect. Long-acting stimulant medications are not contraindicated
in patients with acute alcohol use disorder, although they do
carry a black box warning indicating caution in patients with a
history of substance dependence. In general, nonstimulant options
may be preferable to stimulants in patients with substance use disorders,
but long-acting stimulants should remain as a second-tier
option.
C – Correct. Nonstimulant and long-acting stimulant medications are
both options for ADHD co-occurring with substance use disorders;
however, nonstimulants may be preferred as the first-line
approach. If a stimulant is prescribed to a patient in early sobriety
from substance use and/or continued low-level substance use, then
he/she should be monitored closely for misuse of the prescribed
medication.
