Trastorno Bipolar Flashcards
QUESTION ONE
A 25-year-old woman has recently been diagnosed with bipolar
disorder, 6 years after her symptoms began. She has had no mood
stabilizing treatment in that time. According to the kindling model
and allostatic load hypothesis, what progressive pattern of illness
would you expect this patient to have exhibited over the course of
the last 6 years?
A. Shorter interval between episodes, worsened emotionality, worsened
cognitive impairment
B. Longer interval between episodes, worsened emotionality, worsened
cognitive impairment
C. Shorter interval between episodes, worsened emotionality, minimal
change in cognitive impairment
D. Longer interval between episodes, worsened emotionality, minimal
change in cognitive impairment
A – Correct. Throughout the course of illness, patients with bipolar
disorder will experience manic or hypomanic episodes, depressive
episodes, and inter-episode periods during which they are generally
well but may have subsyndromal symptoms. The pattern of
episodes can differ for each patient; however, in general the clinical
course of bipolar disorder is progressive. That is, as the number of
episodes a person has had increases, the interval between episodes
gets shorter and emotionality may worsen. In addition,
cognitive impairment seems to worsen with the length of
illness. Increasing episode number is also associated with reduced
likelihood of treatment response.
Models for how these changes may come to be posit that recurrent
mood episodes are associated with repeated physiological insults
that add up and kindle, like a spark bursting into fire. This could
compromise endogenous compensatory mechanisms, leading to
cell apoptosis that in turn causes rewiring of the brain circuits
involved in mood regulation and cognition. This can render one
more vulnerable to the effects of stressors, increasing risk of future
episodes and thus perpetuating the vicious spiral.
B, C, and D – Incorrect.
QUESTION TWO
A 32-year-old woman with bipolar I disorder has just found out
that she is 6 weeks pregnant. Her mania has been stable on a combination
of lithium, valproate, and quetiapine, but she is unsure
about the safety of maintaining her medications during her
pregnancy.
Which, if any, of the patient’s medications has known
teratogenic effects?
A. Lithium
B. Valproate
C. Quetiapine
D. A and B
E. A, B, and C
A – Partially correct. Lithium has evidence of increased risk of major
birth defects and cardiac anomalies, especially Ebstein’s anomaly,
although a recent review suggested that the risk of cardiac anomalies
may be overemphasized. With lithium, the risk of Ebstein’s
anomaly is perhaps 1/2500 (basal risk is 1/20 000). It is typically
detectable in utero by ultrasonography and can often be corrected
surgically after birth. No long-term neurobehavioral effects of
late-term neonatal lithium exposure have been observed. Lithium
is not contraindicated during pregnancy, and the risks must be
weighed against the benefits. If lithium is continued, serum lithium
levels must be monitored every 4 weeks, then every week
beginning at 36 weeks. Lithium administration during delivery
may be associated with hypotonia in the infant, and most recommend
withholding lithium for 24–48 hours before delivery, with
monitoring during and after delivery of both baby and mother.
B – Partially correct. Valproate is associated with increased risk of
neural tube defects (e.g., spina bifida) and other congenital anomalies.
Cases of developmental delay in the absence of teratogenicity
associated with fetal exposure have also been identified. Increased
risk of lower cognitive test scores in children whose mothers took
valproate during pregnancy has also been observed. Generally, it is
recommended to discontinue valproate during pregnancy. If valproate
is continued, clotting parameters should be monitored and
tests to detect birth defects should be performed. Patients should
begin folate 1 mg/day early in pregnancy to reduce risk of neural
tube defects and consider vitamin K during the last 6 weeks of
pregnancy to reduce risks of bleeding.
C – Incorrect. Quetiapine does not have known teratogenic effects, and
cumulative data with atypical antipsychotics do not show a risk of
major malformations. There is a risk of abnormal muscle movements
and withdrawal symptoms in newborns whose motherstook an antipsychotic during the third trimester; symptoms may
include agitation, abnormally increased or decreased muscle tone,
tremor, sleepiness, severe difficulty breathing, and difficulty feeding.
If quetiapine or another atypical antipsychotic is used during
pregnancy, weight gain and the risk for gestational diabetes should
be more carefully monitored, with glucose tolerance testing (as
opposed to glucose challenge testing) at 14–16 weeks and again at
28 weeks. After delivery, infants should be monitored for neonatal
withdrawal, toxicity, extrapyramidal side effects, and sedation.
D – Correct. Lithium and valproate both have known teratogenic
effects.
E – Incorrect
QUESTION THREE
A 25-year-old woman presents with a major depressive episode.
She has a history of hospitalizations and treatment for manic episodes
but is not currently taking any medication. The agents with
the strongest evidence of efficacy in bipolar depression are:
A. Lamotrigine, lithium, quetiapine
B. Quetiapine, olanzapine-fluoxetine, lurasidone
C. Olanzapine-fluoxetine, lurasidone, lamotrigine
D. Lurasidone, lamotrigine, lithium
A – Incorrect. Controlled data assessing the efficacy of lithium in bipolar
depression are limited; in a recent network meta-analysis lithium
was not found to be effective compared to placebo in acute
bipolar depression. However, lithium does have evidence for reducing
suicidality. In the same network meta-analysis, lamotrigine
was effective compared to placebo in terms of response but not
remission.
B – Correct. Quetiapine, olanzapine-fluoxetine, and lurasidone have
all demonstrated consistent efficacy in bipolar depression and are
approved for this stage of the disorder.
Drug Daily dose
Lurasidone 20–120 mg
Olanzapine-fluoxetine 6–12/25–50 mg
Quetiapine 300 mg
C – Incorrect. Consistent evidence of efficacy in bipolar depression
does not exist for lamotrigine.
D – Incorrect. Consistent evidence of efficacy in bipolar depression
does not exist for lamotrigine or lithium.
QUESTION FOUR
Gina is a 24-year-old patient with no psychiatric history. She gave
birth to her first child 2 weeks ago and now presents with symptoms
of depression. She scores a 20 on the Edinburgh Postnatal
Depression Scale (EPDS; possible depression). Which of the following
courses of action should be the next step?
A. Readminister the Edinburgh Postnatal Depression Scale (EPDS)
at 1 month postpartum
B. Initiate treatment with an antidepressant
C. Administer a (hypo)mania screening tool such as the Mood
Disorders Questionnaire (MDQ)
A – Incorrect. Although a follow-up administration of the EPDS may
provide information on disease course, there are several great risks
to untreated postpartum depression.
B – Incorrect. Although monotherapy with an antidepressant may be
appropriate and effective for the treatment of postpartum depression,
it is critical that patients with postpartum depression are
screened for symptoms of (hypo)mania before initiating an antidepressant
monotherapy that may be contraindicated.
C – Correct. Given that many patients with postpartum depression
often exhibit symptoms of bipolarity or mixed features (for whom
antidepressant monotherapy is not recommended), it is crucial that
all patients screened as positive on the EPDS are also screened for
(hypo)mania.
QUESTION FIVE
A 15-year-old girl presents with symptoms of depression. She has
always been a good student and a caring and responsible sister to
her two younger siblings. A few months ago, she suddenly became
withdrawn and felt sad much of the time. She has had adequate
trials of two different antidepressants with little improvement. Her
MADRS score is currently 35, indicating severe depression. She
also endorses feelings of hostility and aggression and has recently
started getting into physical altercations with her peers. There is
no information regarding family history as the patient is adopted.
Although not definitive, this particular symptom profile may be
more suggestive of:
A. Unipolar depression
B. Bipolar depression
A – Incorrect. Data to date suggest that, although in no way definitive,
there may be certain symptoms and course-related factors that help
differentiate between unipolar and bipolar depression. This patient’s
presentation, which includes rapid and early onset of severe depression,
hostility, aggression, and impulsivity, raises the suspicion that
this may be part of a bipolar illness rather than a unipolar illness.
B – Correct. The patient’s presentation includes multiple factors that
may be more likely to occur with bipolar disorder rather than with
unipolar depression. This is not definitive but does suggest caution
when making treatment decisions. Although also not definitive,
family history and input from someone close to the patient are
generally more valuable than specific symptoms.
Suspect bipolar depression if:
Positive family history of bipolar disorder
Early onset of first depressive episode (<25 years)
Greater number of lifetime affective episodes
Postpartum depressive episodes
Rapid onset of depressive episodes
Greater severity of depressive episodes
Worse response to antidepressants
Antidepressant-induced hypomania
Psychotic features
Atypical depressive symptoms (e.g., leaden paralysis)
Impulsivity
Aggression
Hostility
Comorbid substance use disorder
QUESTION SIX
The “bipolar storm” refers to the concept that unstable, unregulated,
and excessive neurotransmission occurs at synapses in specific
brain regions, and both voltage-sensitive sodium channels and
voltage-
sensitive calcium channels are involved in this excessive
stimulation of glutamate release. Which drugs would theoretically
reduce glutamate release by blocking voltage-sensitive sodium
channels?
A. Valproate and lamotrigine
B. Pregabalin and gabapentin
C. Levetiracetam and amantadine
A– Correct. Valproate is a nonspecific voltage-sensitive sodium
channel modulator and lamotrigine also blocks voltage-sensitive
sodium channels, hypothesized to lead to reduction in glutamate
release.
B – Incorrect. Pregabalin and gabapentin are alpha 2 delta ligands at
voltage-sensitive calcium channels, which also leads to reduction
in glutamate release.
C – Incorrect. Levetiracetam is a modulator of the synaptic vesicle
protein SV2A, and amantadine is an antagonist of the N-methyld-
aspartate (NMDA) receptor. While this combination of drugs
would lead to reduced glutamate release, it would not do so via the
mechanisms of action asked
QUESTION SEVEN
A 24-year-old man has been taking lithium for 3 years to treat his
bipolar disorder. What are two primary candidates for the direct
mechanisms of lithium?
A. Inhibition of glycogen synthase kinase 3β (GSK-3β) and inositol
monophosphatase (IMPase)
B. Activation of GSK-3β and IMPase
C. Inhibition of GSK-3β and activation of IMPase
D. Activation of GSK-3β and inhibition of IMPase
A – Correct. Lithium has been a first-line treatment for bipolar disorder
for decades, yet its mechanism of action is still not certain.
There is, however, substantial evidence that lithium exerts neuroprotective
effects that are likely downstream from its primary
mode of action. Two primary candidates for the direct mechanisms
of lithium are the inhibition of GSK-3β and the inhibition of
IMPase. GSK-3β is involved in the regulation of inflammation and
is, in general, pro-apoptotic. Specifically, it inhibits transcription
factors that would otherwise induce production of cytoprotective
proteins such as brain-derived neurotrophic factor (BDNF); thus,
its inhibition may be neuroprotective. IMPase indirectly leads to
an increase in protein kinase C, which is overactive in mania. Thus,
inhibition of IMPase by lithium could potentially reduce manic
symptoms.
B – Incorrect. Lithium is thought to inhibit GSK-3β and IMPase, not
activate them.
C – Incorrect. Lithium is thought to inhibit IMPase, not activate it.
D – Incorrect. Lithium is thought to inhibit GSK-3β, not activate it.
QUESTION EIGHT
Jimmy is a 20-year-old man recently diagnosed with major depressive
disorder with mixed features. Approximately what percentage
of patients with major depressive disorder exhibit subthreshold
symptoms of (hypo)mania during a major depressive episode?
A. 6%
B. 26%
C. 46%
A and C – Incorrect.
B – Correct. Approximately 26% of patients diagnosed with major
depressive disorder endorse symptoms of subthreshold (hypo)mania
during major depressive episodes and meet criteria for the mixed
features specifier.
QUESTION NINE
A 24-year-old man with bipolar disorder is being initiated on lithium,
with monitoring of his levels until a therapeutic serum concentration
is achieved. Once the patient is stabilized, how often
should his serum lithium levels be monitored (excluding one-off
situations such as dose or illness change)?
A. Every 2 to 3 months
B. Every 6 to 12 months
C. Every 1 to 2 years
D. Routine monitoring is not necessary
A – Incorrect. Initially, lithium levels should be monitored every 1 to
2 weeks until the desired serum concentration is achieved, and
then every 2 to 3 months for the first 6 months. However, this frequency
of monitoring is not required once the patient is stabilized.
B – Correct. Once a patient is stabilized, lithium levels need only be
monitored every 6 to 12 months.
C – Incorrect.
D – Incorrect.
QUESTION TEN
A 32-year-old woman with bipolar disorder has been maintained
on 900 mg/day of lithium. She was doing well for a long time and
had even been able to lose the weight she had initially gained with
lithium. She broke up with her boyfriend 5 months ago and has
been feeling depressed ever since. You augment her with 300 mg/
day of quetiapine, but after several weeks she complains of weight
gain and wants to change medications. Blockade of which two
receptors was most likely responsible for this weight gain induced
by quetiapine?
A. Muscarinic 1 and serotonin 6
B. Serotonin 2A and muscarinic 3
C. Serotonin 2C and histamine 1
D. Dopamine 2 and alpha 1
adrenergic
A – Incorrect. Blockade of muscarinic M1 receptors can lead to
constipation, blurred vision, dry mouth, and drowsiness, but not
weight gain. The function of the serotonin 6 receptors has not
been identified yet.
B – Incorrect. Blockade of serotonin 2A receptors is considered a
beneficial property of antipsychotics leading to less extrapyramidal
symptoms. Blockade of muscarinic M3 receptors has been
linked to inducing cardiometabolic risk, but has not been linked to
weight gain per se.
C – Correct. Blockade of serotonin 2C receptors and histamine 1
receptors has been linked to weight gain.
D – Incorrect. Dopamine 2 blockade is the main property of antipsychotics
and, if continuous, this blockade can lead to motor side
effects, but not to weight gain. Alpha 1 blockade can result in
decreased blood pressure, dizziness, and drowsiness, but does not
lead to weight gain.
QUESTION ELEVEN
Maria is a 31-year-old patient with bipolar II disorder. During
major depressive episodes, this patient often experiences several
symptoms of hypomania, including flight of ideas, increased
risk-taking behavior, and increased talkativeness. According to data
from the Stanley Foundation Bipolar Network, how many patients
with bipolar disorder exhibit subsyndromal hypomanic symptoms
during a major depressive episode in at least one single visit?
A. 5%
B. 25%
C. 45%
D. 65%
E. 85%
A, B, C, and E – Incorrect.
D – Correct. According to data published by the Stanley Foundation
Bipolar Network, as many as 65% of patients with bipolar disorder
exhibit symptoms of subsyndromal hypomania during depressive
episodes at a single visit.
QUESTION TWELVE
Thomas, a 28-year-old patient with major depressive disorder with
mixed features, complains of significant irritability and agitation
that are affecting his family and work. Which psychotropic treatment(
s) can be considered as ALTERNATIVE maintenance treatments
to antidepressants?
A. An atypical antipsychotic such as quetiapine
B. A mood stabilizer such as lamotrigine
C. A benzodiazepine such as lorazepam
D. A and B only
E. B and C only
A – Partially correct. Atypical antipsychotics with mood-stabilizing
properties (such as quetiapine) are recommended as first-line treatments
in patients with major depressive disorder with mixed features.
B – Partially correct. Mood stabilizers (such as lamotrigine) are recommended
as first- or second-line treatments in patients with major
depressive disorder with mixed features.
C and E – Incorrect. Although benzodiazepines (such as lorazepam)
may be useful for reducing acute mania, there are no data
supporting the use of benzodiazepines in the maintenance
treatment of major depressive disorder with mixed features.
Additionally, the extended use of benzodiazepines is not
recommended due to high risk for dependence, tolerance,
and withdrawal.
D – Correct. Both atypical antipsychotics with mood-stabilizing properties
and mood stabilizers have shown some efficacy in the treatment
of major depressive episodes with mixed features and are
therefore recommended as first- or second-line treatments.
QUESTION THIRTEEN
A 21-year-old patient with major depressive disorder presents with
several symptoms that may indicate the presence of mixed features.
Which of the following symptoms is included in the DSM-5
mixed features specifier diagnostic criteria?
A. Irritability
B. Increased goal-directed activity
C. Distractibility
D. Agitation
B – Correct. Although increased goal-directed activity is NOT one of
the most common symptoms exhibited by patients experiencing a
major depressive episode with mixed features, it is included in the
DSM-5 mixed features specifier diagnostic criteria.
A, C, and D – Incorrect. Although irritability, distractibility, and psychomotor
agitation are among the most common
symptoms of depression with mixed features, they are
excluded from the DSM-5 mixed features criteria
due to the overlap of these symptoms with other disorders
(e.g., anxiety disorders) and between mania and
depression.
QUESTION FOURTEEN
A patient with bipolar depression has been treated for 6 months
with lamotrigine plus an atypical antipsychotic with partial
response. The decision is made to stop the atypical antipsychotic;
however, during down-titration, the patient develops withdrawal
dyskinesias. No treatment for the dyskinesias is initiated, and after 2
weeks they still remain. Which of the following is true?
A. If the withdrawal dyskinesias still remain after 2 weeks, they are
likely to be permanent
B. The patient’s withdrawal dyskinesias may take several weeks to
months to resolve
A– Incorrect. Withdrawal dyskinesias are often reversible with time
and usually resolve within a few weeks; however, they can take
several months to resolve, depending on their seriousness. Thus,
although the patient’s withdrawal dyskinesias still remain after
2 weeks, this does not indicate that they are likely to be permanent.
B – Correct. It may take several weeks to months for the patient’s
withdrawal dyskinesias to resolve.
QUESTION FIFTEEN
A 38-year-old patient with bipolar disorder has been taking valproate
with only partial control of depressive symptoms, and her
clinician elects to add lamotrigine. Compared to lamotrigine
monotherapy, what adjustment should be made to the lamotrigine
titration schedule in the presence of valproate?
A. Slower titration schedule, half the target dose
B. Slower titration schedule, same target dose
C. Same titration schedule, half the target dose
D. Same titration schedule, same dose
A – Correct. Valproate increases the plasma levels of lamotrigine, so
when adding lamotrigine to valproate, the target dose is lower
and titration is slower (in comparison to initiating lamotrigine
monotherapy):
* For the first 2 weeks: 25 mg every other day
* Week 3: increase to 25 mg/day
* Week 5: increase to 50 mg/day
* Week 6: increase to 100 mg/day
B, C, and D – Incorrect.
