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Major Depressive Disorder
The next slide shows the sources for
this series of questions and answers.
As of 1 February 2014.
MDD - sources
Unless otherwise noted, the questions are
• DSM-IV-TR, pages 369-376
• Practice Guideline for the Treatment of
Patients with Major Depressive Disorder,
second edition, published as supplement
to AJP, April 2000
• Guideline Watch on above Disorder,
available at, 2005.
• Since the Boards will be based on DSMIV-TR through 2014 [and maybe beyond],
these screens use DSM-IV-TR, NOT YET
Dx criteria for MDD
Q. List the dx criteria for Major Depressive
Disorder. Assume rule outs of other
disorders, such as never had a manic
episode, and just list the signs/symptoms
of “depressive event.”
MDD criteria
Five or more of nine:
1. *Depressed mood [irritable mood is also an
option in children and adolescence]
2. *Markedly diminished interest in activities.
3. Weight loss of gain of 5%/month.
4. Insomnia or hypersomnia
*Has to have one of these two.
[see next screen for other five]
MDD criteria
5. Psychomotor agitation or retardation
6. Anergy
7. Feelings of worthlessness or guilt
8. Decreased ability to think or to decide
9. Ideation of death or suicide.
Except for #3 above, “every day” applies to
each of these signs
MDD criteria
5. Psychomotor agitation or retardation
6. Anergy
7. Feelings of worthlessness or guilt
8. Decreased ability to think or to decide
9. Ideation of death or suicide.
Except for #3 above, “every day” applies to
each of these signs
Melancholic specifier
Q. What is the criteria for the melancholic
Melancholic specifier
Ans. Meets both A and B infra.
A. Either or both:
1. loss of pleasure in virtually all activities
2. Feels dysphoric even when something
good happens
B. See next screen
Melancholic specifier
B. At least three:
1. Dysphoric feeling is more profound than what
the pt experienced in the past as grief.
2. Dysphoria worse in AM
3. Awakes early in AM
4. Psychomotor retardation or agitation
5. Significant weight loss
6. Inappropriate guilt
Atypical specifier
Q. Basic criteria of atypical specifier is?
Atypical Specifier
1. Reacts positively to good news/events.
2. Two or more of:
-- increase appetite or weight gain
-- hypersomnia
-- heavy/leaden feeling in arms/legs
-- very prone to disabling interpersonal
rejection sensitivity
Melancholic studies
Q. What lab studies are more common in pts
with melancholic specifier than other MDD
Melancholic studies
Ans. More likely to have:
1. Nonsuppression of dexamethasone
2. Plasma, urine and saliva elevated
cortisol levels
3. Abnormal tyramine challenge test
4. Abnormal asymmetry on dichotic
listening tests.
Neurotransmitters monoamine
Q. Name the three major monoamine
systems that are disturbed in MDD.
Neurotransmitters - monoamine
-- serotonin
-- norepinephrine
-- dopamine
[Kandel ER et al: Principles of Neural
Science. 1991]
Neurotransmitters – nonmonoamine
Q. Two non-monoamine neurotransmitters
system that are often disturbed are?
Neurotransmitters – nonmonoamine
-- Corticotropin-releasing factor [CRF]
-- Substance P
[Schecter LE et al: NeuroRx 2005;590-611.]
Q. In depression, 5-hydroxytryptamine
[serotonin] levels are?
Low in CSF, blood platelets and
postmortem brain tissue.
[Cheetham SC et al: Brain Res
MDD - suicide
• Q. Rate of suicide in people with MDD?
MDD - suicide
Ans. Up to 15%.
Suicide prediction
Q. The ability of clinicians to predict suicide
Suicide prediction
Ans. “Poor.” It remains a clinical judgment.
No rating scales are useful to facilitate
clinical judgment, and no “scores” should
be relied upon to be predictive.
MDD – death rate, >55 y/o
Q. What is death rate of people with MDD
and > 55 y/o in comparison to those
without MDD?
MDD – death rate, > 55 y/o
• Ans. Fourfold increase in death rate.
Dysthymia >> MDD
Q. What percentage of people with
dysthymia, who have not yet had MDD,
will go on to have MDD within one year of
onset of dysthymia if not treated?
Dysthymia >> MDD
Ans. 10%
[Text not clear if this is also true of those
Q. About what percent of the population will
have symptoms of MDD over a year from
Ans. 7%
[Kessler RC et al: Arch Gen Psychiatry
MDD – prevalence – gender
Q. Life-time prevalence by gender?
Community sample prevalence by
MDD – prevalence - gender
women: 10-25%
men: 5-12%
Community sample at a given time:
women: 5-9%
men: 2-3%
{So, depending on how the question is asked, at
least 2/3 are women.}
MDD – prevalence - ethnicity
Q. How does ethnicity relate to prevalence?
MDD – prevalence - ethnicity
Ans. DSM says “unrelated.”
MDD – prevalence - education
Q. How does education relate to MDD?
MDD – prevalence - education
Ans. DSM says “unrelated.”
MDD – prevalence - income
Q. Prevalence of MDD and income?
MDD – prevalence - income
Ans. Unrelated.
MDD – prevalence – marital status
Q. Marital status’s relationship to MDD?
MDD – prevalence – marital status
Ans. DSM says unrelated.
MDD – prevalence - generation
Q. Prevalence of MDD and more recent
generations, e.g., born in 1930 in
comparison to born in 1940.
MDD – prevalence - generation
Ans. More recent generations have a higher
rate of MDD. Thus, people in their 60ies
born in the 1940s will have a higher rate
that people who were in their sixties who
were born in the 1930s. Bottom line, the
rate in the population is increasing.
Prevalence - atypical
Q. Among MDD pts, roughly what proportion
have the atypical specifier?
Prevalence - atypical
Ans. About 1/5.
[Quitkin F: J Clin Psychiatry 2002;4:94-99.]
MDD - onset
Q. Most common age of onset?
MDD - onset
Ans. Mid-20s.
MDD – second episode
Q. You are seeing a pt who is having her
first episode of MDD. What are chances
of a second?
MDD - second
A. 60%
MDD - third
Q. You are seeing a pt who is having his
second episode of MDD. What are the
chances of a 3rd?
MDD – third episode
Ans. 70%
MDD – 4th episode
Q. You are treating a pt in her third episode
of MDD. What are her chances of having
a 4th?
MDD – 4th episode
Ans. 90%
MDD >> Bipolar
Q. You are seeing a pt in her first episode of
MDD. What are her chances of later
having dx of bipolar, i.e., chances of
having a manic episode?
MDD >> Bipolar
Ans. DSM’s answer is 5-10%.
{If the examiner’s question focuses on
gender, keep in mind that women are
more likely than men to have their first
bipolar episode be depression whereas
men are more likely to have a manic
episode first. So, in theory, men should be
dxed bipolar sooner than women.}
Suggest future bipolar
Q. What would increase your suspicion that
your pt with MDD is going to go on to have
bipolar disorder?
Suggest future bipolar
- psychotic signs
- psychomotor retardation
- family hx of bipolar disorder
MDD – at one year
Q. Naturalistic studies, i.e., people not
receiving treatment, of MDD people finds
what percentage still meet DSM criteria for
MDD at one year, only have some signs
[“partial”] and have no signs?
MDD – at one year
Still meet criteria: 40%
Partial: 20%
None: 40%
Role of stressors
Q. Stressors, e.g., death of family member,
are more likely to precipitate early
episodes of MDD, later episodes or all
episodes equally?
Role of stressors
Ans. More likely to precipitate the first or
second. Later episodes are less likely to
have a precipitant.
Familial pattern
Q. Name three disorders common in first
degree relatives of pts with MDD.
Family pattern
an Anxiety disorder
Q. Hospitalization is indicated in MDD pts
when? List four.
1. Danger to self or others.
2. Severely disabled and lacks any social
3. Has another medical condition
[including psychiatric] that in combination
with MDD requires hospitalization.
4. Has failed to respond to outpt or partial
Medications - general
Q. Breaking down the medication choices
depending on whether your pt’s MDD is:
severe, or
severe with psychotic signs.
State place of meds with each of the four.
Medications - general
mild: antidepressants meds if preferred by pt [as
opposed to pt preferring psychotherapy]
moderate: antidepressants meds are preferred
[unless ECT is planned]
severe: antidepressant meds are preferred
[unless ECT is planned]
severe with psychotic signs: antidepressants
AND antipsychotics [unless ECT is planned]
as to Citalopram - 1
As of March, 2012, FDA recommends as to
FDA as to citalopram - 2
• Recommending electrolyte and/or
electrocardiographic monitoring in
patients at risk for arrhythmia if
citalopram therapy is considered
• A maximum daily dosage of 20 mg for
all patients older than 60
• Discontinuing the drug if QTc
measurements are consistently greater
than 500 ms
FDA as to citalopram - 3
• The label will continue to state that
citalopram should be "avoided, if
possible," in patients with or at risk for
prolonged QT interval, including those
prone to low blood levels of potassium
and magnesium. Also, per the FDA's
order of last August, the maximum
dose in patients 60 and younger should
be 40 mg/day.
FDA as to citalopram - 4
• QT interval prolongation can result in
the fatal arrhythmia known as torsade
de pointes.
• Patients with low potassium or
magnesium levels should receive
supplements to normalize them before
starting on citalopram, the agency said.
FDA as to citalopram - 5
Max dose for those > 60 y/o: 20 mg/d
Discontinue if QTc measurements are > 500
FDA as to citalopram - 6
• If the pt has congenital long QT
syndrome, citalopram is not
recommended in these patients but it is
recognized that there may be some
patients with this condition who could
benefit from a low dose of citalopram
and who lack viable alternatives.
Q. List 7 factors that would lead one to tilt
toward providing psychotherapy for your pt
with MDD.
1] MDD is mild or moderate level of severity
2] Pt preference
3] Pregnant, lactating or wish to become pregnant
4] Co-morbid personality disorder
5] Presence of substantial stressors
6] Substantial interpersonal difficulties
7] Substantial intrapsychic conflict
Psychotherapy - evidence
Q. Two psychotherapies with the most
“research-documented efficacy” in MDD?
Psychotherapy - evidence
-- CBT
-- Interpersonal therapy
Psychotherapy - reappraisal
Q. After how many weeks of psychotherapy
should one reappraise if the
psychotherapy is the correct choice?
Psychotherapy - reappraisal
Ans. 4 – 8 weeks.
Combination therapy
Q. When to use both meds and
Ans. Same 7 as to psychotherapy with the
following 3 addictions:
-- Can also consider with severe level of
the disorder, not just mild or moderate.
-- Poor response to just meds or just
-- Poor compliance with just meds or just
Combination - reappraisal
Q. Pt has not shown even moderate
improvement after combination of SSRIs
and CBT after 8 weeks. Next you switch to
venlafaxine, gradually go to max dose and
continues CBT, and still no improvement
after another 8 weeks. What to do?
Combination - reappraisal
Consider a consultation or ECT.
Q. List 6 reasons you would consider ECT
as treatment of choice.
ECT - 1
1] Pt’s preference
2] Prior good results with ECT
3] Pt has medical conditions that preclude
use meds and conditions too severe for
psychotherapy. Medical conditions would
include pregnancy.
4] see next slide
ECT - 2
4] Catatonic
5] Urgent need for response, e.g. very
suicidal or not eating.
6] Very high level of severity of the MDD
Initial choice of a med
Q. Practice guideline list one whole class,
two tricyclics, one dopaminenorepinephrine reuptake inhibitor, two
serotonin-norepinephrine reuptake
inhibitor, and one norepinephrineserotonin modulator as “likely to be
effective for most patients” as an initial
med choice for MDD. Name the class,
then name the two tricyclics, then the
other three meds.
Initial choice of med
Class: SSRIs
Tricyclics: desipramine and nortriptyline
Dopamine-norepinephrine reuptake inhibitor:
Serotonin-norepinephrine reuptake inhibitor:
venlafaxine or duloxetine
Norepinephrine-serotonin modulator: mirtazapine
Q. Concern about nefazodone?
Ans. Life-threatening hepatic failure.
Partial response
Q. Your pt has partially responded to an
SSRI in 6 weeks, dose pushed to max,
and still not improved further at 12 weeks,
what to do?
Partial response
Ans. Augment with:
-- a non-MAOI antidepressant
-- Li
-- thyroid hormone
-- anticonvulsant mood stabilizer
-- psychostimulant
Also acceptable: add or increase frequency
of psychotherapy
No response
Q. If pt placed on SSRI and no response at
max dose levels after 12 weeks, what to
No response
Change to another antidepressant or try
TCAs - problems
Q. Tricyclics are especially problematic in
pts with what two medical conditions [not
including suicidal]?
-- cardiovascular conditions
-- acute-angle glaucoma
Duloxetine - problems
Q. Duloxetine is usually avoid when the pt
has what two illnesses?
Duloxetine - problems
-- chronic hepatitis
-- alcoholism
Serotonin rebound
Q. Your pt suddenly discontinues an SSRI.
What are some symptoms of such?
Serotonin rebound
-- flu-like symptoms
-- paresthesias
-- lightheadedness
-- anxiety
MAOIs - action
Q. What is the action of MAOIs?
For how long?
MAOIs - action
Ans. Form bond with MAO enzyme that in
turn decreases the degradation of norepinephrine and serotonin, thus increasing
synaptic concentration of those two
amines. Two weeks.
[Bodkin JA: Curr Psychiatry 2006;5:79-83]
MAOIs – used
Q. Name the three MAOIs used in
MAOIs - used
-- phenelzine
-- selegiline transdermal system
-- tranylcypromine
-- isocarboxazid is rarely used today
MAOIs & fluoxetine
Q. Pt is on fluoxetine, what is wash out
period before one can begin an MAOI?
MAOI & fluoxetine
Ans. 5 weeks.
Fluoxetine & MAOI
Q. Pt is on phenelzine and is to be switched
to fluoxetine. How long a wash out?
Fluoxetine & MAOI
Ans. 2 weeks
MAOI & venlafaxine
Q. Pt is on venlafaxine and is to be switched
to tranylcypromine. How long a wash out?
MAOI & venlafaxine
Ans. 2 weeks.
[This “2 weeks” answer will work for most of
the other antidepressants.]
Atypical - bupropion
Q. Bupropion useful in atypical subtype of
Atypical - bupropion
Ans. Yes, works as well as SSRIs.
[I’m unaware of any studies of bupropion v.
[Thase ME et al: J Clin Psychiatry
Atypical - CBT
Q. Can CBT do as well with atypical MDD as
an MAOI?
Atypical - CBT
Ans. Yes. CBT did as well as phenelzine in
a ten week study.
[Remember in the exam, never bet against
[Jarrett RB et al: Arch Gen Psychiatry
Treatment failure
Q. Always a correct answer in the face of
treatment failure?
Treatment failure
Ans. 1]Non-compliance with treatment?
2]Reconsider dx.
a] General medical condition?
b] Substance-related disorder?
Continuation phase
Q. Pt did not respond to escitalopram, 20
mg/d, and was switched to venlafaxine ER
at the 7th week and gradually increased to
225 mg/d of venlafaxine ER and
symptoms remitted at the 13th week. What
now as to medicating?
Continuation phase
Ans. 16 to 20 weeks of the same med at
same doses that achieved remission.
Discontinuation of medications
Q. If pt has done well for 12 months while on
an antidepressant, if med is to be
discontinued, what to do?
Discontinuance of meds
1. Establish a plan to restart med in case
of relapse.
2. Taper slowly over at least several