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 from:

• 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 www.psych.org., 2005.

DSM-IV-TR

• Since the Boards will be based on DSM-IV-TR through 2014 [and maybe beyond], these screens use DSM-IV-TR, NOT YET DSM-5.

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

Ans.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

Continued:5. Psychomotor agitation or retardation6. Anergy7. Feelings of worthlessness or guilt8. Decreased ability to think or to decide9. Ideation of death or suicide.Except for #3 above, “every day” applies to

each of these signs

MDD criteria

Continued:5. Psychomotor agitation or retardation6. Anergy7. Feelings of worthlessness or guilt8. Decreased ability to think or to decide9. 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 specifier?

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

ContinuedB. At least three:1. Dysphoric feeling is more profound than what

the pt experienced in the past as grief.2. Dysphoria worse in AM3. Awakes early in AM4. Psychomotor retardation or agitation5. Significant weight loss6. Inappropriate guilt

Atypical specifier

Q. Basic criteria of atypical specifier is?

Atypical Specifier

Ans.

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 pts?

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

Ans.-- serotonin-- norepinephrine-- dopamine

[Kandel ER et al: Principles of Neural Science. 1991]

Neurotransmitters – non-monoamine

Q. Two non-monoamine neurotransmitters system that are often disturbed are?

Neurotransmitters – non-monoamine

Ans.

-- Corticotropin-releasing factor [CRF]

-- Substance P

[Schecter LE et al: NeuroRx 2005;590-611.]

5-HT

Q. In depression, 5-hydroxytryptamine [serotonin] levels are?

5-HT

Ans.

Low in CSF, blood platelets and postmortem brain tissue.

[Cheetham SC et al: Brain Res 1988;443:272-280]

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 is?

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 treated.]

Prevalence

Q. About what percent of the population will have symptoms of MDD over a year from onset?

Prevalence

Ans. 7%

[Kessler RC et al: Arch Gen Psychiatry 2005:62:617-627]

MDD – prevalence – gender

Q. Life-time prevalence by gender?

Community sample prevalence by gender?

MDD – prevalence - gender

Ans. Life-time:

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

Ans.

- 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

Ans.

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

Ans.

MDD

an Anxiety disorder

alcoholism

Hospitalization

Q. Hospitalization is indicated in MDD pts when? List four.

Hospitalization

Ans. 1. Danger to self or others.2. Severely disabled and lacks any social supports3. Has another medical condition [including psychiatric] that in combination with MDD requires hospitalization.4. Has failed to respond to outpt or partial treatment.

Medications - general

Q. Breaking down the medication choices depending on whether your pt’s MDD is:

mild,

moderate,

severe, or

severe with psychotic signs.

State place of meds with each of the four.

Medications - general

Ans.

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]

FDA as to Citalopram - 1

As of March, 2012, FDA recommends as to citalopram?

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 ms.

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.

Psychotherapy

Q. List 7 factors that would lead one to tilt toward providing psychotherapy for your pt with MDD.

Psychotherapy

Ans.

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

Ans.

-- 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 psychotherapy?

Combination

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 psychotherapy

-- Poor compliance with just meds or just psychotherapy

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

Ans.

Consider a consultation or ECT.

ECT

Q. List 6 reasons you would consider ECT as treatment of choice.

ECT - 1

Ans.

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 dopamine-norepinephrine reuptake inhibitor, two serotonin-norepinephrine reuptake inhibitor, and one norepinephrine-serotonin 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

Ans.

Class: SSRIs

Tricyclics: desipramine and nortriptyline

Dopamine-norepinephrine reuptake inhibitor:

bupropion

Serotonin-norepinephrine reuptake inhibitor: venlafaxine or duloxetine

Norepinephrine-serotonin modulator: mirtazapine

nefazodone

Q. Concern about nefazodone?

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-- psychostimulantAlso 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 do?

No response

Ans.

Change to another antidepressant or try psychotherapy.

TCAs - problems

Q. Tricyclics are especially problematic in pts with what two medical conditions [not including suicidal]?

TCAs

Ans.

-- cardiovascular conditions

-- acute-angle glaucoma

Duloxetine - problems

Q. Duloxetine is usually avoid when the pt has what two illnesses?

Duloxetine - problems

Ans.

-- chronic hepatitis

-- alcoholism

Serotonin rebound

Q. Your pt suddenly discontinues an SSRI. What are some symptoms of such?

Serotonin rebound

Ans.

-- 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 nor-epinephrine 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 psychiatry.

MAOIs - used

Ans.

-- 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 MDD?

Atypical - bupropion

Ans. Yes, works as well as SSRIs.

[I’m unaware of any studies of bupropion v. MAOIs.]

[Thase ME et al: J Clin Psychiatry 2005;66:974-981]

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 CBT.]

[Jarrett RB et al: Arch Gen Psychiatry 1999;56:431-437]

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

Ans.

1. Establish a plan to restart med in case of relapse.

2. Taper slowly over at least several weeks.