Major Depressive Disorder The next slide shows the sources for this series of questions and answers.

As of 23Aug07. MANY OF THE EARLY SLIDES IN THIS POWERPOINT ON NEUROSCIENCE ARE MORE DIFFICULT THAN ORAL EXAMS

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.

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 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 Continued: 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 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 Continued 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 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?

Ans. 7% Prevalence [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?

Ans. Mid-20s.

MDD - onset

MDD – second episode Q. You are seeing a pt who is having her first episode of MDD. What are chances of a second?

A. 60% MDD - second

MDD - third Q. You are seeing a pt who is having his second episode of MDD. What are the chances of a 3 rd ?

MDD – third episode Ans. 70%

MDD – 4 th episode Q. You are treating a pt in her third episode of MDD. What are her chances of having a 4 th ?

Ans. 90% MDD – 4 th episode

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 supports 3. 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 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]

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 -- 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 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. Reconsider dx. General medical condition? Substance-related disorder?

Continuation phase Q. Pt did not respond to escitalopram, 20 mg/d, and was switched to venlafaxine ER at the 7 th week and gradually increased to 225 mg/d of venlafaxine ER and symptoms remitted at the 13 th 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

dis

continued, 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.