Financial Disclosures none 1 Update on Mood Disorders Outline - - PDF document

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Update on Mood Disorders October 9, 2015

Descartes Li, M.D. Clinical Professor University of California, San Francisco descartes.li@ucsf.edu

Financial Disclosures

none

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Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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Diagnosis of Depression Key issues 1) Rule out Medical conditions causing psychiatric symptoms 2) Rule out Substance abuse or iatrogenic medications 3) Rule out Bipolar disorder (ie, screen for mania or hypomania) The Three S’s of the Psychiatric Interview

1) S – Stressors/triggers 2) S – Suicidality 3) S – Substance Abuse

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Physical Health Questionnaire-9, depression scale

• Nine (9) items
• Easy to score
• There are two components of the

PHQ-9: – Diagnostic – Severity

• Google: “PHQ-9”

http://www.depression-primarycare.org/clinicians/toolkits/materials/forms/ phq9/

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Dysthymic Disorder Major Depressive Disorder Cyclothymic Disorder Bipolar I Disorder Bipolar II Disorder

Major Depressive Episode —Diagnostic Criteria

• signif wt Δ (↓ or ↑)
• insomnia or hypersomnia
• Ψmotor agitation/retardation

(PMA/PMR)

• fatigue or anergia
• guilt/worthlessness (G/W)
• ↓’d concentration
• recurrent thoughts of death
• r SI
• ↓’d mood
• anhedonia

Sleep Interest Guilt Energy Concentration Appetite Psychomotor Suicide

5 symptoms (with ≥1 sx in blue)

MDE = ≥2wks of

Criterion A. Five or more of the following…

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Major Depressive Episode —Diagnostic Criteria (cont.)

Criterion B. The symptoms cause clinically significant distress or impairment in social,

• ccupational, or other important areas of

functioning. Criterion C. The episode is not attributable to the physiological effects of a substance

• r to another medical condition.

Criteria A-C represent a major depressive episode

Major Depressive Disorder —Diagnostic Criteria (cont.)

*note: deletion of Bereavement exclusion in DSM 5

Criterion D. The occurrence of the MDE is not better explained by schizoaffective disorder, schizophrenia, etc. Criterion E. There has never been a manic episode or a hypomanic episode.

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Major Depressive Episode: SIG E CAPS criteria

Depressed mood (or anhedonia), plus: S –Sleep symptoms I—lack of Interest. G—feelings of Guilt E—lack of Energy. C--lack of Concentration. A--lack of Appetite. P--Psychomotor changes S--thoughts of Suicide

Specifiers

• Atypical
• Catatonia
• Melancholic
• Mixed features
• Postpartum onset
• Psychotic features

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Specifiers

(that are risk factors for bipolar disorder)

• Atypical
• Catatonia
• Melancholic
• Mixed features
• Postpartum onset
• Psychotic features

What is Atypical depression?*

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*not in syllabus

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Clinical scenario*

A 28yo woman has an intense but brief (3 days) romantic relationship with a married man. Two weeks later, she comes to your office and reports severely depressed mood (“I am devastated”), increased carbohydrate intake, and sleeping 12-14 hours per day. Other comments include: “I can’t move I’m so tired.” At baseline, she is highly sensitive to the comments and opinions of others, easily going from euphoria to depression based on brief interactions.

• 1. Which subtype of depression is demonstrated?

a) Atypical, b) Catatonic, c) Melancholic, d) Psychotic, e) Not Otherwise Specified Answer is a)

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*Not in syllabus

Atypical Depression*

DSM 5 Criteria for Major Depressive Episode with Atypical Features:

• A. Mood reactivity (ie, mood brightens in response

to actual or potential positive events)

• B. Two (or more) of the following:
• significant weight gain or increase in appetite
• hypersomnia
• lead paralysis (ie, heavy, leaden feelings in arms or legs)
• long-standing pattern of interpersonal rejection sensitivity

(not limited to episodes of mood disturbance) that results in significant social or occupational impairment

• C. Criteria are not met for With Melancholic

Features or With Catatonic Features during the same episode

*not in syllabus

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Other DSM -5 depressive disorders

• Persistent Depressive Disorder

(dysthymia)

• Premenstrual Dysphoric Mood

Disorder (PMDD)

• Disruptive Mood Dysregulation

Disorder

N.B. DSM with diagnostic hierarchy: Mood>Psychosis>other (anxiety, somatic, personality, etc.)

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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How about insulin, Lipitor? Is there a glut of coffee, alcohol? http://well.blogs.nytimes.com/2013/08/12/ a-glut-of-antidepressants/?_r=0

http://psychcentral.com/blog/archives/2013/08/19/is-a- glut-of-antidepressants-really-so-bad/

Case vignette

http://commons.wikimedia.org/wiki/File:Portrait-as-an-artist-as-a-young-man.jpg

28yo man, recently married 6m ago, appears well, but quickly breaks down: He says he’s made a terrible mistake for imposing himself on his wife. “I’m a terrible person who cheated on my wife and on my taxes.” He reports two months of depressed mood, crying spells, as well as oversleeping and not being able to get out of bed. In addition, his energy has been low, he has no appetite, and he can’t focus at work.

Would you diagnose him with Major Depressive Disorder? Would you prescribe an antidepressant?

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Case vignette

http://commons.wikimedia.org/wiki/File:Portrait-as-an-artist-as-a-young-man.jpg

“I cheated on my wife and on my taxes.” Do we accept his reasons as the causes of his depression? Even when confronted with an intuitively plausible set of reasons, we must look for

• bjective causes.

The Trap of Meaning

“Finding an explanation that appears meaningful and adopting it as causal.”

Lyketsos CG, Chisolm MS. The trap of meaning: a public health

• tragedy. JAMA. 2009 Jul 22;302(4):432-3. doi: 10.1001/jama.

2009.1059.

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"...humans are incredibly good at linking cause and effect—sometimes too good..."

"... it means that when you see something occur in a complex adaptive system, your mind is going to create a narrative to explain what happened—even though cause and effect are not comprehensible in that kind of system."

Embracing Complexity, An interview with Michael Mauboussin by Tim Sullivan Harvard Business Review 2011

https://hbr.org/2011/09/embracing-complexity/

Reason vs. Cause

• “Reason" and "cause" are not

contradictory, nor are they synonymous

• Confusion between them: delays

mental health care for mood disorders much more than care for diabetes, heart disease, stroke and cancer (?)

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Does the Trap of Meaning

• ccur with mania or

hypomania?

Yes!

Trap of Meaning references:

Kendler KS, Gardner CO. Dependent Stressful Life Events and Prior Depressive Episodes in the Prediction of Major Depression: The Problem of Causal Inference in Psychiatric Epidemiology. Arch Gen Psychiatry. 2010;67(11):1120-1127. ¡ ¡ Kendler KS, Myers J, and Halberstadt LJ. Do reasons for major depression act as causes? ¡Molecular Psychiatry (2011) 16, 626–633; doi:10.1038/mp. 2011.22; published online 8 March 2011. ¡ ¡ Kendler KS, Myers J, and Halberstadt LJ. Should the Diagnosis of Major Depression made Independent of or Dependent upon the Psychosocial Context? Psychol Med. 2010 May ; 40(5): 771–780. doi:10.1017/ S0033291709990845. ¡

Lyketsos CG, Chisolm MS. The trap of meaning: a public health tragedy. JAMA. 2009 Jul 22;302(4): 432-3. doi: 10.1001/jama.2009.1059. ¡

¡

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What are the Validated Risk Factors for Depression? Take Home Message

Be aware of "explaining away" mood episodes.

Lyketsos CG, Chisolm MS. The trap of meaning: a public health tragedy. JAMA. 2009 Jul 22;302(4):432-3. doi: 10.1001/jama.2009.1059.

http://jama.jamanetwork.com/article.aspx?articleid=184281

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Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

Case Vignette

PMDD

How would you differentiate between PMDD and depression?

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Normal PMS vs. PMDD

Normal PMS (Premenstrual Syndrome):

• 80% of women
• Mild to moderate emotional fluctuations

PMDD (Premenstrual Dysphoric Disorder):

• 3-8% of women
• Severe moods swings, depressed mood,

irritability

Wittchen HU et al. Prevalence, incidence and stability of premenstrual dysphoric disorder in the community. Psychol Med 2002 Jan;32(1):119-32.

Premenstrual dysphoric disorder

• Must begin in the week before menses and

improve within a few days after onset of menses and then be absent in the week postmenses.

• Criteria must be confirmed by prospective

daily ratings during at least 2 consecutive symptomatic menstrual cycles.

• Not simply premenstrual exacerbations of
• ther psychiatric d/o’s

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Menstrual Cycle Week and All Psychiatric Admissions

If random, admissions

• f women to

psychiatric hospitals for all psychiatric diagnoses would be 25% on each week of the menstrual cycle

10 20 30 40 50 60 70 1st 2nd 3rd 4th Hospital Admits

Week of Menstrual Cycle

• Luggin et al. “Acute psychiatric admission related to the menstrual cycle.” Acta Psychiatrica Scandinavica, Vol 69, Issue 6, pp

461–465, June 1984.

• Targum et al. “Menstrual cycle phase and psychiatric admissions.” , J Affect Disord. 22(1-2):49-53, May-Jun 1991.

Disorders with Premenstrual Exacerbation (PME)

Psychiatric

• Affective disorders
• Anxiety disorders
• Psychotic disorders
• Eating disorders
• Personality disorders
• Substance abuse

General Medical

• Migraine
• Allergies
• Asthma
• Seizures

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Women and Depression

• More likely to present with atypical

symptoms and anxiety

• More likely to respond to ssri’s (?higher

plasma levels of sertraline)

• Less likely to respond to TCAs (?more

likely to experience ADRs to TCAs) Keers R and Aitchison KJ. Gender differences in antidepressant drug response. Int Rev Psychiatry 2010; 22(5):485-500.

Premenstrual Dysphoric Disorder Treatments

Two Main Treatments

• SSRI’s
• Hormones

“Be the you he likes. Good to be around, any day of the month.”

This is so wrong!

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https:// www.midol.com/ midol-products/ Accessed 6/13/15

A tangent on Midol (which is for PMS not PMDD)

Midol formulation Active ingredients

Midol Complete Acetaminophen 500 mg Caffeine 60 mg Pyrilamine Maleate 15 mg Menstridol, formerly

known as "Extended Relief"

Naproxen Sodium 220 mg "Teen" Acetaminophen 500 mg Pamabrom 25 mg (8-bromotheophylline) “PM” Acetaminophen 500 mg Diphenhydramine citrate 38 mg

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Possible PMDD Treatments

Antidepressants

• SSRI*
• SNRI*

Clomipramine** Anxiolytics Benzodiazepines** Buspar** Ovulation Suppression OCPs* GnRH Agonists (leuprolide,

nafarelin, goserelin)**

Danazol (inhibits LH/FSH) Oophorectomy Other Exercise Vit B6 Calcium** NSAIDS CBT* Diet Chasteberry

(may reduce FSH or Prolactin)

**studies for PMS *studies for PMDD

SSRI’s in PMDD Fluoxetine, Sertraline and Paroxetine CR are FDA approved for PMDD Intermittent dosing ok*

*Cohen LS, et al. Obstet Gynecol. 2002; 100: 435-444.

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What about hormone therapy? Lower progestin potency:

Ortho Evra patch Ovcon 35 Ortho-TriCyclen Othro-Cyclen Brevicon Modicon Necon 1/35 Alesse Levlite Tri-Levlen Triphasil Trivora

• Rohr, UD. “The impact of testosterone imbalance on depression and women's health.” Maturitas. 2002

Apr 15;41 Suppl 1:S25-46.

Yaz: Drospirenone 3.0mg, FDA approved for PMDD

Menstrual Cycle

Nillni YI etal. Anxiety sensitivity, the menstrual cycle, and panic disorder: a putative neuroendocrine and psychological interaction. Clin Psychol Rev 2011 Nov;31(7):1183-91.

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Which hormones are good for mood?

• In general, try to lower progestin
• Monophasic OCP (eg, Seasonale) taken

continuously can stabilize mood

• Women who are sensitive to hormonal

fluctuation should avoid triphasic OCP’s

• It takes about 2 cycles to see if a certain

OCP will work

PMDD References

Lopez LM et al. Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev 2009 Apr 15; (2):CD006586. Freeman et al. An overview of four studies of a continuous oral contraceptive (levonorgestrel 90 mcg/ethinyl estradiol 20 mcg) on premenstrual dysphoric disorder and premenstrual syndrome. Contraception 2012 May;85(5):437-45. Steiner M and Pearlstein T. Premenstrual dysphoria and the serotonin system: pathophysiology and treatment. J Clin Psychiatry 2000;61 Suppl 12:17-21.

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PMDD In Summary

• PMDD: 3-8% of women
• Etiology: ?hypersensitivity to the change

in estrogen and progesterone

• Not simply premenstrual exacerbations
• Treatments:

– SSRIs daily or luteal phase dosing – Ovulation suppressing OCPs (more second line)

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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11-year-old Max.

• Since infancy, flew into a rage at the

smallest of slights, such as being told "no."

• Sent one child to the hospital during a

play session, and has drawn blood a few other times At age 4, Max was diagnosed with bipolar disorder. 60% or so of children who are likely candidates for the new diagnosis are currently diagnosed with bipolar disorder.

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The Wall Street Journal, By SHIRLEY S. WANG Updated Oct. 18, 2012 10:34 p.m. Accessed 6/14/15

Disruptive Mood Dysregulation Disorder Criteria

• Severe recurrent temper outbursts

– not developmentally appropriate

• On average, outbursts are ≥ 3x/wk
• Inter-episode mood is typically irritable,

corroborated by others

• ages 6-18 only; onset must be before age

10

• no more than 1d of mania/hypomania

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DMDD – Bottom Line

• Severe recurrent temper outbursts in

children

• Previously diagnosed with bipolar

disorder

• Still more information to come…

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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Case Vignette

72yo man is depressed in the context of the death

• f his wife.

How would you differentiate between grief and depression?

No Bereavement in DSM-5

No Bereavement exclusion in DSM-5 Grief is still exists Mild depressive episodes can be treated with psychotherapy alone

http://www.dsm5.org/Documents/Bereavement%20Exclusion %20Fact%20Sheet.pdf

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Depression vs. Grief Case Vignette

72yo man is depressed in the context of the death

• f his wife.

How long would you wait before diagnosing MDD? a) Two weeks b) One month c) Two months d) Four months e) Six months f) One year or more

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Depression vs. Grief

• Beware the Trap of Meaning!
• Individuals who fulfill MDD criteria

after loss of significant other have NOT been shown to recover at a greater rate than MDD alone

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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Case Vignette

71yo man complains of poor memory and depressed mood.

How would you differentiate between dementia and depression?

Major Depressive Episode: SIG E CAPS criteria

Depressed mood (or anhedonia), plus: S –Sleep symptoms I—lack of Interest. G—feelings of Guilt E—lack of Energy. C--lack of Concentration. A--lack of Appetite. P--Psychomotor changes S--thoughts of Suicide

32 Major Neurocognitive Disorder Cognitive impairment due to depression Insight Not aware Aware and concerned Course Slow, often subtle (onset

• ver month/years)

More rapid(onset over days and weeks) Social skills Maintained Lost Memory Loss of recent, not remote memory. Random memory loss Effort Fair Poor, or variable

*May not be distinguishable, or may be co-morbid

Montreal Cognitive Assessment Test (MoCA)

Google: “Mocatest.org”

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Montreal Cognitive Assessment Test (MoCA)

Use instructions

MOCA (vs. MMSE)

• Both are screening tools
• Slightly more difficult, about 10min
• More sensitive, particularly for early

AD, and neurological disorders (eg, Parkinson’s)

• Includes tasks such as a clock-

drawing test and a trail test

• Three versions
• Free

Reference: Nassreddine et al, 2005

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Dementia vs. Depression

• Depression requires either sad mood
• r anhedonia
• Depression may be the “prodrome”
• f dementia
• Depression, even the context of

dementia, may respond well to antidepressants or behavioral activation/socialization

Update on Mood Disorders Outline

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder

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Case Vignette 35yo man

• Presents to your outpatient clinic with

depressed mood, anhedonia, low energy, sleeping 12-14 hours per day, for the past four weeks

• How would you rule out bipolar disorder?

69 70

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List DSM criteria for Mania/ hypomania

Reminder for Bipolar Disorder: DIG FAST Mnemonic*

D – Distractibility I – Insomnia G – Grandiosity (or inflated self esteem) F – Flight of Ideas (or racing/crowded thoughts) A – Activities (increased goal directed activities) S- Speech (pressured) T- Thoughtlessness (impulsivity, ie, increased pleasurable activities with potential for negative consequences: sex, money, traveling, driving) *need 3 for elevated mood, 4 if mood is only irritable

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Subtypes of Bipolar Disorder

Bipolar I: Depressive episodes plus manic episodes Bipolar II: Depressive episodes plus hypomanic episodes “Bipolar III”: Antidepressant Associated Mania/Hypomania

Dysthymic Disorder Major Depressive Disorder Cyclothymic Disorder Bipolar I Disorder Bipolar II Disorder

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Typical (MINI) screening question

“Have you ever in your life ever felt unusually elevated or irritable?”

Obstacles to correct assessment and diagnosis of bipolar disorder

• clinician lack of familiarity with bipolar

disorder

• relative rarity of mania
• disinclination to see doctor when manic or

hypomanic

• phenomenon of Trap of Meaning
• poor recall by patients
• absence of collateral information

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We need lots of information:

Several risk factors are associated with conversion:

• Age of onset (ie,

<25yo)

• Family history of

bipolar disorder

• Number of depressive

episodes (ie, > six)

• Post-partum onset
• Psychotic features
• Severity (eg, hospital

admission) Other important information:

• Triggering events
• Prodrome
• Treatments: efficacy

and adherence

• Number of episodes
• Course
• Baseline functioning

Problem: The database is Gi-Normous, how do we cover it all?

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Life Course Method: Get a Story

Start from the beginning of patient’s history of mood/psychiatric problems. Using life events, divide history in to epochs of time Go chronologically forward with each epoch, with special attention to mood episodes and significant life events For each mood episode, obtain prodromal symptoms, medications tried and their efficacy, adherence to medications. Obtain collateral information

Diagnostic Criteria Compared

Hypomanic Episode: Manic Episode A. at least 4 days. at least 1 week B. See DIGFAST same C. unequivocal change

• D. observable by others.
• E. not severe enough to cause marked

impairment

• C. marked impairment or

hospitalizaton or psychosis F . are not due to … a substance … or a general medical condition

• D. are not due to … a

substance … or a general medical condition Key point:

Marked impairment is enough to qualify for a diagnosis of mania

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Bipolar Disorder Symptoms Are Chronic and Predominantly Depressive

Study 1

Asymptomatic Depressed Hypo/manic Cycling/mixed % of Weeks 146 Bipolar I Patients followed 12.8 yrs 86 Bipolar II Patients followed 13.4 yrs

Study 2

6% 9% 32% 53% 46% 50% 2% 1%

• 1. Judd LL, et al. Arch Gen Psychiatry 2002.59:530-537.
• 2. Judd LL, et al. Arch Gen Psychiatry 2003;60:261-269.

Tip#1: Focus on Prodrome

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If multiple episodes, obtain:

Overall number Frequency Typical course Most recent episode

Keep interview moving, don’t get bogged down!

Tip#2:Obtain only as much info as you need. Advanced tip#3: Quote the patient

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Tip#4: Find the kryptonite! Tip#5: Practice!

Li, D. Current Issues in Bipolar Disorder Diagnosis: The Life Course Method. The Carlat Report 2012 July/August 8:5-12. http://www.thecarlatreport.com/ free_articles/current-issues-bipolar- disorder-diagnosis-life-course-method-free- article

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Bipolar Depression Treatment

• Typical pattern is M-D-E:

– Prevent Mania

• Avoid antidepressants
• Prevent Mania

Update on Mood Disorders Summary

• Overview and Diagnostic criteria
• Trap of Meaning
• Premenstrual Dysphoric Disorder
• Disruptive Mood Dysregulation

Disorder

• Bereavement/Grief
• Dementia (Major Neurocognitive

Disorder)

• Bipolar Disorder