Reactive or Endogenous … Does it Matter?

Major Depressive Disorder

Tom Janzen, M.D.

London, Ont

May 1, 2014

• Recognize that MDD is heterogeneous

and as such optimizing outcomes requires

individualizing care plan

• Understand that functional recovery requires a full

appreciation of psychosocial, physical as well as mental

health issues

• Identify and explore solutions for helping disabled

workers regain mental health

Learning Objectives

• Health

◦ “… a state of complete physical, mental and social

well-being and not merely the absence of infirmity”

• Mental Health

◦ “… a feeling of well-being in which the individual

realizes his/her own abilities, can cope with normal

stresses of life, can work productively and fruitfully,

and is able to make contributions to his or her

community”

WHO Definitions

• DSM IV-TR (1992-2013)

◦ “A mental disorder is a clinically significant

behavioral or psychological syndrome or

pattern that occurs in an individual and that is

associated with present distress or disability or

with a significantly increased risk of suffering,

death, pain, disability, or an important loss of

freedom.”

Defining Mental Illness

• DSM 5 (May 16, 2013 -)

◦ "A mental disorder is a syndrome

characterized by clinically significant

disturbance in an individual's cognition,

emotion regulation, or behavior that reflects a

dysfunction in the psychological, biological, or

developmental processes underlying mental

functioning. Mental disorders are usually

associated with significant distress in social,

occupational, or other important activities.”

DSM 5 Definition of a Mental Illness

• An expectable or culturally approved response to a

common stressor or loss, such as the death of a loved one

• Socially deviant behavior (e.g., political, religious, or

sexual) and conflicts that are primarily between the

individual and society are not mental disorders unless the

deviance or conflict results from a dysfunction in the

individual

DSM 5: A Mental Illness IS NOT…

62% Canadian Employees

• Founder of Research on Stress

◦Good Stress – contributes to wellness

◦ Bad Stress – contributes to disease and

sickness

Canadian Pride: Hans Selye (1907-1982)

• Committed to Employer

◦ 1991 – 66%

◦ 2001 – 45%

• 7% Canadians off work

for MH

• Estimated 17% of wage

bill spent on mental

illness

Impact

Making the Diagnosis

Major Depressive Disorder

• Diagnosis no longer requires

differentiation

• Treatments identical

• Many clinicians remain skeptical

Reactive or Endogenous

• 43 y.o male factory worker

• 23 year history with company

• Non-work related injury (fractured tibia)

• Surgery + 3 months rehab

• Return to work but re-injures leg

• Repeat surgery with complications

• Chronic pain – off work X 9 months

Case Presentation: M.R.

• Presents with complaints of depression

• Nervous about return to work

• Restrictions from surgeon – can’t do his old job

• Financial concerns

• Marital strain

M.R.

Acronym for DSM 5 Criteria: MDD

SIGECAPS

Measurement Based Care

Sig: E Caps and PHQ-9

SIGECAPS PHQ-9

Core Symptoms of Depression

Depressed Mood

Sleep decreased

Interest decreased in activities (anhedonia)

Guilt or worthlessness

Energy decreased

Concentration difficulties

Appetite disturbance or weight loss

Psychomotor retardation / agitation

Suicidal thoughts

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American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 2000:352.

Ohayon MM, et al. J Clin Psychiatry 2004;65[suppl 12]:5–9

BCMJ, Vol. 44, No. 8, October 2002, page(s) 415-419

Measurement Based Care

HAM-D 7 and Sig: E Caps

SIGECAPS HAMD-7

Core Symptoms of Depression

Depressed Mood

Sleep decreased

Interest decreased in activities (anhedonia)

Guilt or worthlessness

: Associated Symptoms

Energy decreased

Concentration difficulties

Appetite disturbance or weight loss

Psychomotor retardation / agitation

Suicidal thoughts

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, 2000:352.

Ohayon MM, et al. J Clin Psychiatry 2004;65[suppl 12]:5–9.

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Other Scales to Identify Additional Symptoms

GAF to WHODAS: Assessing Function

PLANNING CARE

Patient Factors

Quality Safety Health Care 2002;11:214–218

Severity of Illness

Patient Preference

Medication Side Effects

Cultural and Spiritual beliefs

Motivation

Willingness to participate in Care Planning

Family History

RA

TIO

NA

LE

Planning Care: Patient Factors

What to Consider

Planning Care: Resource Availability

Resource Intensity

Bower et al. BMJ 2013;346:f540

Hospitalization, ECT, rTMS, DBS

Medications

Live Psychotherapy

Internet Resources

Books, Self Help, Videos

Low Resource

Intense

Interventions

High Resource

Intense

Interventions

https://moodgym.anu.edu.au

Talk Meds Combo

Planning Care:

Talk Therapy, Medications or Both

Do they help you decide?

TREATMENT GUIDELINES

• What is your best therapeutic choice?

• What is the impact of comorbid psychiatric or medical

conditions, psychosocial factors?

• Age, gender differences: do they matter?

• How well do guidelines reflect my clinical practice?

Treatment Guidelines: Do they help you decide?

J Couns Psychol. 2012 Jan;59(1):134-49. Epub 2011 Oct 24

• Depression duration <4 weeks or >24 months

• Another comorbid Axis I disorder

• Borderline Personality Disorder

• Dysthymic Disorder

• Bipolar disorder

• Psychotic features

• Insufficient symptom severity

• Substance abuse in prior 6 months

• Suicidal ideation

• Comorbid anxiety

Problem... these issues are also common in ‘real world’ patients!

Zetin & Hoepner. J Clin Psychopharmacol 2007; 27: 295-301.

Top 10 Exclusion Criteria in Antidepressant RCTs

Medication Choices

MAJOR DEPRESSIVE DISORDERCANADIAN GUIDELINES

Canadian Guidelines

First Line Antidepressants

Medication Required?

12 Choices: First Line Equal Efficacy

Level1 Evidence

Created by Tom Janzen, M.D.

R.W. Lam et al. Journal of Affective Disorders 117 (2009) S26–S43

How do you

decide?

MATCHING PATIENT COMPLAINTS TO NEUROBIOLOGY

DSM 5Core Symptoms

5-HT NE DAImportant Brain Regions

Involved in MDD symptoms

Depressed Mood VMPFC, A VMPFC, A VMPFC, A• Prefrontal Cortex (PFC)

• VentroMedial (VMPFC)

• DorsoLateral (DLPFC)

• Orbital (OFC)

• Basal Forebrain (BF)

• Hypothalmus (Hy)

• Thalmus (Th)

• Spinal Cord (SC)

• Nucleus Accumbens (NA)

• Striatum (S)

• Cerebellum (C)

• Amygdala (A)

SleepPFC, BF, Hy,

ThPFC, BF, Hy,

ThPFC, BF, Hy,

Th

InterestApathy

PFC, Hy PFC, Hy, NA

GuiltWorthlessness

VMPC, A

Energy PFC, SC PFC, S, NA

ConcentrationExec. Function

DLPFC DLPFC

Appetite/Weight Hy

PsychomotorAgitation orRetardation

PFC, NA, S PFC, C PFC, NA, S

SuicideVMPFC, OFC, A

Linking Symptoms and Circuits

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Adapted from Stephen Stahl, Essential Psychopharmacology, March 2008Created by Tom Janzen, M.D.

Associated Symptoms

5-HT NE DAImportant Brain Regions

Involved in MDD symptoms

Anxiety PFC, A, Th, S

• Prefrontal Cortex (PFC)

• VentroMedial (VMPFC)

• DorsoLateral (DLPFC)

• Orbital (OFC)

• Basal Forebrain (BF)

• Hypothalmus (Hy)

• Thalmus (Th)

• Spinal Cord (SC)

• Nucleus Accumbens (NA)

• Striatum (S)

• Cerebellum (C)

• Amygdala (A)

Pain PFC, Th, SC PFC, Th, SC

Sexual Dysfunction

NA, SC

Sleepiness/ Hypersomnia

PFC, BF, T, Hy

PFC, BF, T, Hy

Vasomotor Hy Hy

Associated Symptoms: Commonly Seen in MDD

Adapted from Stephen Stahl, Essential Psychopharmacology, March 2008Created by Tom Janzen, M.D.

DSM 5

Core Symptoms5-HT NE DA PHQ -9 Questionnaire

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Interest/Apathy 1. Little interest or pleasure in doing things 0 1 2 3

Depressed Mood 2. Feeling down, depressed, or hopeless 0 1 2 3

Sleep3. Trouble falling or staying a sleep, or

sleeping too much0 1 2 3

Energy 4. Feeling tired or having little energy 0 1 2 3

Appetite/Weight 5. A or B A. Poor appetite 0 1 2 3

B. Overeating 0 1 2 3

Guilt

Worthlessness

6. Feeling bad about yourself—or that you are

a failure or have let yourself or your family

down

0 1 2 3

Concentration

Exec. Function7. Trouble concentrating on things, such as

reading the newspaper or watching tv0 1 2 3

Psychomotor Agitation or

Retardation8. A or B

A. Moving or speaking so slowly

that other people could have

noticed. 0 1 2 3

B. Being so fidgety or restless that

you have been moving around a lot

more than usual0 1 2 3

Suicide9. Thoughts that you would be better off dead,

or of hurting yourself in some way0 1 2 3

Adapted from Stephen Stahl, Essential Psychopharmacology, March 2008

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Current Symptoms:

Connecting Neurotransmitters and Scales

Created by Tom Janzen, M.D.

Associated Symptoms

5-HT NE DA Possible Questions to Ask

Anxiety Experience anxiety and worry about the future

Pain

Experiencing pain of unknown origin or excessively worried about their pain (back

pain, muscle or joint pain, headaches, stomach pain, etc.)

Sexual DysfunctionLow sexual interest, difficulty achieving

orgasm, decreased satisfaction

Sleepiness/ Hypersomnia

Tired all day and fall asleep at any tme

Vasomotor Symptoms

(perimenopausal)

Prominent hot flushes more pronounced than similar aged friends

Consider Associated Symptoms of Depression

Adapted from Stephen Stahl, Essential Psychopharmacology, March 2008Created by Tom Janzen, M.D.

• Marriage breakup

• Financial stressors

• Substance abuse

• Friendships/relationships

• Concerns re physical health

Consider Life Circumstances:How does this impact treatment considerations?

Circuits and Side Effects

Adapted from Stephen Stahl, Essential Psychopharmacology, March 2008, Clinical Handbook of Psychotropic Drugs

R.W. Lam et al. Journal of Affective Disorders 117 (2009) S26–S43

Adapted from Virani et al. Clinical Handbook of Psychotropic Drugs Online 2012.

• Dyspepsia, nausea, headaches, nervousness, akathesia, EPS, anorexia, sexual side effects

5HT Reuptake Transporter

Blockade

• Tremors, tachycardia, hypertension, sweating, insomnia, erectile and ejaculatory problems

NE Reuptake Transporter

Blockade

• Psychomotor activation, aggravation of psychosisDA Reuptake Transporter

Blockade

• Hypotension, ejaculatory problems, sedation, weight gain (5HT2C)

5HT2A Receptor Blockade

• Dry mouth, blurred vision, constipation, urinary retention, tachycardia, memory disturbances, sedation, glaucoma

M1 Receptor Blockade

• Sedation, postural hypotension, weight gainH1 Receptor Blockade

• Helping patients achieve functional recovery requires a

coordinated care plan developed in conjuction with your

patient

• Rational choices should be made using knowledge of

your patients physical, mental and psychosocial

circumstances

• Understanding how symptoms of depression link to brain

circuits can help inform medication choices

Summary