Ronald A. Remick, MD, FRCP(C)

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An Overview and Update on Mood Disorders 2013

• Ronald A. Remick, MD, FRCP(C)
• Medical Director, Mood Disorder Association of
  British Columbia
• email rremick_at_shaw.ca
• Sophia I. Zisman, Bsc Hons.
• St. Georges University of London

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Overview of depression

1. Depression affects one out of five Canadians
2. Lifetime prevalence of major depression-8
3. - minor depression/dysthymia 7
4. - bipolar I/II - 2
5. 3. 1.4 million Canadians afflicted at any one time

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Depressive disorders have a significant morbidity

1. 83 billion in direct medical costs/25 billion
   in associated medical costs
2. 1,000,000 person-years lost from work
3. Second leading medical cause of long term
   disability
4. Forth leading cause of global burden of disease

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Absenteeism vs. Presenteeism

• Presenteeism (lost productivity while at work)
  likely a more significant problem with mood
  disorders than previously recognized in Canada
• Productivity loss from presenteeism due to
  depression is 4 hours/week while loss from
  absenteeism is but 1 hour/week (between 6
  billion loss per annum)!

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What Causes Depression?
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Genetics

• About one third of the variance in major
  depression is related to hereditary factors (in
  bipolar illness it is likely two thirds)
• What is inherited (e.g. brain biological changes,
  personality traits, etc) is yet to be determined.
• Early-onset (before age 30), severe, recurrent
  depression more likely to have a genetic basis.
• No single gene but likely a complex multi-gene
  inheritance.

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Personality/ Temperament

• Individuals with the normal personality traits
  avoidance of harm, anxiousness, and pessimism -
  are slightly more at risk to develop a depressive
  illness.
• To a large degree, many personality traits are
  inherited.
• How significant this cause of depression is,
  and the relationship between genetics (nature)
  and/or the environment (nurture) remains unclear.
  

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Environment/Psychological Adversity

• The effects of stress/adversity dependent
• The timing of the stressor (prenatal, postnatal,
  late life)
• Severity of the stressor
• Repetition of the stressor
• Stress may be more important in
• The genetically vulnerable
• Lack of social support
• Resiliency genetic versus learning

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Brain Chemical Changes

• The Monoamine Hypothesis
• Depression is caused by the underactivity in the
  brain of monoamines such as dopamine, serotonin
  and norepinephrine (in reality a lot more
  chemicals may be involved).
• Mania is caused by the overactivity of these
  monoamines in the brain.
• The monoamine hypothesis forms the basis of the
  pharmaceutical treatment of depression

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Depression - Mortality

• 4 of all depressives die by their own hands
• 66 of all suicides are preceded by depression
• Depression cardiovascular disease
• Risk of MI 4-5x higher in MDD
• Depression is biggest risk factor post MI

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Depression is a factor in more than 65 of
successful suicidesalways be aware, always ask
about suicide.
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Assessing suicide risk

1. ask, ask, ask! ?thoughts of death/suicide
   ?plan?method?means ?said goodbyes/written
   note ?what would precipitate or prevent
2. Assess risk factors

• First nations
• Male
• Advanced age
• Single/living alone
• Previous attempt
• Family hx of suicide
• Psychotic
• Hopeless
• Concomitant medical illness
• Substance abuse

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Detecting depression

• 1. Individuals at High Risk
• chronic insomnia or fatigue, chronic pain,
  multiple somatic complaints (thick charts),
  chronic medical illness (RA, DM), acute cardiac
  events, recent trauma, family history of
  depression, previous episodes
• 2. Special Population
• children/adolescents -irritable mood geriatric
  grief certain cultures- physical symptoms

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Diagnosis of depression

1. A distinct mood change (depressed, irritable,
   anxious, etc) for at least two weeks
2. Four or more SIGECAPS

Sleep Interest Guilt Energy Concentratio
n Appetite Psychomotor Activity Suicide
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Screening Questions

• in the last month, have you been bothered by
  little interest or pleasure in doing things?

what about feeling down, depressed or hopeless?
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Health Screening Questionnaire

• Patient Health Questionnaire PHQ-9
• (www.pfizer.com/PHQ/9)

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Depression vs. Dysthymic Disorder

• Major Depression
• 1. depressed mood and gt4 SIGECAPS
• 2. two week duration
• Dysthymic Disorder
• 1. depressed mood and 2 or 3 SIGECAPS
• 2. TWO YEAR duration

The treatment for MDD and dysthymia are identical
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Collateral information and collaboration with
family is paramount in the successful treatment
of mood disorders.
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There is a plethora of self help, patient
directed resources for understanding and treating
depressive disorders use them.
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Physician and patient resources
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Depression The Good News

• Expect full recovery (with treatment) in 65
• Expect marked improvement in 25.
• Less than 10 have a protracted chronic course of
  illness

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The most common cause of a failed treatment
intervention in depression is non compliance.
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Effective treatments for mood disorders can be
either psychological or biologicaland
combination of both is ideal
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Cognitive Behavioral Therapy (CBT) is an
effective intervention for mild/moderate
majordepression.
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Accessibility
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Acute Treatment Antidepressants

• The use of antidepressants should be accompanied
  by clinical management, including patient
  education, attention to adherence issues, and
  self- management techniques.
• Choose a specific antidepressant based on
• -your comfort/familiarity level
• -patients previous good/poor response
• -side effects
• -cost
• -drug-drug interactions
• -co morbid conditions
• -depressive subtype

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Antidepressants
First Line Usual Dose Cost ()
SSRI SSRI SSRI
Citalopram (Celexa) 20-40mg 1.3-2.6
Fluvoxetine (Prozac) 20-40mg 1.0-2.0
Fluvoxamine (Luvox) 100-200mg 0.9-1.8
Paroxetine (Paxil) 20-40mg 1.8-3.5
Sertraline (Zoloft) 50-200mg 1.2-2.4
RIMA RIMA RIMA
Moclobemide (Manerix) 300-600mg 1.3-1.8
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Antidepressants
First Line Usual Dose Cost ()
SNRI SNRI SNRI
Venlafaxine (Effexor) 75-225mg 1.7-3.4
Duloxetine (Cymbalta) 60-120mg
Desvenlafaxine (Pristique) 50-100mg
Novel Action Novel Action Novel Action
Bupropion (Wellbutrin) 150-300mg 0.8-3.7
Mirtazapine (Remeron) 30-60mg 1.3-2.6
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Antidepressants
Second line Usual Dose Cost ()
TCA TCA TCA
Amitriptyline (Elavil) 100-250mg 0.04-0.1
Clomipramine (Anafranil) 100-250mg 0.8-2.1
Desipramine (Norpramin) 100-250mg 0.8-2.0
Imipramine (Tofranil) 100-250mg 0.04-0.1
Nortriptyline (Aventyl) 75-150mg 0.8-1.6
Trimipramine (Surmontil) 75-150mg
Maprotiline (Ludiomil) 75-150mg
Antipsychotics
Quetiapine

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Third Line Usual Dose Cost ()
MAOI MAOI MAOI
Phenelzine (Nardil) 30-75 mg 03-0.9
Tranylcypromine (Parnate) 20-60mg 0.4-0.8
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Acute Treatment -Antidepressants

• To promote adherence, ALL patients should be told
  
• Antidepressants are not addictive
• Take the medicine every day
• It may take 2-4 weeks before you notice
  improvement
• Mild side effects are common, but usually
  temporary
• Do not stop meds even if feeling better
• Call doctor if any questions

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Antidepressants - Response
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Managing Poor/Incomplete Antidepressant Response

• If no response (lt20) after 3-4 weeks, then raise
  the dose incrementally every week to maximum
  tolerated if still no response
• Re-evaluate diagnostic issues (bipolar,
  medical/psych comorbidity, substance abuse,
  personality disorder)
• Reassess treatment issues (compliance, side
  effects)
• Consider SWITCH (if lt 30 response) to different
  drug (another SSRI or different class) or AUGMENT
  (if gt30 response).

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Augmentation strategies are effective and easy to
useand are currently underutilized in the
medical treatment of major mood disorders.
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Antidepressant Augmentation

• rationale 30 response in 2 weeks
• lithium 150mg bid x 5d and increase by 300mg
  5d to 450 bid for 10d trial
• cytomel 25ugm x 5d, 50ugm for 10d trial
• dextroamphetamine 2.5-5mg qam increase by
  2.5-5mg q 3d to max 10mgqam 5mg_at_noon for 7d
  trial
• atypical antipsychotics (olanzapine 5-10mg,
  aripiprazole 1-4mg)

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Two adequate trials of serotonin reuptake
inhibitors (SRIs) are enoughconsider
venlafaxine/duloxetine as an SRI in your
treatment schema.
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Maintenance therapy with antidepressants

• Continue the same dose of the antidepressant
  after successful treatment for at least 6-9
  months.
• Consider long term/indefinite treatment
• Two or more serious episodes in less than five
  years.
• Episodes that have been present for gttwo years
  before successful treatment.
• Patients who have their first episode after the
  age of 50.
• Severe (suicidality/ psychosis)

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Other Treatments for Major Depressive Disorders

• Electroconvulsive therapy (ECT)
• Phototherapy (light box)
• Transcranial magnetic stimulation(TMS)
• Vagal nerve stimulation (VNS)
• Deep brain stimulation (DBS)

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Depressive Temperament vs. Medical Syndrome

• Borderline personality disorder (BPD) (affective
  instability with reactivity of mood with intense
  dysphoria, irritability, anxiety chronic
  feelings of loneliness excessive inappropriate
  anger impulsive suicide attempts) the key to
  the differential diagnosis is BPD mood swings
  lasts hours, rarely days.