An Overview and Update
on Mood Disorders – 2013
Ronald A. Remick, MD, FRCP(C)
Medical Director, Mood Disorder Association of British
Columbia
email : rremick@shaw.ca
Sophia I. Zisman, Bsc Hons.
St. George’s University of London
Overview of depression
①
②
Depression affects one out of five Canadians
Lifetime prevalence of major depression-8%
①
- bipolar I/II - ~2%
3. 1.4 million Canadians afflicted at any one
time
②
③
- minor depression/dysthymia – 7%
Depressive disorders have a
significant morbidity
①
②
③
④
$83 billion in direct medical costs/$25 billion in
associated medical costs
1,000,000 person-years lost from work
Second leading medical cause of long term
disability
Forth leading cause of global burden of disease
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)!
What Causes Depression?
Brain Chemical
Changes
Genetic
Causes of
Depression
Psychological
Adversity/Environment
Personality/
Temperament
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.
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.
Environment/Psychological
Adversity
•
The effects of stress/adversity dependent:
a.
b.
c.
•
Severity of the stressor
Repetition of the stressor
Stress may be more important in:
a.
b.
•
The timing of the stressor (prenatal, postnatal, late life)
The genetically vulnerable
Lack of social support
Resiliency: genetic versus learning
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
Depression - Mortality
①
②
③
4% of all depressives die by their own hands
66% of all suicides are preceded by depression
Depression & cardiovascular disease:
I.
Risk of MI 4-5x higher in MDD
II. Depression is biggest risk factor post MI
Depression is a factor in more
than 65% of successful
suicides…always be aware,
always ask about suicide.
Assessing suicide risk
①
②
•
•
•
•
•
ask, ask, ask! : ?thoughts of death/suicide;
?plan;?method;?means; ?said
goodbyes/written note; ?what would
precipitate or prevent
Assess risk factors:
First nations
Male
Advanced age
Single/living alone
Previous attempt
•
•
•
•
•
Family hx of suicide
Psychotic
Hopeless
Concomitant medical illness
Substance abuse
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
Diagnosis of depression
A distinct mood change (depressed,
irritable, anxious, etc) for at least two
weeks
② Four or more SIGECAPS
Sleep
Concentration
Interest
Appetite
Guilt
Psychomotor
Energy
Activity
Suicide
①
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?”
Health Screening Questionnaire
Patient Health Questionnaire PHQ9
(www.pfizer.com/PHQ/9)
Depression vs. Dysthymic
Disorder
Major Depression:
1. “depressed” mood and >4+ 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
Collateral information and collaboration
with family is paramount in the
successful treatment of mood
disorders.
There is a plethora of self
help, patient directed
resources for
understanding and treating
depressive disorders – use
them.
Physician and patient
resources
CANMAT Guidelines
http://www.canmat.org/res
ources/CANMAT
Patients : depression
toolkit:
www.carmha.ca/publicatio
ns
Informative website:www.library.nhs.uk/me
ntalhealth
www.patient.co.uk
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
The most common cause
of a failed treatment
intervention in depression
is non compliance.
Effective treatments for mood
disorders can be either
psychological or biological…and
combination of both is ideal
Cognitive Behavioral
Therapy (CBT) is an
effective intervention for
mild/moderate major
depression.
Accessibility
Private
Psychologist
Public
Resources
Online
• Not covered by medical insurance
• The majority of outpatient psychiatry
departments in hospitals offer group based
CBT which is covered by MSP funding.
Enquire at your local hospital or with your
doctor!
• www.carmha.ca/publications - ‘antidepressant skills workbook (free download)-an
outstanding self directed CBT workbook
• www.moodgym.anu.edu.au
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
-patient’s previous good/poor response
-side effects
-cost
-drug-drug interactions
-co morbid conditions
-depressive subtype
Antidepressants
First Line
Usual Dose
Cost ($)
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
300-600mg
1.3-1.8
SSRI
RIMA
Moclobemide (Manerix)
Antidepressants
First Line
Usual Dose
Cost ($)
Venlafaxine (Effexor)
75-225mg
1.7-3.4
Duloxetine (Cymbalta)
60-120mg
Desvenlafaxine
(Pristique)
50-100mg
SNRI
Novel Action
Bupropion (Wellbutrin)
150-300mg
0.8-3.7
Mirtazapine (Remeron)
30-60mg
1.3-2.6
Antidepressants
Second line
Usual Dose
Cost ($)
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
TCA
Antipsychotics
Quetiapine
Third Line
Usual Dose
Cost ($)
Phenelzine (Nardil)
30-75 mg
03-0.9
Tranylcypromine
(Parnate)
20-60mg
0.4-0.8
MAOI
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
•
Antidepressants - Response
Initial mild
Improvement
(2-4 weeks)
Good Clinical
Response
Remission of
symptoms
(4-8 weeks)
(8-12weeks)
Return to
baseline
function
Managing Poor/Incomplete
Antidepressant Response
①
②
③
④
If no response (<20%) 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 < 30% response) to different
drug (another SSRI or different class) or AUGMENT
(if >30% response).
Augmentation strategies are effective
and easy to use…and are currently
underutilized in the medical treatment
of major mood disorders.
Antidepressant Augmentation
rationale – 30% response in 2 weeks
a. lithium 150mg bid x 5d and increase by 300mg
5d to 450 bid for 10d trial
b. cytomel 25ugm x 5d, 50ugm for 10d trial
c. dextroamphetamine 2.5-5mg qam; increase by
2.5-5mg q 3d to max 10mgqam + 5mg@noon for 7d
trial
d. atypical antipsychotics (olanzapine 5-10mg,
aripiprazole 1-4mg)
Two adequate trials of
serotonin reuptake inhibitors
(SRIs) are
enough…consider
venlafaxine/duloxetine as an
SRI in your treatment
schema.
Maintenance therapy with
antidepressants
①
②
I.
II.
III.
IV.
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 >two years
before successful treatment.
Patients who have their first episode after the age of
50.
Severe (suicidality/ psychosis)
Other Treatments for Major
Depressive Disorders
•
•
•
•
•
Electroconvulsive therapy (ECT)
Phototherapy (light box)
Transcranial magnetic stimulation(TMS)
Vagal nerve stimulation (VNS)
Deep brain stimulation (DBS)
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.