Depression is common in canada
▪ Higher ....... > males (6.2%)
among adult females (10.5%)
▪ depression is High in young adults .......
aged 18-25 (17.0%)
depression is prevalent in ......
poverty and stressors
...... is a multifactorial, complex illness.
Optimal treatment
ought to be
multifactorial also, addressing
biological, psychological,
environmental, genetic factors and
social factors.
dpression
over half of patients with MDD will also meet criteria for an
......
disorder at some point; and approximately 1/3 will show
comorbidity for ......
anxiety
alcohol or drug
dependence.
What can (clinical factors) put someone at risk of major depressive disorder?
-history of depression
-psychosocial adversity
-high users of medical system
-chronic medical conditions esp; cardioV Dx, diabetes and neurological disorders
-other psychiatric conditions
-times of hormonal challenge e.g peripartum
what are the symptom factors of depression?
-unexplained physical sx
-chronic pain
-fatigue
-insomnia
-anxiety
-substance abuse
Major Depressive Disorder (MDD)
Episodic- sx dissipate over time
Recurrent-◦ Once depression occurs, future episodes
likely
◦ Average number of episodes is 4
Subclinical depression-◦ Sadness plus 3 other symptoms for 10 days
Subclinical depression
◦ Sadness plus 3 other symptoms for 10 days
◦ Significant
impairments in functioning even though full diagnostic criteria are
not met
A. Emotional signs and symptoms
“Depressed”: sad, empty, hopeless
▪ Markedly diminished or lack
of pleasure in usual activities (anhedonia).
▪ No interest in the
future.
▪ Restlessness, irritability, or crying spells.
▪
Feelings of guilt, worthlessness, helplessness, and hopelessness.
B. Physical signs and symptoms
▪ Fatigue or loss of energy.
▪ Change
in sleep patterns.
▪ Too little
▪ Too much
▪ Change in appetite and
weight.
-Decreased appetite with weight loss
- Increased appetite with weight gain
▪
Unexplained physical problems.
▪ Headaches,
stomach problems, aches and pains, etc..(somatic complaints)
C. Cognitive signs and symptoms
Depression can affect how one
thinks and what one thinks about.
▪ Lack of concentration and remembering.
▪ Difficulty in making
decisions (ambivalence;
indecisiveness).
▪ Thoughts of
death or suicide.
❖ Suicide attempts
How often do episodes occur?
Episode frequency,
duration, and
intensity vary among
individuals and can
change intraindividually over
time.
Duration of Episodes
MOST PEOPLE EXPERIENCE
FULL SYMPTOMS FOR 2-4 MONTHS
-FEWER PEOPLE EXPERIENCE FULL
SYMPTOMS FOR A
YEAR AND SOME FOR MANY YEARS
SIGECAPS
Sleep
Interests
Guilt
Energy
Concentration
Appetite
Psychomotor agitation or
slowing
Suicidal ideation
SADIFACES
Sleep – decrease or increase
Appetite – decrease or increase
Depressed mood
Interest (loss
of)
Fatigue
Anxiety or
agitation
Concentration (difficulty
with)
Esteem (feelings of worthlessness)
Suicidal Thoughts or Ideations
DSM-5 Criteria for
Major Depressive Disorder
Sad mood OR loss of interest or pleasure (anhedonia)
▪ Symptoms present nearly every day, most of the day, for
at least 2 weeks
▪ Symptoms are distinct
and more severe than a normative response to significant loss
(example grief)
PLUS four of the following symptoms
-Sleeping too much or too little
▪ Psychomotor
retardation or agitation
▪ Poor appetite and weight
loss, or increased appetite and weight gain
▪ Loss
of energy
▪ Feelings of worthlessness or excessive
guilt
▪ Difficulty concentrating, thinking, or making
decisions
▪ Recurrent thoughts of death or suicide
Diagnostic specifiers for Depression
Depression with …
◦ Psychotic features
◦
With seasonal pattern (SAD)
◦ With melancholic features
(anhedonia, lack of mood reactivity)
◦ With atypical features
(reversed physical symptoms)
◦ Postpartum
◦ With anxious
distress
◦ With catatonia – marked disturbance in motor activity
Quick Pharmacist Screen for Depression → Refer
CANMAT recommends ..
◦ Quick 2-question screen
1) “In the last month, have you been bothered by little interest
or pleasure in
doing things?” and
2) “In the last month,
have you been feeling down, depressed or hopeless?”
Red Flags to
looks for:
◦ Always ask about suicidal ideation- The WHO (2016)
estimates that about 800,000
people die annually from suicide
related to MDD.
◦ Discontinuation of treatment?
◦ Screen for
risk factors (slide 09)
Complications of Depression
▪Weight gain/obesity or on the other spectrum
significant weight loss
▪Chronic illness
▪Chronic pain – link between depression and
physical pain – share some of the same
neurotransmitters
▪Self-harm – more common in adolescents
▪Cognitive changes – “I can’t remember people’s
names!; I just can’t focus” – CBT and
mindfulness can be
helpful
▪Substance misuse
▪Suicidal ideation, suicide attempts
Suicidality
Important fact for pharmacists:
▪ People who attempt suicide by
“self-poisoning” (e.g., OTC, prescription drugs, etc) are 42 times
more likely to
die from suicide in the following 5 years.
▪ An “at risk group” for pharmacy practice.
Risk for suicide attempts to be aware of:
◦ Previous non suicidal self-harm
◦ Previous suicide
attempt
◦ Psychiatric illness
◦ Hospitalization
(psychiatric)
◦ Personality disorder
◦ Female
◦ Less
than 30 years
◦ Relationship difficulties
◦ Anxiety with
other comorbidites
Suicidality
▪ 8 attempts for every successful suicide
▪
Women > men suicide
attempts ; Men > women die of suicide
▪ Death from
suicide (most common): hanging (men); overdose (women)
With a
median 5.3-year follow-up post over-dose:
➢6.3% die (all cause)
➢1.5% die from suicide
➢0.6% die from intentional overdose
Pathophysiology of Depression
▪ Monoamine hypothesis:
▪ Changes in
neurotransmitter levels and regulation - serotonin, noradrenaline,
dopamine (SSRis, SNRis, etc)
▪ Neurotrophic
hypothesis: EXERCISE INCREASES BDNF, SO RECOMMEND
EXERCISING
▪ BDNF promotes growth and maturation of immature
neurons. Low BDNF may result in loss of monoaminergic neurons
and loss of function/atrophy of hippocampus. Increased BDNF and
exercise; ketamine (fast onset!)
▪ BDNF = brain-derived
neurotrophic factor
▪ Neuroendocrine
hypothesis:
▪ Dexamethasone suppression test does not
reduce cortisol in 50% of depressed patients; indicates that there
may be a
dysregulation in stress HPA axis and this can cause
downstream effects
▪ This dysregulation can cause thyroid
deficiency – this is observed in patients with depression
▪ Regional brain dysfunction: alterations in blood
flow and regional metabolism
▪ Monoamine hypothesis:
▪ Changes in neurotransmitter levels and regulation - serotonin, noradrenaline, dopamine (SSRis, SNRis, etc)
▪ Neurotrophic hypothesis: EXERCISE INCREASES BDNF, SO RECOMMEND EXERCISING
▪ BDNF promotes growth and maturation of immature neurons. Low BDNF
may result in loss of monoaminergic neurons
and loss of
function/atrophy of hippocampus. Increased BDNF and exercise; ketamine
(fast onset!)
▪ BDNF = brain-derived neurotrophic factor
▪ Neuroendocrine hypothesis:
-Dexamethasone suppression test does not reduce cortisol in 50% of
depressed patients; indicates that there may be a
dysregulation
in stress HPA axis and this can cause downstream effects
▪ This
dysregulation can cause thyroid deficiency – this is observed in
patients with depression
▪ Regional brain dysfunction:
alterations in blood flow and regional metabolism
Neurobiology of Depression is complex
The underlying required pathophysiology required for depression is
unknown. There may not be a single specific required
neuropathological abnormality.
decrease in synaptic plasticity leads to
decreased glutamate
▪ BDNF =
brain-derived neurotrophic factor
decreased glutamate leads to
-decrease in synaptic transmission
-increase in neuronal degeneration
stress leads to
decreased or dysfunctional BDNF (brain-derived neurotrophic factor)
MCQ – Which form of treatment is the
most rapid in its effects?
A. Use of SSRI
plus adjunctive lithium
B. CBT for depression
C. Behavioral
activation → put themselves in situations that they may not want to
go (getting
them to go to social gathering)
D. ECT →
induce tiny seizure in the brain (need seizure quality)
E. St.
Johns Wart
D. ECT → induce tiny seizure in the
MCQ – Which form of treatment is the
most rapid in its effects?
D. ECT – often
improvement within four sessions (generally three sessions a week) –
seems to
change brain chemistry and quickly reverse symptoms
(mostly reserved for TRD and catatonic
depression)
MCQ – Which form of treatment is the
most rapid in its effects?
A. Use of SSRI plus adjunctive lithium – just because you have an
adjunct does not mean it will
work quickly
B. CBT for
depression – refer to psychologist – takes time
C. Behavioral
activation – focus on using behaviors to “activate” pleasant emotions
(consider
counseling on these)
D. ECT – often
improvement within four sessions (generally three sessions a week)
– seems to change brain chemistry and quickly reverse symptoms
(mostly reserved for TRD and catatonic depression)
E. St. Johns Wart – like antidepressants – 3-6 weeks, careful of
drug interactions and sourcing.
CYP3A4 inducer
NON-PHARMACOLOGICAL +
COMPLEMENTARY MEDICINE
▪ Psychotherapy
▪ CBT
▪ Group therapy
▪ Supportive
measures
▪ Exercise? Increase BDNF
▪ Nutrition
▪
Mindfulness
▪ Behavioral activation
▪ Motivational
interviewing
▪ Light therapy (if seasonal component)
▪
NHPs/alternative medicine
PHARMACOLOGICAL + MEDICAL
TREATMENTS
▪Medications
▪ SSRIs
▪ SNRIs
▪ TCAs
▪
Bupropion
▪ +others
▪ECT (electroconvulsive therapy), TMS
(transcranial magnetic stimulation)
Phases of Treatment and Scales
ACUTE
◦ 8-12 weeks
◦ Goal:
remission and restore functioning
MAINTENANCE
◦ 6-12 months or longer
◦ Goal: return to full functioning and quality of life;
prevent recurrence
If using validated scales
◦ Symptom response: usually defined as 50% or greater reduction in
baseline score
◦ Remission: a score in the nondepressed
range
Example of validated scales (clinician-rated)
◦
Symptoms: Hamilton Depression Rating Scale
◦ Functioning:
Multidimensional Scale of Independent Functioning (MSIF)
◦
Quality of Life: Quality of Life Interview (QOLI
Canadian
Network for Mood and Anxiety Treatments
CANMAT
what are some Considerations in Your Choice…CANMAT 2016
-patient and medication factors
PATIENT FACTORS
▪Clinical features
▪Comorbidities
▪Response and side effect
history
▪Patient preference
MEDICATION FACTORS
▪Comparative efficacy
▪Comparative tolerability
▪Potential
interactions with other meds
▪Simplicity of use
▪Cost and availability
SYMPTOM MATCHING
INSOMNIA → mirtazapine and paroxetine (not first line, but might help
with need for
sedation)?
SUICIDAL IDEATION/OVERDOSE
RISK/ELDERLY → avoid TCAs (can be fatal in overdose)
NEUROPATHIC
PAIN → duloxetine (SNRI)? (efficacy/indication for neuropathic
pain)
PREGNANCY → sertraline, fluoxetine?
AVOIDANCE OF
SEXUAL DYSFUNCTION → strong history of prior sexual side effects →
Bupropion?
SYMPTOM MATCHING
INSOMNIA →
mirtazapine and paroxetine (not first line, but might help with need
for
sedation)?
SUICIDAL IDEATION/OVERDOSE RISK/ELDERLY →
avoid TCAs (can be fatal in overdose)
NEUROPATHIC PAIN →
duloxetine (SNRI)? (efficacy/indication for neuropathic pain)
PREGNANCY →
sertraline, fluoxetine?
AVOIDANCE OF SEXUAL DYSFUNCTION
→ strong history of prior sexual side effects →Bupropion?
1st line agents for depression
bupropion
citalopram
desvenlafaxine
duloxetine
escitalopram
fluoxetine
fluvoxamine
mirtazapine
paroxetine
sertraline
venlafaxine
vortioxetine
second line agents
levomilnacipran
meclobemide
quetiapine
trazodone
tricyclic antidepressants
vilazodone
3rd line agents for depression
phenelzine
tranylcypromine
SSRIs
-1st choice antidepressants bcuz of torelability, ease of dosing, relatively low cost.
-time to onset is 2-4 wks
-rate of response is 60-70% (comparable to tricyclic antidepressants)
SSRIs side effects
-GI tracts effects
-CNS
-Sexual dysfunction (impairment of desire)
-can increase risk of GI bleeding(in pts with additional risk)