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)