Depression Flashcards
define a mental health disorder
*psychiatric diagnosis, mental illness
- results in significant changes in a persons thinking, emotional state and behaviour, and ability to function in social and occupational settings
define mental health problem
*poor mental health, minimal mental well-being
- broad term that includes mental health disorders and less severe mentak health symptoms that do not meet diagnostic criteria but may disrupt personal, social, and occupational functioning
history of psychiatry
divine punishment & demonic processes
bodily fluid imbalance
natural physical causes
psychological and social stress
*now = biological causes +/- psychological and social stressors
how can culture influence mental illness?
racial and ethnic minorities are less likely to seek mental health treatment than caucasians
influence treatment decisions and coping
it impacts the way people describe their symptoms
what is the purpose of the mental health services act?
assist people from serious mental illness in receiving treatment
what are the three mental health practitioners?
psychiatrist
psychologist
therapist
what is done for a clinical assessment in psychiatry?
physical exam & clinical interview
- use diagnostic statistical manual of mental disorders (DSM-5)
pros of the DSM-5
provides criteria for standardizing diagnoses
designs to produce reliable diagnosis
helps guide research in mental health
cons of DSM-5
defines illness to close to “normal” leading to overdiagnoses
largely based on expert opinion
risk of misdiagnoses
stigmatization
what is looked at during mental status exam (MSE)?
general observations
thinking
emotion
cognition
what is the difference between mood and affect?
mood is subjective - it is the inner feeling of emotion
affect is objective - its the external expression of emotional responsiveness
what is the purpose of a physical exam?
rule out medical and/or medication-induced causes
what is measurement-based care?
refers to the systematic use of measurement tools, such as validated scales, to monitor outcomes and support clinical decision-making (such as diagnosis and treatment)
what are some measurement-based scales for depression?
HAM-D
PHQ-9
BDI
what are some measurement-based scales for anxiety?
HAM-A
GAD-7
how can we remember what is measured in the PHQ-9 for depression?
SIG E CAPS
Sleep decreased
Interest decreased in activities
Guilt or worthlessness
Energy decreased
Concentration difficulties
Appetite disturbance or weight loss
Psychomotor retardation / agitation
Suicidal thoughts
what are the limitations of current psychotropic nomenclature?
outdated
does not support clinical decision-making
inconsistent with other areas of medicine
may confuse patients & exacerbate non-adherance
negatively contributes to stigma
what are the goals of the neuroscience-based nomenclature(NbN)?
- based on contemporary scientific knowledge
- help clinicians make informed choices when working out the next ‘pharmacological step’
- system of naming that does not conflict with the actual use of the medications
- be future-proof to accommodate new compounds
- help patients understand and accept a prescribed treatment for a condition
what are the 4 distinct components of stigma?
labeling someone with a condition
stereotyping people who have that condition
creating a division
discriminating against someone on the basis of their label(s)
what should you say instead of mental illness?
mental illnesses or a mental illness
what is the mental health first aid’s 5-step action plan?
A - assess for risk of suicide or harm
L - listen nonjudgmentally
G - give reassurance and information
E - encourage appropriate professional help
E - encourage self-help and other support strategies
what is the definition of major depressive disorder?
persistently and abnormally low mood, characterized by feelings of sadness, emptiness or irritability, and accompanied by other somatic or cognitive changes that significantly affect the individual’s capacity to function
T or F: depression is the leading cause of disability worldwide
False, its the 2nd leading cause
etiology of depression
complex, multifactoral (developmental, biologic, environmental)
can be genetic
what are the proposed pathophysiology theories for the cause of depression?
monoamine hypothesis
neuroplasticity hypothesis
endocrine and immune system abnormalities
structural and functional alterations
what is the monoamine hypothesis?
5HT, NE, DA
dysfunction in monoamine production (low 5HT - serotonin)
dysregulation in monoamine activity (decreased 5HT activity in presynaptic areas = upregulated autoreceptors = less 5HT in synapse)
what is the neuroplasticity hypothesis?
downstream effects -> altered cell growth and adaptation
low levels of brain-derived neurotrophic factor (BDNF) ??
what is the endocrine and immune system abnormalities theory?
increased plasma cortisol, increased peripheral cytokine concentrations
chronic stress model - involves hypothalamic-pituitary-axis(stress long term)
what is the structural and functional alterations theory?
alterations identified in brain regions involving emotional processing
- reduced volume or hyperactivity in prefrontal cortex, cingulate cortex, hippocampus, amygdala
risk factors for MDD
genetics - blood relatives
life experiences - traumatic or stressful events
personality disorders
substance use
medical comorbidities
what is DSM-5?
psychiatry diagnostic criteria
- diagnostic and statistical manual of mental disorders
what are the diagnostic criteria for MDD?
- at least 5 symptoms
- at least 1 symptom must be depressed mood or anhedonia (lack of interest)
- present nearly every day for at least a 2 week period
– symptoms cause significant distress
– episode is not attributable to direct physiological effects of a substance of another medication
– MDD is not better explained by a different mental illness
– there has never been a manic or hypomanic episode
what is considered mild MDD?
5 or 6 symptoms, minimal functional impairment
what is considered severe MDD?
nearly all symptoms, significant functional impairment or motor impairment
what are the symptoms of depression?
*depressed mood
*anhedonia
- feelings of worthlessness or guilt
- suicidal ideation, plan, or attempt
- fatigue or loss of energy
- sleep changes
- weight or appetite changes
- decreased ability to think or concentrate, or indecisiveness
- psychomotor retardation or agitation
(this is SIG E CAPS)
what are the descriptive factors for MDD?
MDD with…
- anxious distress
- mixed features
- catatonic features
- melancholic features
- atypical features
- peripartum onset
- seasonal pattern
- psychotic symptoms
what medications may be associated with MDD?
CV agents - reserpine
anticonvulsants - phenobarbital
hormonal agents - GnRH agonists
immunologic - interferon alpha
based on the PHQ-9 scale what number corresponds with the severity of depression?
<5 = no symptoms
5-9 = minimal
10-14 = moderate
15-19 = moderately severe
20-27 = severe
what are the risk factors for suicide?
I - ideation
S - substance use
P - purposelessness
A - anxiety
T - trapped
H - hopelessness
W - withdrawal
A - anger
R - recklessnes
M - mood changes
what is the prognosis for MDD?
40% recover in 3 months
60% within 6 months
80% within 12 months
15% never achieve remission
response to antidepressants
40-60% response rate
- response rate decreases with each subsequent treatment trial
what are the predictors of remission?
female sex
white race
employment
higher level of education
higher income
what is the overall goal of therapy for acute treatment of MDD?
symptom remission and restoration of premorbid functioning within 8-12 weeks
what is the overall goal for maintenance treatment of MDD?
prevent recurrence of mood episode
general goals of therapy for MDD?
minimize adverse drug effects
maximize adherence
provide education to patients and family
identify and manage risk factors for comorbid conditions
non-pharmacological treatment for MDD?
positive lifestyle changes
natural products
psychological treatment - counseling
neurostimulation
what are the pharmacological treatments?
antidepressants
adjunct drugs
what are the natural products for treatment?
st. johns wort
s-adenosyl methionine
omega-3 fatty acids
folate L-methylfolate
when is psychological treatment indicated?
for moderate to severe depression or if the patient prefers
what are the psychological treatments?
cognitive behaviuoral therapy (CBT)
behavioural activation (BA)
interpersonal psychotherapy (IPT)
mindfulness-based cognitive therapy (MBCT)
what are the neurostimulation treatments?
transcranial magnetic stimulation (TMS)
electroconvulsive therapy (ECT)
what is TMS?
used for refractory depression
magnetic fields are used to stimulate nerve cells in regions of the brain involved in mood regulation and depression
how long is TMS course?
4-6 weeks
adverse effects of TMS
headache
scalp discomfort
what is ECT?
used for severe depression, depression with psychosis or catatonic features
electrodes placed on various scalp regions
electrical charge is applied to stimulate the brain and produce a seizure while patient under general anesthetic
seizure lasts 1 minute
efficacy of ECT
80-90% effective for MDD
how many ECT treatments required?
usually 6-12
adverse effects of ECT
confusion during post-ictal period
impaired memory after procedure
headache
muscle ache
what were the conclusions from the cipriani trial?
no strong evidence to conclude that any antidepressant is superior in efficacy
new medications not better than old ones
individualize therapy
which antidepressants might have the best balance of efficacy and tolerability from meta-analyses?
sertraline
escitalopram
vortioxetine
venlafaxine
mirtazapine
what did the STAR*D trial find?
no difference in remission rates or times to remission
what are the CANMAT first-line options?
SSRI
SNRI
bupropion
mirtazapine
what is our role in MDD
provide patient centred care
- education
- empathy
ensure optimal efficacy and safety of medication use
what are the 1st line SSRIs
sertraline
escitalopram
citalopram
fluoxetine
paroxetine
what are the 1st line SNRIs
duloxetine
venlafaxine
what is the MOA of SSRIs
inhibition of presynaptic 5-HT reuptake by inhibition of the 5-HT transporter CNS neurons
- increased 5HT in synaptic cleft
what is the onset of action of SSRIs?
1st few days: decreased agitation and anxiety, improved sleep and appetite
1-3 weeks: increased activity and sex drive, improved self-care, concentration, memory, thinking and movements
2-4 weeks: relief of depressed mood
*monitor for signs of suicide within first 3 weeks
adverse effects of SSRIs
HANDS
headache
anxiety
nausea
diarrheas & other GI upset
sleep disturbances
- also anticholinergic
- sexual dysfunction
- emotional blunting/detachment
what can cause SIADH?
SSRIs
SNRIs
NSAIDs
mirtazapine
opioids
carbamazepine
pain
vomitting
inflammation
warnings for SSRI
increased risk of suicide
increased fracture risk
citalopram and escitalopram have a does-dependent risk of QTc prolongation
which SSRI is most sedating?
paroxetine
sert, and cita have mild sedation
which SSRI has a higher probability of weight gain and sweating?
paroxetine
which SSRI is the most stimulating?
fluoxetine
which SSRIs have higher rates of nausea/diarrhea?
fluvoxamine and sertraline
which SSRIs have best tolerability?
escitalopram
sertraline
what are the potent drug CYP450 drug interactions for SSRIs?
fluvoxamine - IA2 (clozapine, warfarin, methylxanthines)
fluoxetine and paroxetine - 2D6 (metoprolol, desipramine)
other drug interactions of SSRIs
NSAIDs, antiplatelets, anticoagulants
serotonergic agents
which SSRI has increased bioavailability with food?
sertraline
where are SSRIs metabolized?
liver - hepatically and only fluoxetine, citalopram and sertraline form active metabolites
what is the MOA of vortioxetine?
serotonin reuptake inhibitor
serotonin receptor agonist
serotonin receptor partial agonist
serotonin receptor antagonist
adverse effects of vortioxetine
HA
nausea
vomiting
diarrhea
sexual dysfunction
what is the MOA of SNRIs
inhibit presynaptic 5-HT and NE reuptake by inhibiting 5-HT and NE transporters in CNS neurons
at what doses will venlafaxine act like what?
binds 5-HT @ doses < 150mg/day (SSRI)
binds to NE and 5-HT @ doses >150mg/day (SNRI)
weekly inhibits dopamine @ doses >450mg/day
which SNRIs have higher overall NET inhibition and therefore higher incidence of dry mouth and constipation?
duloxetine and desvenlafaxine
which SNRI is hardest to taper off of with the most withdrawl?
venlafaxine
what is the onset of action for SNRIs?
similar to SSRIs but possibly more agitation in 1s few days
adverse effects of SNRIs
HANDS
- anticholinergic-like effects
- sexual dysfunction
- SIADH (especially venlafaxine)
- risk serotonin syndrome
- increase BP/HR and sweating
what side effect with SNRI might be less than SSRIs?
less emotional blunting than with SSRIs
PK relevance with SNRIs
dose adjustment for renal impairment
venlafaxine and duloxetine are hepatically metabolized
drug interactions of SNRIs
duloxetine - moderate inhibitor & substrate of CYP2D6
venlafaxine - weak inhibitor & substrate of CYP2D6
NSAIDs, antiplatelets, anticoagulants (caution only)
serotonergic agents
warnings with SNRIs
avoid abrupt withdrawal
duloxetine contraindicated in narrow angle glaucoma
what is the MOA of bupropion?
inhibits NE and DA transporters increasing concentrations in the synpases
- NO 5-HT effects
what is bupropion place in therapy?
useful for patients with psychomotor retardation, hypersomnia, ADHD type symptoms - its is stimulating/activating
can be used to augment SSRI or SNRI in treatment resistant cases
much less risk of sexual dysfunction
adverse effects of bupropion
agitation, insomnia, tremor and ANXIETY
sweating
reduced appetite/weight loss
GI upset
psychosis
seizures
less sexual dysfunction than SSRI and SNRI
how is bupropion metabolized?
in the liver by CYP2B6
eliminated primarily by the kidneys
- renal dosing adjustments may be needed
drug interactions for bupropion
Zyban - same drug but for tobacco cessation
concurrent MAOI therapy
potent CYP2D6 inhibitor
what is the dosing for bupropion?
usual daily dose: 100-300mg
SR formulation - OD or BID
XL formulation - OD
contraindications of bupropion
seizure disorder
eating disorders
abrupt discontinuation of alcohol or sedatives
warnings for bupropion
dependence on opioids, cocaine, stimulants
concurrent use of seizure lowering drugs
head trauma
HTN
unstable CVD/CAD
psychosis
anxiety
insomnia
overdose lethality
which treatment for MDD should you not go with if the patient has a history of overdose?
bupropion
what is the MOA of mirtazapine?
increased serotonin and NE
what is mirtazapines place in therapy?
useful as monotherapy and adjunctive treatment with SSRI or SNRI
consider in patients with insomnia, anxiety, reduced appetite
adverse affects of mirtazapine
sedation - feeling hungover the next morning
increased TGs & weight gain due to increased appetite
significantly less sexual dysfunction than SSRI/SNRI
where is mirtazapine metabolized?
hepatically
75% renally excreted
drug interactions with mirtazapine
serotonergic agents
other CNS depressants - benzodiazepines
what is the dosing for mirtazapine?
initial: 15mg PO HS
may increase q1-2 weeks up to a max of 45mg PO HS
at what dose of mirtazapine is the sedation effect typically lost?
30mg or higher
what are the second line agents for MDD?
TCAs
SNRI - levomilnacipran
MAOI - moclobemide
trazodone
atypical antipsychotic - quetiapine
vilazodone
what are the TCAs available in Canada?
tertiary amines
- amitriptyline
- clomipramine
- doxepin
- imipramine
secondary amines
- nortriptyline
- desipramine
MOA of TCAs
inhibit presynaptic 5-HT and NE reuptake by inhibiting 5-HT and NE transporters in CNS neurons
tertiary = more 5-HT activity
secondary - more NE activity, better tolerated
why are TCAs the “dirty” antidepressants?
have varying affinity for other receptors
- adrenergic
- histamine
- muscarinic
- sodium channels
where are TCAs place in therapy?
MDD with:
- insomnia
- anxiety
- chronic, non-cancer pain
- migraines/headaches
- OCD (clomipramine)
contraindications of TCAs
acute MI, heart block, CHF
severe liver impairment
cautions with TCAs
any CVD
suicidal ideation
QT prolongation
seizure history/risk
elderly
bipolar disorder
adverse effects of TCAs
sedation, anticholinergic effects, CV
- tachycardia
- QT prolongation
weight gain
tremors
sexual dysfunction
what is the lethal overdose amount for TCAs?
only ~3x max therapeutic dose
MOA of trazodone
weak inhibition of SERT and NET (doses >200mg)
adverse effects of trazodone
dizziness, sedation, headache, akathisia, myalgia, tremor
prolonged QT interval
nausea, constipation, dry mouth
sexual dysfunction (but less than SSRI/SNRI)
what kind of drug is quetiapine?
atypical antipsychotic
does MAO-A or MOA-B have more impact on serotonin and NE?
MAO-A
what is important to check before starting moclobemide (MAOI)?
*check for drug interactions
- stop serotonergic drugs 2 weeks before starting
-> Stop fluoxetine 5 weeks prior to starting
- if stopping, wait 2 weeks before starting another antidepressant
- stop at least 2 days prior to local or general anesthesia
what are the thrid line options?
irreversible MOAI
- phenelzine
- tranylcypromine
noradrenaline reuptake inhibitor
- reboxetine
where does ketamine work in the body?
NMDA receptors - inhibits sensory perception
opioid receptors (activation) - potential euphoric effects
AMPA receptors (activation) - rapid antidepressant effects
MOA of ketamine
upregulates neurotrophic signaling -> increased protein synthesis and restoration of synaptic connectivity in the prefrontal cortex
*“reset” the brain by restoring brain pathways
which type of ketamine is commercially available in Canada?
racemic ketamine - for anaesthesia
which type of ketamine is approved for depression in Canada?
s-ketamine - nasal spray
how fast does ketamine work?
within 1-2 days
adverse effects of ketamine
most common:
- dissociation
- dizziness, feeling drunk
- sedation
- increased blood pressure
nausea
Which medications are most likely to cause nausea and stomach upset?
Venlafaxine > SSRIs > bupropion > moclobemide > mirtazapine
What drugs is constipation common with?
TCAs
And paroxetine is associated with highest rates out of SSRIs
What should be done for those who develop suicidality during treatment?
Lower dose
Switch drug
Discontinue
Which drugs have the greatest risk of sexual dysfunction?
SSRIs > TCAs > SNRIs
Bupropion has lowest risk
Which drugs are lower risk for QT prolongation?
SSRIs (except cital and escital)
Bupropion
Moclobemide
How can serotonin syndrome be described?
Mental status changes
Autonomic hyperactivity
Neuromuscular abnormalities
Which drugs have worst discontinuation syndrome?
Venlafaxine and paroxetine
What is the mnemonic for symptoms of discontinuation syndrome?
FINISH
Flu-like symptoms
Insomnia
Nausea
Imbalance
Sensory disturbances
Hyperarousal
Which drug may you be able to stop without a taper and why?
Fluoxetine due to long half-life
When might we augment/combine medication?
Partial response
Faster or synergistic response
When might we switch drugs?
No response
Less pill/cost burden
Fewer adverse effects
What can be added as combo therapy for TRD?
SSRI/SNRI + mirtazapine
SSRI/SNRI + bupropion
SSRI + TCA
When is cross-tapering recommended?
Between drugs with different MOAs
What are the first line options for augmentation?
2nd gen antipsychotics
- aripiprazole*
- quetiapine *
- risperidone *
- olanzapine
What are the second line options for augmentation?
Bupropion
Mirtazapine
Lithium
Which drugs are on BEERS list?
SSRIs, SNRIs, mirtazapine
Which drugs are better choices for elderly?
Duloxetine
Bupropion
Sertraline
Are any antidepressants approved for use in <18 years?
No
Can pregnant women take antidepressants?
If they are already taking them, they should continue because the benefit often outweighs the risk of stopping
What drugs are first-line in pregnancy?
SSRIs
