Depression Flashcards
DSM-5 criteria for MDD
5 symptoms present during the same 2 week period
depressed mood or decreased interest + 4 symptoms from DSIGECAPS
DSIGECAPS
depressed mood
sleep
interest
guilt
energy
concentration
appetite
psychomotor
suicide
onset of MDD
most commonly late 20s but can develop at any age
duration of MDD
median time to recovery is 20 weeks with adequate treatment
__% of patients with a single episode with recover without recurrence
50%
what defines a RESPONSE to treatment
> 50% reduction in symptom severity
what defines REMISSION
absence of depressive symptoms (or only 1-2 mild symptoms) for >2 months
goal of acute phase
remission
select initial agent based on patient factors, optimize regiment
goal of continuation phase
prevent RELAPSE
goal of maintenance phae
prevent RECURRENCE
monoamine hypothesis
depressive symptoms related to deficiencies in 5HT, NE, DA
dysregulation hypothesis
depression results from dysregulation of neurotransmitters that leads to alterations in pre & post receptors
neuroendocrine hypothesis
dysregulation of thyroid & HPA axis results in depression
SSRI mechanism
inhibit reuptake of 5HT in the presynaptic neuron of CNS–> leading to increased serotonin in synaptic cleft
SSRI place in therapy
first line for MDD: well tolerated, low toxicity
SSRI (general) dosing
daily
SSRI drugs
citalopram
escitalopram
sertraline
paroxetine
fluoxetine
fluvoxamine
vortioxetine
COMMON ssri side effects
n/v
headache
sleep changes
increased anxiety/agitation or sedation
sexual dysfunction
SERIOUS ssri side effects
hyponatremia
increased bleeding/bruising
serotonin syndrome
most ACTIVATING ssri
fluoxetine
most SEDATING ssri
paroxetine
what is the “dirty ssri” and why
paroxetine: it is anticholinergic and antihistaminic, more sexual dysfunction, most weight gain
which ssri causes the most diarrhea and why
sertraline: it can affect serotonin in the gut
which ssris have most QT prolongation risk
citalopram
escitalopram
SNRI mechanism
inhibits the reuptake of serotonin and norepinephrine presynaptically
SNRI place in therapy
first/second line for MDD: low toxicity, addition mechanism with NE
what are the SNRIs
venlafaxine
duloxetine
desvenlafaxine
levomilnacipran
what are common side effects of SNRIs
same as SSRIs PLUS dose-dependent BP elevation, constipation
what are serious side effects of SNRIs
hyponatremia, increased bleeding/bruising, serotonin syndrome
SARIs
trazodone, nefazodone
SARI mechanism
5HT2A and 5HT2C receptor antagonist (post-synaptic)
inhibits serotonin reuptake
SARI place in therapy
not usually first or second line because too sedating
SARI adverse effects
sedation, dizziness, orthostatic hypotension, priapism
trazodone is used for
most commonly for insomnia rather than MDD
nefazodone boxed warning
liver failure
not first line due to this toxicity
NDRI mechanism
inhibits reuptake of norepi and dopamine, no serotonin activity
NDRI place in therapy
first or second line treatment of MDD
NDRI drug
bupropion
NDRI side effects
activation (insomnia, agitation, tremor), weight loss, headache, n/v, constipation
benefits of NDRI
fatigue, poor concentration, smoking cessation
NDRI contraindications
bulimia, anorexia, seizure disorders
appetite suppression & lowers seizure threshold
what does it mean that NDRI is activating
may exacerbate anxiety, caution in patients with psychotic features
NDRI can be used for?
ssri-induced sexual dysfunction, smoking cessation
NaSSa
mirtazapine
NaSSa mechanism
primary: alpha2 antag
secondary: 5HT2, 5HT2C, 5HT3 antagonist, antihistamine
mirtazapine place in therapy
considered second line
mirtazapine side effects
weight gain and sedation worse at lower doses
less sexual dysfunction
serotonin modulator
vilazodone
vilazodone mechanism
serotonin reuptake inhibitor, 5HT1A partial agonist
dosing vilazodone
daily at bedtime with food to inc bioavail
which drug has the lowest incidence of sexual dysfunction
vilazodone
TCA mechanism
presynaptic inhibition of NE and 5HT reuptake: increase them in synaptic cleft
varying affinity for H1, alpha, muscarinic
TCA place in therapy
effective but third/fourth line due to toxicity in overdose & overall tolerability
which TCAs are tertiary amines
amitriptyline
clomipramine
doxep8in
imipramine
which TCAs are secondary amines
amoxapine
desipramine
nortriptyline
what does tertiary amine mean
more anticholinergic, alphalytic, antihistaminergic
what does secondary amine mean
more NE reuptake inhibition
common TCA side effects
anticholinergic
antihistaminergic
orthostasis
photosensitivity
serious TCA side effects
cardiotoxicity: QT prolongation, risk of MI
decrease seizure threshold
what is the most anticholinergic and alphalytic TCA
amitriptyline
what is amitriptyline used for
chronic pain, migraine
what is the most serotonergic TCA
clomipramine
what is clomipramine used for
OCD
what is the most noradrenergic/lowest anticholinergic TCA
desipramine
what is the most antihistaminic TCA
doxepin
what is imipramine used for
GAD, panic disorder with agoraphobia
what is the best tolerated TCA
nortriptyline
MAOI mechanism
inhibition of monoamine oxidase enzymes (MAO-A & MAO-B) resulting in increased concentrations of NE, 5HT, DA in synapse
common MAOI side effects
hypotension, dizzy, urinary retention, constipation, xerostomia
serious MAOI side effects
hypertensive crisis (drug-food interaction)
serotonin syndrome (drug-drug interaction)
definition of hypertensive crisis
diastolic BP> 120 mmHg
symptoms of hypertensive crisis
occipital headache, palpitations, neck stiffness, n/v, dilated pupils/photophobia, tachy/bradycardia, chest pain
MAOIs require dietary modifications to prevent food-drug interaction with _____
tyramine
foods to avoid with MAOIs
dried, aged, smoked, fermented, spoiled meat/fish
broad bean pods
aged cheese
tap & non-pasteurized beer
marmite, sauerkraut
soy products/tofu
foods allowed with MAOIs
fresh/processed meat
veggies
processed & cottage cheese, ricotta, yogurt
canned/bottled beers
brewer’s and baker’s yeast
treatment of hypertensive crisis with MAOIs from tyramine
phentolamine
nifedipine, chlorpromazine
drug-drug interactions with MAOIs
decongestants (eg sudafed)
stimulants (amphetamine, coke)
antidepressants w/ NRI (TCA, NRI, SNRI, NDRI)
appetite suppressants (phentermine)
selegiline pearls
selective for MAO-B
no need for dietary restriction w/ patch
but drug-drug interactions still a concern
phenelzine pearls
weight gain, hepatotoxicity
tranylcypromine pearls
similar to amphetamine structurally (stimulating)
insomnia
transient hypertension
serotonin syndrome
agitation, tachycardia, diarrhea, diaphoresis, clonus, tremor, hyperreflexia
DDIs causing serotonin syndrome
antidepressants
other TCA-like drugs
antibiotics (linezolid)
appetite suppressants (sibutramine)
opioids
prevention of serotonin syndrome with MAOIs
allow for a 2 week washout period
(5 week after fluoxetine)
boxed warning on all antidepressants
suicidality in children/antidepressants up to 24 years old
discontinuation syndrome
flu-like, paresthesia
drug with most severe discontinuation syndrome
venlafaxine
onset of discontinuation syndrome
1-2 days after d/c
MDD treatment in pregnancy?
avoid paroxetine
postpartum depression treatment?
SSRIs are first line
MDD treatment in peds?
SSRIs: fluoxetine, escitalopram, citalopram, sertraline
MDD treatment in elderly?
start low and go slow
may manifest as cognition changes
first line in MDD treatment algorithm
psychotherapy, SSRI, SNRI, mirtazapine, bupropion
improvements seen in week 1
decrease anxiety
increase sleep, appetite, energy
improvements seen in week 2
increase activity, self care, memory, concentration
improvements seen in week 3
decreased depression, hopelessness
when is full response seen
4-6 weeks
what is an adequate trial
6 weeks
define treatment resistant depression
failure of at least 2 treatment attempts of adequate dose and duration
options for treatment resistant depression
SGA
lithium
buspirone
stimulants
esketamine
