Exam 4 - Depression/Bipolar (Watts/Butterfield/Ott) Flashcards
3 major types of depression
reactive (60%)
MDD (major depressive disorder) (25%)
Bipolar Affective (15%)
Clinical Features of Depression:
Physiological Signs? (Main physiological signs)
Decreased sleep
Appetite Changes
Fatigue
Psychomotor dysfunctions
Clinical Features of Depression:
Physiological Signs? (“Other” physiological signs…)
Menstrual irregularities Palpitations Constipation Headaches Nonspecific Body aches
Clinical Features of Depression:
Psychological Signs?
Dysphoric mood
Worthlessness
excessive guilt
loss of interest/pleasure in all or most activities
Clinical Features of Depression:
Cognitive Signs?
Decrease concentration
suicidal ideation
Drug Induced Depression:
4 main classes of drugs that can cause this?
Anti-HTN and Cardiovascular drugs
Sedative-hypnotics
Anti-inflammatory and analgesics
Steroids
(also Miscellaneous drugs…!!)
Drug Induced Depression:
what drugs in the Antihypertensive and cardiovascular classes can cause this
reserpine methyldopa propranolol metoprolol prazosin clonidine digitalis
Drug Induced Depression:
what drugs in the sedative-hypnotics classes can cause this
alcohol
BZDs
barbituates
meprobamate
Drug Induced Depression:
what drugs in the Anti-inflammatory/Analgesic classes can cause this
indomethacin
phenylbutazone
opiates
pentazocine
Drug Induced Depression: what drugs in the steroid drug class can cause this
corticosteroids
oral contraceptives
estrogen withdrawal
Drug Induced Depression:
what Miscellaneous drug classes can cause this
anti-parkinsons
anti-neoplatics
neuroleptics
what are the 3 different hypothesises of depression
Biogenic amine
Neuroendocrine
Neurotrophic
Biogenic Amine Hypothesis of Depression:
overall idea behind it?
reserpine causes depression by depleting NE and HT from vesicles
Biogenic Amine Hypothesis of Depression:
________ causes depression by depleting ____ and _____
reserpine; NE; 5HT
Biogenic Amine Hypothesis of Depression:
Agents that increase _______ and ______ are effective for treating depression
5HT; NE
Biogenic Amine Hypothesis of Depression:
Genetic polymorphisms are seen in ________
SERT promoter
Biogenic Amine Hypothesis of Depression:
Alterations in that receptors are seen?
5HT1A or 5HT2C
and
alpha 2 receptors (aka NE receptors!)
Neuroendocrine Hypothesis of Depression:
overall idea of it?
changes in HPA Axis happen which leads to desensitized feedback response and leads to increased CRF
Neuroendocrine Hypothesis of Depression:
Changes are seen in the __________
HPA Axis
(hypothalamus-pituitary-adrenal) axis
Neuroendocrine Hypothesis of Depression:
stress causes hypothalamus to release _____
CRF
Neuroendocrine Hypothesis of Depression:
CRF will promote release of _____ from ____
ACTH; from pituitary
Neuroendocrine Hypothesis of Depression:
ACTH promotes release of ______ from _____
cortisol; from adrenal
Neuroendocrine Hypothesis of Depression:
Almost all patients with depression have overactivity of ______ and elevated ______
HPA; CRF
Neuroendocrine Hypothesis of Depression:
Overactivity of HPA may ___________ response in hypothalamus and pituitary
desensitize feedback
Neuroendocrine Hypothesis of Depression:
Overactivity of HPA may desensitize feedback response in ____________
hypothalamus and pituitary
Neuroendocrine Hypothesis of Depression:
Elevated CRF causes what things?
insomnia
anxiety
decrease appetite and libido
Neuroendocrine Hypothesis of Depression:
_______ CRF causes insomnia, anxiety, and decrease appetite and libido
elevated
Neuroendocrine Hypothesis of Depression:
antidepressants and ECT (electroconvulsive therapy) will (increase or decrease) CRF levels
decrease!!
Neurotrophic Hypothesis of Depression:
overall point?
BDNF can have antidepressant activity;
BDNF = brain derived neurotrophic activity
Neurotrophic Hypothesis of Depression:
BDNF stands for what?
brain derived neurotrohpic factor?
Neurotrophic Hypothesis of Depression:
BDNF is critical in what 3 things?
neural plasticity
resilience
neurogenesis
Neurotrophic Hypothesis of Depression:
Stress and pain (increase or decrease) BDNF in animals
decrease
Neurotrophic Hypothesis of Depression:
Depressed patients have reduced _____ levels
BDNF
Neurotrophic Hypothesis of Depression:
Antidepressants increase ______ levels and my increase _______
increase BDNF levels; increase hippocampal volume
Integrating Hypothesis of Depression:
______ and _______ regulate BDNF levels
HPA and steroid abnormalities
Integrating Hypothesis of Depression:
___________ receptors are activated by cortisol during stress (which ______ BDNF)
hippocampal gluccorticoid;
decrease BDNF
Integrating Hypothesis of Depression:
Chronic activation of monoamine receptors increase ________
BDNF signaling
Integrating Hypothesis of Depression:
chronic activation of of monoamine receptors leads to down regulation of _______
HPA axis
Main Classes of Antidepressants?
MAOIs TCAs SSRIs SNRIs 5-HT2 antagonists
why does antidepressant therapy take 2 - 3 weeks?
neuroadaptive responses
MOA of MAOIs?
inhibit break down of NE and 5HT = more NE and 5HT is released from vesicles into synapses
what drugs are are non-selective MAO inhibitors
Phenelzine
Tranylcypromine
what drug is MAO B selective
Selegiline
what drug is MAO A selective
Moclobemide
are MAOIs reversible or irreversible?
irreversible
(thus when switching agents must have some time from stopping MAOI and starting another drug because it may cause hella side effects)
Severe Side Effects of MAO Inhibitors
HA drowsiness dry mouth weight gain orthostatic hypotension sexual dysfunction
MAO-I has interactions with what Rx drugs?
TCAs
SSRIs
L-DOPA
MAOIs should be avoided with that foods?
tyramine rich (aka cheeses, sour cream, sausage, red wine/beer/ale, miso soup, avocados, bananas and a million other foods...)
MAOIs have interactions with what OTC meds?
Cold preparations
Diet pills
MAOIs can lead to a _______ crisis
hypertensive
what are the two subgroups of TCAs
tertiary amine
and
secondary amine
indications for TCAs?
depression
panic disorder
chronic pain
enuresis
TCAs:
pts are more likely to commit self harm or suicide ________ into treatment
2 weeks
TCAs:
Toxicity risk — extremely _________ pts more likely to be suicidal
dangerous/depressed
Tertiary Amines - TCAs:
they inhibit both _____ and ____ reuptake via ___ and ____
NE and 5HT;
via NET and SERT
Tertiary Amines - TCAs:
major side effects?
sedation
autonomic side effects
weight gain
Tertiary Amines - TCAs:
also act as antagonists to what?
they are antihistamines
anitmuscarinic
antiadrenergic
what are the tertiary amine TCAs?
Imipramine Amitriptyline Trimipramine Clomipramine Doxepin
Secondary Amines - TCAs:
inhibit _______ but not _____ like tertiary amine TCAs do
inhibit NET
not SERT
(*remember secondary has an N in it…)
what are the secondary amine TCAs?
desipramine
nortriptyline
protriptyline
maprolitine
TCAs:
secondary or tertiary amines have worst side effect profiles?
tertiary amines
is it TCA (tertiary or secondary), SSRI, or SNRI?
imipramine
tertiary
is it TCA (tertiary or secondary), SSRI, or SNRI?
Desipramine
secondary
is it TCA (tertiary or secondary), SSRI, or SNRI?
Amitriptyline
tertiary
is it TCA (tertiary or secondary), SSRI, or SNRI?
doxepin
tertiary
is it TCA (tertiary or secondary), SSRI, or SNRI?
nortriptyline
secondary
is it TCA (tertiary or secondary), SSRI, or SNRI?
maprotiline
secondary
is it TCA (tertiary or secondary), SSRI, or SNRI?
trimipramine
tertiary
is it TCA (tertiary or secondary), SSRI, or SNRI?
clomipramine
tertiary
is it TCA (tertiary or secondary), SSRI, or SNRI?
protriptyline
secondary
is it TCA (tertiary or secondary), SSRI, or SNRI?
fluoxeine
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
Fluvoxamine
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
Venlafaxine
SNRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
Duloxetine
SNRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
desvenlafaxine
SNRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
paroxetine
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
sertraline
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
citalopram
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
escitalopram
SSRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
Milnacipran
SNRI
is it TCA (tertiary or secondary), SSRI, or SNRI?
Levomilnacipran
SNRI
what drugs are SSRIs
fluoxetine fluvoxamine paroxetine sertraline citalopram escitalopram
what drugs are SNRIs
venlafaxine desvenlafaxine duloxetine milnacipran levomilnacipran
what are the side effects of SSRIs
N/V HA sexual dysfunction anxiety!! insomnia!!! (NOT sedation) tremor
SSRI discontinuation syndrome — symptoms?
"brain zap" dizziness sweating nausea insomnia tremor confusion vertigo
what drugs are NSRI
reboxetine
atomoxetine
what drugs may be used as a rapidly acting antidepressants
NMDA receptor antagonists
like ketamine, scopolamine
Non-Pharm options (per watts)
electroconvulsive therapy
psychotherapy
hospitalization
MOA of Lithium?
depletes PIP2 and assoc. signaling (IP3 and PKC)
modules GSK3 (ultimately a;ters to gene transcription)
MOA of Valproate
increase GABAergic tone
Block Na+ channels and Ca2+ channels
and inhibit histone deacetylase
MOA of CBZ
inhibit Na+ channels
MOA of lamotrigine
inhibit Na+ and Ca2+
DSM - 5 Diagnostic Criteria for Depression:
____ or more of the symptoms listed are present during the same _____ week period and is a change from baseline
5 symptoms;
greater than 2 week period
DSM - 5 Diagnostic Criteria for Depression:
need at least one of two symptoms (as part of the 5 total)
what are the 2 symptoms
depressed mood
or
loss of interest or pleasure
DSM - 5 Diagnostic Criteria for Depression:
what are the other symptoms that can be part of the diagnosis
SIGECAP! S-suicidal ideation I-insmonia/hypersomnia G-guilt/worthlessness E-Energy loss/fatigue C-Concentration difficulties A-Appetite changes P-psychomotor agitation/retardation
Risk factors for MDD: male or female? age? marital status? race? economic status? employment? co-morbid \_\_\_\_\_\_\_ and \_\_\_\_\_ Physical \_\_\_\_\_\_\_\_\_ lack of \_\_\_\_\_\_ \_\_\_\_\_\_\_\_ experiences prior \_\_\_\_\_\_\_\_
female middle age widowed/separated/divorced/single white race low econom. status unemployed co-morbid: medical disorder and substance use disorder physical DISABILITY lack of SOCIAL SUPPORT stressful events/adverse childhood experiences prior suicidal attemps
Depression Recurrence Rates:
if 1 episode: _____ %
if 2 episodes: _____%
if 3 episodes: ____%
50 - 60
70
90
what screening scales are self administered for depression
PHQ-9
QIDS-SR-16
MDQ
what screening scales are clinician rated for depression
HAM-D
QIDS-C
CGI
what screening scale is commonly used for clinical trial effiacy for antidepressants
HAM-D
Boxed Warning for Antidepressants:
increase risk of suicidal thought behaviors in those aged < 24 y.o
No increase in suicides seen tho
how to manage/”deal with” the boxed warning that comes with antidepressants
still give it to them (even pts under 24)
just closely monitor pts for clinical worsening/suicidal ideation, or unusual changes in behavior esp. for first 3 MONTHS of therapy or any dose changes
Clinical Pearls for Citalopram:
ADE of _______ seen when dose > 40 mg/day
and
CYP_______?
QT prolongation
2C19 (substrate)
Clinical Pearls for Escitalopram
CYP______?
and is the ______ of citalopram
2C19 and 3A4!
s isomer
Clinical Pearls for fluoxetine:
long or short half life?
CYP?
ADEs?
long half life
2D6 and 3A4
ADEs: insomnia, initial weight loss, fatigue syndrome
Clinical Pearls for Fluvoxamine:
FDA approved for _______
CYP____?
OCD tx
1A2
Clinical Pearls for Paroxetine: Must \_\_\_\_\_\_\_\_ because of \_\_\_\_\_\_ effects CYP\_\_\_\_\_? ADEs: Pregnancy Category \_\_\_\_: leads to?
must TAPER; b/c of ANTICHOLINERGIC effects
2D6
ADE: weight gain/sedation/anticholinergic
Category D; SEPTAL WALL DEFECTS
Clinical Pearls for Sertraline
CYP_____?
More ____ at higher doses
2D6 (mainly but also all the usual thing)
GI upset
which SSRI notably causes weight gain
paroxetine
which SSRI notably causes weight loss
fluoxetine
Overall SSRI ADEs?
variable sedation increased BLEEDING risk GI upset anxiety/agitation sexual dysfunction hyponatremia decreased bone mineral density akathisia (weight gain or weight loss)
SSRIs:
take about _______ for onset of action
and
________ until full dose response is observed
1 - 2 weeks (onset)
4 - 6 weeks (full dose response)
Clinical Pearls for Desvenlafaxine: \_\_\_\_\_\_\_\_\_ of venlafaxine dose limiting side effect of \_\_\_\_\_\_\_\_ CYP\_\_\_\_\_\_? \_\_\_\_\_ dosing adjustments
active metabolite of venlafaxine
nausea
no CYP!
renal dosing
Clinical Pearls for Duloxetine:
CYP_______
how to help with nausea?
FDA warning for _______
2D6
slow titration or divided dosing to help w/ nausea
warning for HEPATOXICITY *gotta check LFTS at baseline and q 6 mos)
Clinical Pearls for Levomilnacipran:
CYP_______
MUST adjust for what things?
Rare SEs?
3A4
renal dosing OR major CYP3A4 inhibitor
SE: seizures or glaucoma
brand for Levomilnacipran
Fetzima
brand for milnacipran
Savella
brand for desvenlafaxine
pristiq
Clinical Pearls for Milnacipran
indicated for _________
____ dosing adjustments
fibromyalgia
renal dosing
Clinical Pearls for Venlafaxine:
CYP________
Dose must be > ______ mg/day to have _____ effect
2D6 and 3A4
150 mg; NE effects
SNRIs can be helpful for what other things? (not depression…)
pain syndrome
musculoskeletal pain
fibromyalgia
neuropathic pain
what is the one ADE that is different for SNRIs compared to SSRIs
blood pressure elevation seen in SNRI (bc NE effect!!)
Clinical Pearls for Amitriptyline:
Used at _____ doses for ______ pain
lower; neuropathic
Clinical Pearls for Desipramine:
just one pearl for this drug
not commonly used for depression..
Clinical Pearls for Doxepin:
CYP_____
Commonly used for ______
2D6
insomnia
Clinical Pearls for Imipramine:
most often used for children with ______ or ______ at ______ doses
ADHD; noctural enuresis
lower doses
Clinical Pearls for Nortriptyline:
used in __________
smoking cessation
what TCA is used for smoking cessation
notriptyline
which TCA is used for ADHD
imipramine
which TCA is used for neuropathic pain
amitriptyline (also nortriptyline)
which TCA is the only one with a notable CYP interaction and what is the interaction
doxepin
CYP2D6
which SNRIs need renal adjustmnet
desvenlafaxine
milnacipran
levomilnacipran
which SNRI is indicated for fibromyalgia
milnacipran
which SNRI has a FDA warning for hepatoxicity
duloxetine
TCAs can be fatal in overdose due to ________
cardiac arrhythmias
Clinical Pearls for all MAOIs?
must have 2 week washout period before switching antidepressants
all drugs need tyramine diet except selegiline (6mg/24 hr)
Caution with MAOIs due to _______ and _______
hypertensive crisis
and
serotonin syndrome
MAOIs contraindications? (8 in total)
Pheochromocytoma Hepatic or renal dysfunction Excessive caffeine use Cerebrovascular disease Concomitant sympathomimetics (amphetamines and cocaine..) Cardiovascular disease Elective surgery SSRI use (gotta d/c 2 -5 weeks before starting MAOI)
(PHECCCES)
why is tyramine a note of concern with MAOIs
tyramine is degraded by MAO;
MAOIs wont break down tyramine, leads to hypertensive crisis
Any drug that increases _________ in the brain are basically a drug interaction for MAOIs
increase NEUROTRANSMITTERS
MAOI Patch has what drug in it?
Selegiline
Selegine Patch:
monotherapy or adjunct therapy?
monotherapy!
ADEs for selegiline patch?
hypotension
dry mouth insomina
headache
Gi effects
what are the “novel agents” for depression
bupropion mirtazapine trazodone Vilazodone (Viibryd) Vortioxetine (Trintellix)
what is the brand for vilazodone
Viibyrd
what is the brand for vortioxetine
Trintellix
Bupropion:
____ and ___ reuptake inhibitor
DA and NE
Bupropion:
it is stimulating and thus can cause ______ and _____
insomnia
appetite suppresion
Bupropion:
CI with what 2 things?
seizures
eating disorders
Bupropion:
if using SR formulation; do not give 2nd dose no later than ______
4pm
Bupropion:
major CYP stuff?
2B6 Substrate
2D6 inhibitor
Bupropion:
T or F: it can not be used with SSRIs or SNRIs
False!
it can be used with them
Mirtazapine:
increased _____ and _____ occur with doses < ____ mg/day
sedation; appetite
15 mg/day
Mirtazapine:
warnings for ______ and ______
agranulocytosis
and
increased cholesterol
Mirtazapine:
T or F: it can not be used with SSRIs or SNRIs
False!
it can be used with them
Trazodone:
risk of ______ - medical emergency
priapism
Vilazodone:
should it be taken with or without food?
WITH FOOD!!
better absorption AND hella nausea is possible
Vilazodone:
CYP interaction?
3A4
half the max dose if strong 3A4 inhibitor
Vortioxetine:
CYP interaction?
2D6:
half the max dose if strong 2D6 inhibitor
Antidepressant withdrawal syndrome:
occurs due to abrupt cessation of the antidepressant - and it is common in all depressants except _______
fluoxetine (bc it has a long half/can handle its own taper)
Want to avoid cholinergic rebound - therefore HAVE to taper ______ and _____ (aka the anticholinergic antidepressants)
paroxetine; TCAs
Symptoms of Antidepressant withdrawal syndrome?
agitation
irritability
GI disturbances
(similar to depression…)
what drugs are Augmentation agents for depression
Lithium
T3
atypical antipsychotics
buspirone