depression

Question 1

types of depression

• ___ (60%)
• major depressive disorder (25%)
• bipolar affective (15%)

common mental illness of general population
- 10%, underdiagnosed, untreated, suicidal

Answer 1

• reactive

Question 2

clinical features

physiological - decreased ___, appetite changes, fatigue, psychomotor dysfunctions
- ___ irregularities, palpitations, constipations headaches/non-specific body aches

psychological - dysphoric mood, worthlessness, excessive guilt, loss of interest/pleasure in all or most activities

cognitive - decreased ___ , suicidal ideation

diagnosis: not due to drugs, medical conditions, or bereavement

Answer 2

• sleep, menstrual
• concentration

Question 3

drug induced depression

Antihypertensive and Cardiovascular:
- ___ , methyldopa, propranolol, metoprolol, prazosin, clonidine, digitalis

Sedative-Hypotics
- ___ , benzodiazepines, barbiturates, meprobamate

Anti-inflammatory and analgesics
- indomethacin, phenylbutazone, ___ , pentazocine

steroids
- ___ , oral contraceptives, ___ withdrawal

MSC
- antiparkinson, anti-neoplastic, neuroleptics

Answer 3

• reserpine
• alcohol
• opiates
• corticosteroids, estrogen

Question 4

biogenic amine hypoothesis of depression

• reserpine causes depression by depleting ___ and ___ from vesicles
• genetic polymorphisms in ___ promoter
• alterations in 5HT1A/2C and a2 receptors

Answer 4

NE, 5HT
SERT

Question 5

neuroendocrine hypothesis of depression

changes in ___ axis
1) stress causes hypothalamus to release ___
2) promotes the release of ___ from pituitary
3) promotes release of ___ from adrenal

overactivity and elevated ___ found in almost all depressed patients
- may ___ feedback response in hypothalamus and pituitary
- causes insomnia, anxiety, and decreased appetite and libido
- antidepressants and ECT reduce these levels

Answer 5

• HPA
• CRF
• ACTH
• cortisol
• CRF
• desensitize

Question 6

CRF1 receptor
- arousal
- ___ like behavior
- disruption of ___ behaviours
- disruption of ___

CRF2
- slow adaptive recovery
- ___ suppression

Answer 6

• anxiety
• sexual
• sleep
• appetite

Question 7

Neurotrophic hypothesis of depression

• brain derived neurotrophic factor (BDNF) - critical in neural ___ , resilience, neurogenesis
• stress and pain ___ BDNF levels in animals
• decreases volume of ___ (memory and regulation of HPA)
• BDNF acts as an ___ in animals; antidepressants increase BDNF and can increase hippocampal ___

conflicting animal studies with opposing evidence tho

Answer 7

• plasticity
• decrease
• hippocampus
• antidepressant
• volume

Question 8

integration of hypotheses of depression

• HPA and ___ abnormalities regulate BDNF levels
• hippocampal glucocorticoid receptors are activated by ___ during stress (decreasing BDNF)
• chronic activation of ___ receptors increases BDNF signaling ( >2 weeks), leads to ___ of HPA axis

Answer 8

• steroid
• cortisol
• monoamine, downregulation

Question 9

Why does therapy take 2-3 weeks?

antidepressants cause the amount of neurotransmitter in the intrasynaptic space to ___

is the delay in clinical effect due to:
- ___ of presynaptic receptors?
- presynaptic and postsynaptic ___?

no one really knows

Answer 9

increase
activation
adaptation

Question 10

MOA: MAO-i

• ___ and ___ are degraded by monoamine oxidase
• by inhibiting, we increase the amount transmitted by vesicles into the synapse

Answer 10

• NE, 5HT

Question 11

MAO-i

non-selective:
- ___ (Nardil)
- ___ (Parnate)

MAO-B selective:
- ___ (Eldepryl/Ensam)
- ___ (Xadago)

MAO-A selective:
- ____ (Manerix)

Answer 11

• phenelzine
• tranylcypromine
• selegiline
• safinamide
• moclobemide

Question 12

MAO-i Structures

Answer 12

phenelzine

similar to amphetamine

Question 13

MAO-i Structures

Answer 13

tranylcypromine

Question 14

MAO-i

Severe SE:
- headache, drowsiness, drymouth, weight gain, orthostatic hypotension, sexual dysfunction

Hypertensive crisis: avoid certain foods (containing ___ ) and drugs

Interactions with OTCs: colds preparations, diet pills, and ___

Interactions with Rx: ___ , ___ , and ___

Answer 14

• tyramine
• St. John’s Wort
• TCAs, SSRIs, L-DOPA

Question 15

Tricyclic antidepressants

indications: depression, panic disorder, chronic pain, and enuresis

overdose/toxicity: extremely dangerous, depressed patients have an ___ in suicidality
- patients are more likely to commit self-harm or suicide ___ weeks into treatment

Answer 15

increase
- 2

Question 16

tertiary amines

inhibit both NE and 5HT ___ via NET and SERT

also act as receptor antagonists
- antihistamine (H1)
- antimuscarinic
- antiadrenergic (a1)

major side effects: these agents cause the most ___ , autonomic side effects, and weight gain

Other Side Effects: conduction disturbances of ___

Answer 16

reuptake
- sedation
- heart

Question 17

tertiary amines

___ (Tofranil)
- metabolized to desipramine
- enuresis and ADHD

___ (Elavil)
- metabolized to nortiptyline

Answer 17

imipramine
amitriptyline

Question 18

tertiary amines

trimipramine (Surmontil)

clomipramine (Anafranil)
- used for ___

____ (Adapin, Sinequan)

Answer 18

OCD
doxepin

clomipramine - causes orgasm when yawning

Question 19

secondary amines

Drug
- ___ (Norpramin)
- ___ (Pamelor)
- ___ (Vivactil)
- ___ (Lumdiomil) - ___ inhibitor (tetracycline reduced side effects)

SE: ___ sedation, ___ anticholinergic, ___ autonomic, ___ weight gain, ___ cardiovascular than tertiary amines

in general, side effects of all TCAs
- anticholinergic, ___ (elderly), neurological, weight ___
- ___ suicidality

Answer 19

• desipramine
• nortriptyline
• protriptyline
• maprotiline, NET
• less, less, less, less, less
• CV, gain
• increased

Question 20

SSRI

Drug
- ___ (Prozac): little autonomic SE, no ___
- ___ (Luvox)
- ___ (Paxil)
- ___ (Zoloft)
- ___ (Celexa)
- ___ (Lexapro): isomer of citalopram

Answer 20

• fluoxetine, sedation
• fluvoxamine
• paroxetine
• sertraline
• citalopram
• escitalopram

Question 21

SSRI

T or F: there is a structural pattern to SSRIs

Answer 21

False: all over the place

Question 22

SSRI

Uses: depression, alcoholism, OCD, enuresis, PTSD, eating disorders, social phobias, panic anxiety, PMDD, GAD

SE: N/V, headache, sexual dysfunction, ___ , insomnia, tremor

D/C syndrome: brain ___ , dizziness, ___ , nausea, insomnia, tremor, confusion, vertigo

Serotonin Syndrome: when given with ___ , TCAs, metoclopramide, triptans, ___ , St. John’s wort
- symptoms: hyperthermia, muscle rigidity, restlessness, myoclonus, hyperreflexia, sweating, shivering, seizures, and coma
- treatment: d/c of medication and management of symptoms, administration of serotonin antagonists ( ___ or methysergide); ___ to control myoclonus

Answer 22

• anxiety
• zaps, sweating
• MAOIs, tramadol
• cyproheptadine, benzodiazepines

Question 23

SSRI + 5HT1A partial agonists

___ (Viibryd)
- IC50 for SERT and 5HT1A ___ (0.5 nM)
- 60-70% intrinsic activity
- reduced ___ SE vs pure SSRIs
- similar 5HT1A actions to: aripiprazole and buspirone

___ (Trintellex)
- SERT (2 nM), 5HT1A partial agonist (15 nM) (70-80% intrinsic activity), and 5HT3 (4 nM)

Answer 23

vilazodone
- similar
- sexual

vortioxetine

Question 24

Tetracyclic and Unicyclic

___ (Ludiomil)
- ___ inhibitor

___ (Ascendin)
- ___ inhibitor
- ___ antagonists

Answer 24

maprotiline
- NET

amoxapine
- NET
- D2

Question 25

# Tetracyclic and Unicyclic ___ (Remeron) - a2, __ , 5HT__ , 5HT __ antagonists

Answer 25

mirtazapine - H1 - 5HT2 , 5HT3

Question 26

# Tetracyclic and Unicyclic ___ (Wellbutrin) - ___ inhibitor - ___ and ___ inhibitor - also treat GAD - " ___ " for smoking cessation

Answer 26

bupropion - DAT - NET, SERT - Zyban

Question 27

# 5-HT2 antagonists/SERT inhibitors ___ (Dyserel) - ___ antagonist - weak ___ inhibitor - off label ___ (a1, H1, with 5HT2)

Answer 27

trazodone - 5HT 2A - SERT - hypnotic | Have to take huge doses as antidepressant, super sedating

Question 28

# SNRIs ___ (Effexor) - ___ and __ inhibitor - treats GAD and panic disorder - might be useful for diabetic ___ and ___ prophylaxis (?)

Answer 28

venlafaxine - NET, SERT - neuropathy, migraine

Question 29

# SNRIs ___ (Pristiq) - ___ and ___ inhibitor - useful for vasomotor symptoms associated with ___ (?)

Answer 29

desvenlafaxine - NET, SERT - menopause

Question 30

# SNRIs ___ (Cymbalta) - ___ and ___ inhibitor - treats GAD - treats peripheral ___

Answer 30

duloxetine - NET, SERT - neuropathy

Question 31

# SNRIs ___ (Ixel) - ___ and ___ inhibitor - approved for ___

Answer 31

milnacipran - NET, SERT - fibromyalgia

Question 32

# SNRIs ___ (Fetzima) - active enantiomer or ___ - ___ and ___ inhibitor

Answer 32

levomilnacipran - milnacipran - NET, SERT

Question 33

# NSRIs ___ (Vestra, Edronax) - possible less side effects than ___ - not available in US

Answer 33

reboxetine - Prozac

Question 34

# NSRIs ___ (Straterra) - originally intended to be an antidepressant (not approved) - used for ___

Answer 34

atomoxetine - ADHD

Question 35

# Selectivity Profiles ___ number = more selective - amitriptyline more selective for ___ - nortriptyline more selective for ___ - escitalopram is super selective for ___

Answer 35

smaller - 5HT - NE - 5HT

Question 36

# SNDRIs "triple blockers" / "triple reuptake inhibitors" - ___ and ___ - early research as Parkinson's therapies - ___ currently being researched as an appetite suppressant - new drugs coming out for treatment of depression

Answer 36

- tesofensine, brasofensine - tesofensine

Question 37

# rapidly acting antidepressants: NDMA antagonists - ___ subanesthetic doses - ___ (muscarinic and NMDA antagonists) - Lanicemine "low trapping" - GLYX-13 partial NMDA antagonists

Answer 37

- ketamine - scopolamine

Question 38

# clinical used NMDA antagonists ___ - subanesthetic doses ___ (Spravato) - in conjunction with oral antidepressant - CNS effects: ___ , drug interactions - intranasal, phased dosing - available only through ___ program

Answer 38

ketamine esketamine - depression - REMS

Question 39

# Postpartum Depression PPD occurs within 4 weeks and can last for over a year. 10-15% of moms SSRIs ( ___ and ___ ) and ___ **___ (Zulresso) - new MOA involving ___ receptors**

Answer 39

- fluoxetine, paroxetine, venlafaxine - brexanolone, GABA A

Question 40

# Brexanolone (Zulresso) - ___ levels increase during pregnancy - ___ receptors desensitize (?) - levels return to normal postpartum - brexanolone resensitizes receptors - ___ program - ___ hr infusion ($20,000-30,000)

Answer 40

- allopregnanolone - GABA-A - REMS - 60 hr

Question 41

# new agents in development psychedelics: MDMA, psilocybin, LSD 5HT ___ receptor antagonists metabotropic ___ receptor agonosts reversible inhibitors of ___ A (RIMAs) - moclobemide and brofaromine - are as efective as ___ and better tolerated

Answer 41

- 5HT2C - glutamate - monoamine oxidase - TCAs

Question 42

T or F: antidepressants can treat various pain states via interfering with transmission

Answer 42

T

Question 43

# PCOL of ___ (Addyi) - hypoactive ___ desire disorder - developed as an antidepressant - polypharmacology: agonist at 5HT ___ and antagonist at 5HT ___ / ___ - regional selectivity: prefrontal cortex - controversial

Answer 43

- sexual - 1A, 2A/C