depression Flashcards
types of depression
- ___ (60%)
- major depressive disorder (25%)
- bipolar affective (15%)
common mental illness of general population
- 10%, underdiagnosed, untreated, suicidal
- reactive
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
- sleep, menstrual
- concentration
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
- reserpine
- alcohol
- opiates
- corticosteroids, estrogen
biogenic amine hypoothesis of depression
- reserpine causes depression by depleting ___ and ___ from vesicles
- genetic polymorphisms in ___ promoter
- alterations in 5HT1A/2C and a2 receptors
NE, 5HT
SERT
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
- HPA
- CRF
- ACTH
- cortisol
- CRF
- desensitize
CRF1 receptor
- arousal
- ___ like behavior
- disruption of ___ behaviours
- disruption of ___
CRF2
- slow adaptive recovery
- ___ suppression
- anxiety
- sexual
- sleep
- appetite
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
- plasticity
- decrease
- hippocampus
- antidepressant
- volume
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
- steroid
- cortisol
- monoamine, downregulation
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
increase
activation
adaptation
MOA: MAO-i
- ___ and ___ are degraded by monoamine oxidase
- by inhibiting, we increase the amount transmitted by vesicles into the synapse
- NE, 5HT
MAO-i
non-selective:
- ___ (Nardil)
- ___ (Parnate)
MAO-B selective:
- ___ (Eldepryl/Ensam)
- ___ (Xadago)
MAO-A selective:
- ____ (Manerix)
- phenelzine
- tranylcypromine
- selegiline
- safinamide
- moclobemide
MAO-i Structures
phenelzine
similar to amphetamine
MAO-i Structures
tranylcypromine
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 ___
- tyramine
- St. John’s Wort
- TCAs, SSRIs, L-DOPA
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
increase
- 2
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 ___
reuptake
- sedation
- heart
tertiary amines
___ (Tofranil)
- metabolized to desipramine
- enuresis and ADHD
___ (Elavil)
- metabolized to nortiptyline
imipramine
amitriptyline
tertiary amines
trimipramine (Surmontil)
clomipramine (Anafranil)
- used for ___
____ (Adapin, Sinequan)
OCD
doxepin
clomipramine - causes orgasm when yawning
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
- desipramine
- nortriptyline
- protriptyline
- maprotiline, NET
- less, less, less, less, less
- CV, gain
- increased
SSRI
Drug
- ___ (Prozac): little autonomic SE, no ___
- ___ (Luvox)
- ___ (Paxil)
- ___ (Zoloft)
- ___ (Celexa)
- ___ (Lexapro): isomer of citalopram
- fluoxetine, sedation
- fluvoxamine
- paroxetine
- sertraline
- citalopram
- escitalopram
SSRI
T or F: there is a structural pattern to SSRIs
False: all over the place
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
- anxiety
- zaps, sweating
- MAOIs, tramadol
- cyproheptadine, benzodiazepines
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)
vilazodone
- similar
- sexual
vortioxetine
Tetracyclic and Unicyclic
___ (Ludiomil)
- ___ inhibitor
___ (Ascendin)
- ___ inhibitor
- ___ antagonists
maprotiline
- NET
amoxapine
- NET
- D2
Tetracyclic and Unicyclic
___ (Remeron)
- a2, __ , 5HT__ , 5HT __ antagonists
mirtazapine
- H1
- 5HT2 , 5HT3
Tetracyclic and Unicyclic
___ (Wellbutrin)
- ___ inhibitor
- ___ and ___ inhibitor
- also treat GAD
- “ ___ “ for smoking cessation
bupropion
- DAT
- NET, SERT
- Zyban
5-HT2 antagonists/SERT inhibitors
___ (Dyserel)
- ___ antagonist
- weak ___ inhibitor
- off label ___ (a1, H1, with 5HT2)
trazodone
- 5HT 2A
- SERT
- hypnotic
Have to take huge doses as antidepressant, super sedating
SNRIs
___ (Effexor)
- ___ and __ inhibitor
- treats GAD and panic disorder
- might be useful for diabetic ___ and ___ prophylaxis (?)
venlafaxine
- NET, SERT
- neuropathy, migraine
SNRIs
___ (Pristiq)
- ___ and ___ inhibitor
- useful for vasomotor symptoms associated with ___ (?)
desvenlafaxine
- NET, SERT
- menopause
SNRIs
___ (Cymbalta)
- ___ and ___ inhibitor
- treats GAD
- treats peripheral ___
duloxetine
- NET, SERT
- neuropathy
SNRIs
___ (Ixel)
- ___ and ___ inhibitor
- approved for ___
milnacipran
- NET, SERT
- fibromyalgia
SNRIs
___ (Fetzima)
- active enantiomer or ___
- ___ and ___ inhibitor
levomilnacipran
- milnacipran
- NET, SERT
NSRIs
___ (Vestra, Edronax)
- possible less side effects than ___
- not available in US
reboxetine
- Prozac
NSRIs
___ (Straterra)
- originally intended to be an antidepressant (not approved)
- used for ___
atomoxetine
- ADHD
Selectivity Profiles
___ number = more selective
- amitriptyline more selective for ___
- nortriptyline more selective for ___
- escitalopram is super selective for ___
smaller
- 5HT
- NE
- 5HT
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
- tesofensine, brasofensine
- tesofensine
rapidly acting antidepressants: NDMA antagonists
- ___ subanesthetic doses
- ___ (muscarinic and NMDA antagonists)
- Lanicemine “low trapping”
- GLYX-13 partial NMDA antagonists
- ketamine
- scopolamine
clinical used NMDA antagonists
___ - subanesthetic doses
___ (Spravato) - in conjunction with oral antidepressant
- CNS effects: ___ , drug interactions
- intranasal, phased dosing
- available only through ___ program
ketamine
esketamine
- depression
- REMS
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
- fluoxetine, paroxetine, venlafaxine
- brexanolone, GABA A
Brexanolone (Zulresso)
- ___ levels increase during pregnancy
- ___ receptors desensitize (?)
- levels return to normal postpartum
- brexanolone resensitizes receptors
- ___ program
- ___ hr infusion ($20,000-30,000)
- allopregnanolone
- GABA-A
- REMS
- 60 hr
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
- 5HT2C
- glutamate
- monoamine oxidase
- TCAs
T or F: antidepressants can treat various pain states via interfering with transmission
T
PCOL of ___ (Addyi)
- hypoactive ___ desire disorder
- developed as an antidepressant
- polypharmacology: agonist at 5HT ___ and antagonist at 5HT ___ / ___
- regional selectivity: prefrontal cortex
- controversial
- sexual
- 1A, 2A/C
