Genes & Depression
1 variant of SERT is
Protective
decreases the potential for depression when exposed to stress
increases the sensitivity to to SSRIs/SNRIs if they need to be used
Response to antidepressants is said to be positive when there is a _________ improvement in sx
50 %
Name the 6 SSRIs Generic and brand
6
Fluoxetine/prozac
paroxetine/Paxil
Sertraline/Zoloft
fluvoxamine/Luvox
citalopram/Celexa
Escitalopram/Lexapro
binds at Sigma1
inhibits CYP2A & CYP34A = lots of drug to drug interactions
IR needs BID dosing
100-300 mg for anxiety & OCD
NEVER APPROVED for depression
100-200 mg/day for depression
Fluvoxamine/Luvox
SNRI MOA
most commonly prescribed after SSRIs
Works or SERT & NET to INCREASE 5HT & NE
helps with pain NET inhibition INCREASES DA ONLY in the prefrontal cortex
having the S variant of SERT
increases the susceptibility to stress and depression
linked to:
hippocampal atrophy
cognitive Sx
less tolerate to SSRIs/SNRIs
most widely used psychotropic medication
starting point for depression and anxiety
SSRIs
improves fatigue and motivation
does not do well if pt is anxious, irritable, and not sleeping
LONG half life-less withdrawal effect
long time to clear BE CARE when changing agents
effects SERT
promotes NE by inhibiting NE reuptake (effects NET)
10mg-80mg/day
antagonist at 5HT2C =increase release of NE & DA
Fluoxetine/Prozac-activating
R enantiomer mild histamine properties helps with tolerability and anxiety
QTC issues-EKG torsade's de pointe
20-40 mg/ day
Citalopram/Celexa
Name the SNRI (1 of 4)
works on SERT & NET to BOOST 5HT and NE
pro drug needs to be metabolized= CYP breaks it down to the active metabolite desvenlafaxine
GI issues with med, HELPS with migraines
XR release form decreases side effects but worsens withdrawal (electric shock feeling)
dosing 75-225 mg/day either IR or XR form
Venlafaxine/Effexor
Depression looks _________ depending on which
__________ are effected
Different, Monoamines
Over all Antidepressants can
improve mood, SI, & Psychomotor retardation
poor at improving concentration, lack of interest, and motivation
BEST FOR AGES 25-65
nhibits SERT INCREASING 5HT
Inhibits DAT INCREASING DA
binds to SIGMA 1 receptor =decreased anxiety
50-200 mg /day
DA is activating-----> go slow
increase, energy, motivation, and concentration
Sertraline/Zoloft Activating
i
S enantiomer only (histamine is removed)
Purest SSRI- ONLY SERT action
no QTC issues
least amt of drug to drug interactions
more potent than citalopram/celexa
dosing 10-20 mg /day
Escitalopram/Lexapro
Name the SNRI (1 of 4)
Active metabolite of Venlafaxine
SERT & NET Effect
decreases side effects
REDUCES VASOMOTOR SYMPTOMS for perimenopausal women
dosing 50-100 mg/day
Desvenlafaxine/Pristiq
Reduced Positive affect depression
regulated by DA& NE dysfunction
characterized by:
Decreased mood, joy, pleasure, alertness, self-confidence
When the PMHNP is prescribing SSRIs how can it be explained to the pt? (MOA short answer)
blocks SERT and increases the amount of 5HT at the synapse
overtime causes postsynaptic neurons to create more 5HT receptors (binding site)
takes 4-6 weeks with 1-2 adjustments (each 4-6 weeks)
Paroxetine
Paxil- calming
M1 effect=mild anticholinergic action -may help with anxiety
causes male sexual dysfunction d/t inhibiting nitric oxide synthetase
short half life (slow taper)
W/D sx= akathisia, restlessness, GI Sxs, dizziness, and tingling
IR 20-50 mg/day
CR25-62.5 mg/day
SERT inhibition and 5HT1A Partial Agonist (autoreceptor =balance)
1.increases 5HT effect and improves tolerability
2. GI effects worse initially but get better in 1 week
3. works faster than SSRIs
dosing 20-40mg /day
Vilaziodone/Viibryd
Name the SNRI (1 0f 4)
Like it's brother and sister, but MORE potent action at SERT than NET
helps with chronic pain
helps with cognitive symptoms of depression
can be given daily or BID 60-120mg
less withdrawal rxn than venlafaxine, taper off slowly BAD withdrawal
Duloxetine/Cymbalta
Increased Negative Affect
regulated by: 5HT & NE dysfunction
Characterized by: depressed mood, guilt, fear, hostility, irritability, and loneliness
Star D trial
1/3 of pts experience remission with 1st antidepressant
2/3 of patients improved with a trial of 4 different antidepressants (adequate trials of 12 weeks for each antidepressant)
SSRI MOA -Long Answer
Blocking SERT is main action
When 5HT transporter is blocked, 5HT is greater.
It binds to 5HT1A, Autoreceptor
in the beginning, 5HT is decreased
5HT autoreceptors become desensitized and can no longer stop blocking the amt of 5HT and it will FLOOD into the synapse
postsynaptic become desensitized and medication becomes tolerable and less side effects
Name the SNARI (4)
Venlafaxine/Effexor
Desvenlafaxine/Prestiq
Duloxetine/Cymbalta
Milnacipan/Savella
Name the SNARI (1 of 4)
not approved for depression
only used for chronic tx of pain in the US
MORE NET than SERT action= sedating and urinary hesitancy
Give BID dose 30-200mg
Milnapracin/Savella