SSRI means
Serotonin-Selective Reuptake Inhibitors
SSRI MOA
Selectively inhibit reuptake of serotonin from synaptic cleft and increase levels of 5-HT
SSRI time of action
8 weeks
***SSRI Side Effects
No anticholinergic toxicity No "cheese syndrome" Mainly just serotonin syndrome Can push a suicidal person over the edge Agitation, anxiety, panic attacks Restlessness, psychomotor retardation, mild PD Rapid muscle movement at night ***Sexual dysfunction (COMMON) N/V Diarrhea, GI cramps HYPONATREMIA
SSRI work on
Negative affect pts: depressed mood, guilt, disgust, anxiety, irritability
- Dont relieve symptoms of decreased positive affect
Positive affect means
Joy, happiness, enthusiasm, alertness, self confidence
So if you have not enough 5HT then you see
Depression, OCD, panic, bulimia
If you have too much serotonin, then you see
Anxiety, insomnia, sexual dysfunction, GI probs, serotonin syndrome (fever, tremor, seizures) and possibly cardiac valve stuff
Serotonin Syndrome can happen more often if
SSRI + MAOI
Who is at higher risk for hyponatremia with SSRIs
Older Female Lower Na Diuretics use Lower weight
SSRI Serious ADRs
NE Reuptake blockade and DA reuptake blockade
Fluoxetine Brand
Prozac
Fluoxetine classes
SERT (serotonin transporter) Reuptake Blockade
5HT 2C antagonism
What does fluoxetine do through 2c blockade?
Dis-inhibits NE And DA (increase their levels) which leads to energizing and fatigue reducing effects
Also anorexia and anti-bulimia effects (high dose)
High dose inhibition and other inhibitions with Fluoxetine (Prozac)
NET and 2D6/3A4 (many drug interactions)
Sertraline
Zoloft
Sertraline classes
DA Reuptake Blockade (weakly)
Sigma 1 Agonist
What does sertraline’s classes mean it does?
DA - improve energy and motivation (weak activating)
Signma- Anxiolytic effect
Paroxetine
Paxil
Paroxetine effects
Anxiolytic
Weak NET inhibition (good to fight depression)
Down sides to paroxetine
Inhibits 2D6
Blocks NOS (sexual dysfunction)
Big withdrawal symptoms!
Fluvoxamine
Luvox
Fluvoxamine treats
OCD and anxiety
Fluvoxamine class
Sigma 1 agonists (anxiolytic)
***Down sides to Fluvoxamine
Metabolized by 3A4 and 1A2 which are induced in smokers
Citalopram
Cipramil
Citalopram classes
SERT
Mild H1 blocker
Pros of citalopram
Better tolerated
Cons of citalopram
Mild 2D6 inhibition
S-Citalopram
Escitalopram
S-Citalopram class and pros
No anti H1
No 2D6
PURE SERT inhibitor (SSRI)
SSRI Problems with Dosing
Delayed effects Difficult to monitor Long half life and active metabolites Inter-individual variations Interactions! CI with MAOIs
SNRI means
Serotinin NE Reuptake Inhibitors
Venlafaxine
Effexor
Down sides to venlafaxine
Substrate for 2D6 and primary metabolite is also 2D6 (desvenlafaxine)
Venlafaxine side effects
Nausea
Sexual dysfunction
SSRI-like
Levomilnacipran
Fetzima
Levomilnacipran potency
NERT more than SERT
No DA
Levomilnacipran SE
Nausea Constipation Hyperhidrosis Tachycardia Sexual dysfunction Vomiting
NDRI means
NE Dopamine Reuptake Inhibitors
Buprioprion
Wellbutrin
Buprioprion works how?
Poorly defined
Weak inhibitor of both NET/DAT but metabolites are more potent
Goldilocks drug solution?
CNS activating and stimulating
Also anti-smoking drug
Down side to bupropion
2D6
Buproprion use
Pts who cannot tolerate serotonin side effects of SSRI or whose depression does not respond to 5HT boosting
Duloxetine
Cymbalta
Duloxetine
5HT and NE uptake
Duloxetine down side
2D6 inhibitor
Duloxetine used for
Chronic pain
Pain with depression
NRI means
NE Selective Reuptake Inhibitors
Examples of NRI
Atomoxetine (Strattera)
Viloxazine (vivalan)
SARI means
Serotonin Antagonist Reuptake Inhibitor
SARI MOA
Combination of SERT inhibition and 2A/2C blockade
2A/2C antagonisms + SET inhibition means
Makes serotonin output more inhibitory
Potentiates gene expression stimulated by 1A
Potentiates inhibitory action of 1A on glutamate release
Trazodone
Desyrel
Trazodone is used for
Short acting sedative antidepressant (3-6 hrs)
Down side to trazodone
3A4
NaSSA
Noradrenergic-Specific Serotonergic Antidepressant
NaSSA MOA
Release more serotonin and don’t stop releasing
Mirtazapine
Remeron
Mirtazapine class
H1 (strong sedative)
Alpha2 (enhances NE)
Blocks H1, 5HT2 and 5HT3
Typical AE
Weight gain
Vilazadone
Viibryd
Vilazadone class
SSRI
Vilazadone up side
Improved mood within one week
No reduction in sexual functioning
No weight gain
St. John’s Wort
Hypericum perforatum
- 3A4 and can cause serotonin syndrome with other antidepressants
Major depression is a result of
neuronal loss in hippocampus and prefrontal cortex and drugs stimulate neurogenesis