Antidepressant Drugs Flashcards
5 R’s of antidepressant efficacy
- Response = ≥50% reduction in sx
- Remission = sx free
- Recovery = 6-12 months of ongoing remission
- Relapse = return of symptoms after remission but before recovery
- Recurrence = return of symptoms after recovery
average response time to antidepressants
8 weeks
if no response after this time, may switch to another antidepressant with a different MOA
describe the withdrawal sx of antidepressants
FINISH: flu like sx insomnia nausea imbalance sensory disturbances hyperarousal
SSRI MOA
selective seratonin reuptake inhibitors
via SERT
what are the SSRIs?
citalopram escitalopram fluoxetine paroxetine sertraline ** ya girl's med vilazodone vortioxetine
which SSRI is also a partial 5HT1a agonist?
vilazodone
which SSRI is also a partial 5HT1b agonist, full 5HT1b agonist and full 5HT1d antagonist?
vortioxetine
why are SSRI’s preferred over TCAs?
much less impact on histamine, muscarinic and adrenergic receptors
SSRI common side effects
sedation
sexual dysfunction
weight gain
acute withdrawal reactions
SSRI rare side effects
QT prolongation
hyponatremia
serotonin syndrome
suicidality
sx of serotonin syndrome
sweating
hyperreflexia
akathisia/myoclonus
shivering/tremors
which SSRI is most likely to cause drug interactions?
fluoxetine – strong CYP450 inhibitor
SNRI MOA
selective serotonin and norepinephrine pre-synpatic reuptake inhibitors
serotonin via SERT
norepi via NET
5HT > NE
3˚-amide TCA MOA
inhibit both NE/5HT equally
*exception = clomipramine/amtriptyline 5HT > NE
2˚-amide TCA MOA
inhibit NE > 5HT
what are the SNRIs?
All TCAs Desvenlafaxine Duloxetine Venlafaxine Levomilnacipran
what are the 3˚-amide TCAs?
"ACID" Amitriptyline Clomipramine Imipramine Doxepin
what are the 2˚-amide TCAs?
Amoxapine
Desipramine
Nortryptyline
which receptors are also affected by TCAs?
histamine
muscarinic
adrenergic
TCA activation of adrenergic receptors causes which side effects?
tachycardia
orthostatic hypotension
dysrhythmias
TCA activation of muscarinic receptors causes which side effects?
dry mouth
urinary retention
constipation
blurred vision
TCA activation of histamine receptors causes which side effects?
sedation/fatigue
dizziness
seizures
3 C’s of TCA overdose
Coma
Cardiotoxicity (Conduction abnormalities)
Convulsions
SNRI side effects
relatively similar to SSRI’s but less risk of sexual dysfunction
Trazadone and Nefazodone MOA
SSRI + block post-synaptic a1 receptors on NE and 5HT receptors
Mirtazapine MOA
blocks pre-synaptic a2 receptors on NE and 5HT neurons + blocks post-synaptic 5HT receptors
*no SERT/NET activity
side effects of SARAs
sedation
orthostatic hypotension
weight gain
NDRI MOA
selectively inhibits pre-synaptic reuptake of NE and DA via NET and DAT
also evidence of an enhanced pre-synaptic release of NE and DA via VMAT2
what is the NDRI?
bupropion
bupropion side effects
agitation insomnia HTN tachy tremors weight loss seizures
MAOIs MOA
inhibition of monoamine oxidase which increases monoamines in neuronal vesicles and increases amounts of NE, 5HT and DA
which MAOI is the only non-selective agent
selegiline (patch)
what are the MAOI?
isocarboxazid
phenelzine
selegiline
tranylcypromine
MAOI side effects
orthostatic hypotension
sexual dysfunction
weight gain
insomnia/agitation
what is the primary concern of patients taking MAOIs?
hypertensive crisis
*MAOIs inhibit tyramine metabolism –> causes catecholamine release
which MAOI has the lowest risk of a hypertensive crisis?
selegiline
misc antidepressants
esketamine - NMDA antagonist
brexanolone - GABAa agonist
indications for giving eskatmine
NMDA-ant: treatment-resistant depression in conjunction with ongoing antidepressant therapy
*nasal administration
indications for giving brexanolone
post-partum depression - identical to endogenous allopregnanolone
*60 hr IV administration
what are the mood stabilizers?
carbamazepine
lamotrigine
valproic acid
lithium
why are anti-seizure meds used as mood stabilizers?
exact MOA unclear
the just fuckin work ok?????
lithium MOA
- alters brain structures
- neurotransmitter modulation
- intracellular changes
which brain structures are affected by lithium?
anterior cingulate cortex
superior temporal gyrus
ventral prefrontal cortex
hippocampus
how does lithium modulate neurotransmitters?
inhibits DA
downregulates NMDA receptor
increases GABA levels
what are the intracellular effects of lithium?
inhibits IPPase and IMPase
inhibits PKC, MARCKS and GSK3
activates CREB transcription factor (neuroprotective)
describe the renal effects of lithium
lithium enters principal cells of collecting duct via Na channels
lithium accumulation interferes with ADH-mediated effects
can lead to resistance to ADH resulting in polyuria and polydipsia
lithium renal toxicity can be confused with what other condition?
nephrogenic diabetes insipidus
what drugs interact with lithium?
diuretics
ACEIs
NSAIDs
lithium side effects
tremor mental confusion dizziness sedation thyroid goiter leukocytosis seizures serotonin syndrome
lithium indications
mania/bipolar 1
augmentation in unipolar depressive patients
off label: reduced risk of suicide
indications for anti-seizure mood stablizers
Bipolar 1 and 2
- lamotrigine for 1 or 2
- valproic acid and carba for 1 only
