Antidepressants and Mood stabilizers Flashcards
Most antidepressants are also for other ?
mental health conditions
what medication is used as an antidepressant but also for nicotine withdrawal
bupropion
what medication is used as an antidepressant but also for Enuresis
imipramine
what medication is used as an antidepressant but also for diabetic peripheral neuropathy, fibromyalgia, and chronic musculoskeletal pain
duloxetine
what medication is used as an antidepressant and also for stress incontience
duloxetine
what is enuresis
urinary incontience (loss of bladder control)
what is the first line treatment non-pharmacologic for depression
psychotherapy
what is the monoamine depression hypothesis ?
Norepinephrine, serotonin, dopamine, glutamate, and GABA are all dysregulated and out of wack
what is the neurotrophic depression hypothesis
there is a decrease in brain derived neurotrophic factor and neuronal plasticity
what is the steroid depression hypothesis
this is when glucocorticoids, thyroid hormones and sex hormones ( estrogen/testosterone) are out of wack causing depression
what are the 5 R’s in general antidepressant efficacy
Response
Remission
Recovery
Relapse
Recurrence
what is response
there is greater than or equal to 50% reduction in symptoms from baseline (not well, not the end goal)
what is remission
this is very low to no symptoms at all, better and well with a healthy state of functioning
what is recovery
6-12 months of ongoing remission (not cured)
what is relapse
return of symptoms after remission
what is recurrence
return of symptoms after recovery
how long does it take for antidepressants to kick in?
3-8 weeks depending on many factors
goal of antidepressant therapy is ?
remission/recovery
What are the classes of drugs used to treat depression
SSRis
SNRis
NDRis
NMDA antagonists
SARAs
Neurosteroids/Gaba modulator
MAOIs
what drugs are in the drug class SSRIs?
Citalopram
Escitalopram
FLuoxetine
Paroxetine
Sertraline
Vilazodone (2)
Vortioxetine (2)
what does SSRI mean
serotonin selective reuptake inhibitor (pre-synaptically)
MOA of SSRIs?
selectively inhibitor the presynaptic reuptake of serotonin via SERT
as a class, SSRIs are more _ than other classes of antidepressants
specific
Vilazodone and Vortioxetine are both SSRis but what is their 2nd mechanism of action
that are partial or full agonists at 5HT1 (which is an inhibitory G protein )
SSRIs as a class have much less impact on _ , _, and _ receptors
histamine, muscarinic, adrenergic
which SSRi has the most anticholinergic side effect ?
paroxetine
side effects of SSRIs
CNS depression (sedation or insomnia)
sexual dysfunction (due to serotonin)
weight gain/loss
hyponatremia
QT prolongation
serotonin syndrome
what is serotonin syndrome
this is dose dependent disorder due to an increased level of serotonin often when given concurrently with multiple serotonin affecting drugs
symptoms of serotonin syndrome
abdominal pain/diarrhea
flushing
hyperreflexia
mental status changes
shivering
rhabdomyolysis/renal failure
cardiovascular shock/death
all antidepressants either are known to or can be associated with a withdrawal syndrome known as?
FINISH
flu-like symptoms
insomnia
nausea
imbalance
sensory disturbances
hyperarousal
all antidepressants have a black block warning of?
suidical ideations, behaviors, and actions (not completions)
**highest risk in less than 24 years old
what is the strongest CYP450 drug inhibitor in the SSRI class (dont prescribe if they are on a shit ton of medicines already)
fluoxetine
_ (SSRI) is a potent 2D6 inhibitor
Paroxetine
what are the mild/low drug inhibitors in the SSRi class
citalopram, escitalopram, sertraline, vilazodone, vortioxetine
which 2 SSRIs have active metabolites
fluoxetine (long half life)
sertraline (short half life)
what are the SNRIs used to treat depression and what do they do
All the TCA’s and Desvenlafaxine, duloxetine, venlafaxine, levomilnacipran, amoxapine
they work by selectively inhabiting the reuptake of both serotonin and norepinephrine
what’s the difference between 3 amine and 2 amine in the SNRI class (TCA)
3 amine have relatively equal impact on both serotonin and norepinephrine
2 amine has more impact on norephinephrine
**most other SNRIs have more impact on serotonin than NE
which SNRI (serotonin and norephinephrine) also has dopamine antagonism
amoxapine
which SNRI (serotonin and norephinephrine) also has dopamine antagonism
amoxapine
D2 antagonist
what are the 3-amine TCAs
(have more serotonin activity)
amitriptyline
clomipramine
doxepin
imipramine
trimipramine
what are the 2 amine TCAS
amoxapine, nortiptyline, desipramine, protryptyline
TCAs also block other receptors like
histamine (H1), muscarinic (cholinergic) and A1 (adrenergic)
-3 amines more often
alpha (adrenergic) stimulation from TCAs can cause
tachycardias, orthostatic hypotension, dysrhythmias
muscarine stimulation from TCAs can cause? (anti cholinergic)
dry moth, urinary mention, constipation, blurred vision, increased IOP
histamine stimulation from TCAs can cause
sedation, fatigue, seizures
overdose of TCA 3 c’s (in the ER)
coma, cardiotoxicity (conduction abnormalities), convulsions
(quinidine like effect)
non TCA SNRIs have side effects similar to SSRIs with generally less risk of _
sexual dysfunction
SNRIs due to NE can cause
HTN, agitation, nervousness
what are SARAs used to treat depression
Serotonin Adrenergic (NE) receptor antagonsits
trazodone and nefazodone and mitrazapine
SARAs trazadone and nefazadone block the A _ receptors on the adrenergic neurons leading to _ and the post synaptic _ receptors providing efficacy
1
side effects
5-HT2
trazodone is typically used when?
to provide H1 blockade and cause sleep
it is a weak SERT blockade
nefazadone has _ toxicity and is usually used for what
hepatic
sleep (H1 blockade)
which SARA will block presynaptic a2 receptors and Serotonergic receptors and block post synaptic 5HT 2/3 receptors
Mitrazapine (great add on)
**does not have SERT.NET activity
causes H1 blockade
what are the side effects of SARAs
sedation
weight gain- mitrazapine
orthostatic hypotension- trazodone
hepatotoxicity- nefazodone
what are NDRIs
Noreepineprhine Dopamine Reuptake inhibitors
- inhibit presynaptic reuptake of NE and dopamine
they also work to enhance presynaptic release of NE and DE though its effects on VMAT2
what drug is considered a NDRI
Busproprion (destromethopran too)
side effects of busproprion ( NDRI)
stimulating! (wake up)
agitation , insomnia, hypertension, tachycardias, tremors
weight loss
seizures
what is the mechanism of action of MAOIs
irreversible block monoamine oxidase inhibitors which increases the levels of monoamines in the neuronal vesicles leading to increased amounts of NE, 5-HT, and dopamine
all oral expect segeline (B selective)
what is a MAOI that is B selective and given in a patch form for depression
selegiline
what are the drugs in the MAOi class
Isocarbaxazid
Phenelzine
Selgeline
tranylcypromine
which MAOIs have a stimulant like effect (2)
tranycypromine and selegiline
what is the most side effect of MAOIs (broad spectrum increase in neurotransmitters)
hypertensive crisis
dont forget serotonin syndrome**
symptoms of hypertensive crisis
severe headache, anxiety, sweating, nosebleeds, tachycardia, chest pain, changes in vision and breath, confusion, N/V
how does MAOIs cause hypertensive crisis
they inhibit MAO-A which is necessary for tyramine metabolism in the GI tract
tyramine containing substances (foods) in our stomach and tyramine can induce significant catecholamine release leading to hypertensive crisis
- need dietary counseling***
NMDA antagonists for depression MOA
- drug in the class?
when do you use the inhalation type?
NMDA is an ionotropic channel ; prevents Na+ from coming in and depolarization (glutamate)
Esketamine
Dextromethrorphan
-treatment resistant depression in conjunction with ongoing antidepressant therapy with acute suicidal ideations/behaviors
(nasally administered)
if you are going to give esketamine the patient is observed _ hours post dose looking at blood pressure and cognitive impairment
2
what is the MOA of the Neurolosteroids/GABA modulator
what drug is this?
they are GABA a receptor positive allosteric modulators that are identical to endogenous alloprehnalolne (these levels drop in postpartum period)- increases neuronal GABA inhibition
Brexanolone
when and how do we use Brexanolone (Neurosteroid/GABA modulators)
for post-partum depression
60 hour IV administration with lots of monitoring
what are the mood stabilizer families that are used to treat Bipolar I and Bipolar II
Anti-seizure agents
miscellaneous
what are the anti seizure agents that are used as mood stabilizers in Bipolar disorder
carbamazepine
lamotrigine
Divalproex/Valproate
Valproic acid
what is the miscellaneous mood stabilizer used to treat bipolar disorder
lithium
BIPOLAR PATIENTS MUST BE ON?
mood stabilizer!!!!!!! not antidepressant (only treating one pole)
what are the 3 MOA in lithium (broad)
brain structure, neurotransmitter modulator, intracellular changes
lithium inhibits and stimulates what receptors
dopamine receptor (D2) GI and Gs (inhibits)
NMDA blocker
stimulates GABA
intracellular changes due to lithium
blocks IPPase and IMPase which depletes MI-myoinositol (too much of this in the manic state) (decrease PIP2 pathway)
inhibits PKC, GSK-3 and MARCKS
decreased PKC facilitates _ release
5HT
decreased GSK-3 increases _ which is neuroprotective
B catenin
lithium facilitates production of _ and _ which are both neuroprotective
CREB/BDNF and BCl-2
side effects of lithium
monovalent ion and competes with Na+ for reabsorption
leads to decreased aldosterone and vasopressin effects along with RESISTANCE to ADH
leads to polyuria/polydipsia (nephrogenic diabetes insipidus)
tremor
confusion
leukocytosis
what other drugs can interact with lithium
anything that impacts Na/K
ace inhibitors, diuretics. NSAIDS
what is the therapeutic window of lithium
its narrow
0.6-1.5
when do we use lithium
acute and maintenance of mania/bipolar I disorder
reduce risk suicide
what are the 3 mood stabilizer initially developed as anti seizure agents utilized to treat bipolar disorder
valproic acid/divalproex/valproate
lamotrigine
carbamazepine
MOA of valproid acid/divalproex
decreases myo-inositol-1, PKC< GSK-3, MARCKS
therapeutic range for valproic acid
60-120mcg/ml
pharmacokinestics of valproic ACID-
inhibits _ isozyme and _ glycoprotein and induces a few different _ isozymes
it _ hepatic enzyme uridine glucuronotransylferases (UGT)
CYP450
P
CYP450
inhibits
side effects of valproic acid
thrombocytopenia, dizziness, agitation, pancreatitis, increased ammonia levels
valproid acid indications
acute and maintenance of mania/bipolar disease
MOA of carbamazepine
decrease inositol (MI)
therapeutic window of carbamazepine
6-12 mcg
carbamezapine is a broad _ of CYP450
inducer
carbamazepine _ hepatic enzyme UGT
induces
side effects of carbamazepine
leukopenia, neutropenia, thrombocytopenia
hypocalcemia and osteoporosis
indications for carbamazepine use
acute and maintenance treatment of mania/mixed bipolar disorder
MOA of lamotrigine
(4)
blocks NMDA
decreases GSK-3 and increases BDNF
5HT1a agonist down regulating SET (serotonin reuptake)
5-HT2a agonists increasing NET blockade (NE reuptake )
metabolism of lamotrigine is reduced my
valproic acid
metabolism of lamotrigine is increased by
carbamazepine
side effects of lamotrigine
conduction abnormalities, dizziness/vertigo
indications for lamotrigine use
maintenance of bipolar I disorder (esp .with mostly depressive symptoms )
