Monoamine hypothesis
deficiency in monoamines (serotonin, norepinephrine, dopamine) linked to depressive symptoms
developed bc of reserpine
MOA
monoaminase
enzyme that degrades serotonin, norepinephrine, dopamine
serotonin
5 HT
throughout the body
stimulates peristalsis (GI tract - 90%)
CNS (mood, sexual behavior, sleep, temp, etc.)
Cardiovascular
dopamine
CNS - reward, emotion, cognition, memory
endocrine - prolactin secretion
cardio - norepinephrine/epinephrine release
high dopamine
schizophrenia
low dopamine
parkinson’s
norepinephrine
cardiovascular (a-1= vasoconstriction, b-1 = increased HR)
fight or flight (increased RR, blood sugar, relax intestinal muscles)
CNS (concentration, alertness)
depression medication classes (6)
SSRI
SNRI
select antidepressants
TCAs
MAOis
Herbals
which class of medications are NEVER used first line
MAOi, Herbals, sometimes TCAs
how long is a “trial” of antidepressants
4-8 weeks
what other factors must be considered before starting an antidepressant?
Tapering
other things causing depression – beta blockers***
SSRI mechanism
selectively inhibits reuptake of serotonin into pre synaptic neuron (SERT receptor)
SSRI names
- Fluoxetine/Prozac
- Sertraline/Zoloft
- Paroxetine/Paxil
- Citalopram/Celexa
- Escitalopram/Lexapro
- Fluvoxamine
Fluoxetine
Prozac
Sertraline
Zoloft
Paroxetine
Paxil
Citalopram
Celexa
Escitaplopram
Lexapro
dosage of Celexa
20-40 mg/day MAX
SSRI side effects(systems/specific)
***GI (n/v, dry mouth)
CNS (sedation, insomnia, sucidial ideation )
Erectile dysfunction
hyponatremia (ADH elevation)
anticholinergic
perimenopausal women - helps hot flashes
QTc prolongation
anticholinergic symptoms
anti-SLUDGE
dry mouth, eyes, urinary retention, constipation
QT prolongation
prolonging of QT interval (normal - 400 msec, this - 500+ msec)
risk factors: medication hypokalemia)
drug interactions of SSRI
other serotonergic medications
+CYP drug
Fluoxetine drug interactions
CYP2C19 inhibitor
clopidogrel (2C19 substrate - unable to work if taken with Flux.)
also tamoxifen
SNRI (drug list)
- Venlafaxine/Effexor
- Descenlafaxine
- Duloxetine/Cymbalta
- Levonmillnacipran
SNRI mechanism
selectively inhibits reuptake of serotonin and norepinephrine
NET and SERT
SNRI side effects
GI (n/v/dry mouth)
CNS (insomnia, libido, suicidal ideation)
Erectile dysfunction
** Increased BP (N.e.) (usually not clinically sig. but keep in mind for uncontrolled HTN)
specific duloxetine side effects
Anti-cholinergic symptoms and liver toxicity
SNRI drug interactions
other seroternergic meds
duloxetine specific CYP1A2
duloxetine drug interactions
CYP 1A2 substrate
with CIPRO (1A2 inhibitor) it competes with the substrate and decreases its ability to work
other indications
duloxetine
diabetic neuropathy
fibromyalgia
chronic musculoskeletal pain
other indications
venlafaxine
off table diabetic neuropathy
venlafaxine
effexor
duloxetine
cymbalta
bupropion (gen., mechanism)
other medication
used after SNRI
inhibits norepinephrine and dopamine reuptake (no MAO or serotonin activity)
NET and DAT receptor blocker
bupropion brand name
wellbutrin
bupropion side effects
increased seizure risk*** (dose related)
CNS function (headache, insomnia, irritability, decreased appetite, improved sexual dysfunction, smoking cessation (Zyban))
bupropion drug interactions
MAO inhibitors – can lead to hypertensive crisis
other antidepressant list
- mirtazapine
- vortioxetine
- trazodone
- nefazodone
- vilazodone
mirtazapine
pre-synaptic a-2 agonist (increased Ne and serotonin)
pronounced sedation (can be used in insomnia) weight gain
vortioxetine
inhibits serotonin reuptic (5HT1A agonist)
improved cognition, SE of SSRI
brand name only
trazodone
inhibits serotonin reuptake, 5ht2A antagonist
causes orthostatic hypotension, sedation, priapism
nefazone
inhibits serotonin reuptake , 5HT2A antagonist
less risk of trazodone SE
can cause liver toxicity, potent CYP3A4 inhibitor
vilazodone
inhibits serotonin reuptake, 5HT1 agonist
clinical advantage unknown, brand name only
TCA drug list
- amitriptyline
- imipramine
- despiramine
- nortriptyline
TCA mechanism
selectively inhibits reuptake of serotonin and norepinephrine
antihistamine and anticholinergic effects
Na channel blocker***
TCA side effects
anticholinergic orthostatic hypertension cardiotoxicity narrow therapeutic index -- suicidal ideation GI/CNS
TCA overdose management
sodium bicarbonate for cardiac toxicity
mixed with dextrose
TCA drug interactions
antiocholinergic agents
other serotonergic medication
MAOi drug list
- isocarboxazid
- phenelzine
- selegilline** parkinson’s
- tranylcypromine
MAOi mechanisms
increases endogenous concentrations of norepinephrine, dopamine, serotonin they inhibition of monoamine oxidase
not first therapy – reserved for patients refractory to SSRI, SNRI, bupropion
MAOi side effects
orthostatic hypotension
CNS (decreased libido, anorgasmia)
weight gain
hypertensive crisis
MAOis hypertensive crisis**
avoid tyramine containing foods (breaks down into n.e. and dopa)
metabolism is inhibited by MAOis so there is an excess – causes HTN
treat with alpha blocker
drug interactions MAOi
other srotonergic meds (2 week washout)
antihypertensive meds
serotonin syndrome
excess of serotonin
can be idiosyncratic, accidental interaction or intentional over dose
symptoms of serotonin syndrome
tremor, hyperreflexia
muscle rigidity
hyperthermia
agitaiton/diaphoresis
increased bowel sounds (diarrhea)
serotonin syndrome management
discontinue meds
monitor the vitals
serotonin antagonist - cyproheptadine
cyproheptadine
non-sepcfic antagonist of 5HT-1 and 5HT-2 receptors
ONLY oral (may be given via NG tube)
can be used in allergies and anorgasmia
resistant depression treatment
second generation antipsychotics
ariprprazole, brexipiprazole, quetiapine
olanzapine/fluoxetine are FDA approved
herbals for depression
SAMe- S-adenosyl methionine
st. john’s wart
SAMe
Metabolite
found that there was a remission and adverse events decreased
BEERs list
anticholinergic (urinary retention, constipation)
chronic seizures
SIADH
SSRIs
pregnancy and depression meds
maternal depression adversely affects child development
both meds and untreated cause problems os must weigh risk v. benefits
