Anti-depressants Flashcards
depression is defined as having ____ or more of the symptoms in the same ____ week period
5 or more symptoms, 2 week period
Gold standard for MDD diagnosis
Structured Clinical Interview for DSM-V
interview assessment for depression
Hamilton Depression Rating Scale
2 self-administered screening tools
Beck Depression Inventory, Edinburgh Postnatal Depression Score
Having a first degree relative with MDD increases risk ____x with _______ onset and recurrence
2-4x, earlier onset
5 causes/risk factors for MDD
temperament, environment, genetic, gender, cultural
Depression prevalence is higher in which gender
females
2 environmental risk factors for MDD
adverse childhood experiences, stressful life events
3 health statuses that could cause depression
hypothyroidism, cancer, pain disorders
depression can lead to death by
suicide
which hypothesis suggests that depression is related to a deficiency in serotonin, NE, and dopamine
monoamine hypothesis
the monoamine hypothesis suggests that depression is related to a deficiency in _________, _________, and __________
serotonin, norepinephrine, and dopamine
evidence for Monoamine hypothesis: depletion of monoamines by __________ can _________ depression
reserpine, induce depression
Reserpine is a _______ inhibitor and can ______ monoamines which _______ depression
VMAT2 inhibitor, deplete monoamines, induce depression
dietary ______ (a precursor of _______) is required for effect of SSRIs
tryptophan, serotonin precursor
the neurotropic hypothesis suggests that changes in _______ factors (especially _______) appear to play a major role in depression
trophic factors, BDNF
BDNF stands for
brain derived neurotropic factor
which hypothesis suggests that a decrease in trophic factors leads to depression
neurotropic hypothesis
stress and pain are associated with a ______ in BDNF and cause _______ changes in the brain
decrease, structure
major depression is associated with _____% loss in hippocampal volume
5-10%
chronic administration of antidepressants _______ BDNF —> _______ neurogenesis
increase BDNF, increased neurogensis
depressed patients often have _______ glutamate in CSF and cortex
elevated
chronic antidepressant use ________ glutamate transmission
decreases
stress ________ the release of glutamate in the brain; antidepressants ________ this
increases, decrease
Ketamine is a _____ receptor antagonist and has antidepressant effects
NMDA (glutamate receptor)
what is the glutamate receptor
NMDA
which drug is an NMDA Receptor antagonist
Ketamine
MDD is associated with ______ cortisol and altered functioning of _____
elevated coristol, HPA axis
5 drug classes
MAOi, Tricyclics, SSRI, SNRI, Atypical
3 MAOIs
Phenelzine, Tranylcypromine, Selegiline
class of Phenelzine
MAOi
class of Tranylcypromine
MAOi
class of Selegiline
MAOi
which MAOi is also used in Parkinsons and why
Selegiline, has higher affinity for MAO-B
2 types of Tricyclics
tertiary amines and secondary amines
5 Tricyclic tertiary amines
Amitriptyline, Clomipramine, Doxepin, Imipramine, Trimipramine
5 tricyclic secondary amines
Amoxapine, Desipramine, Maprotiline, Nortriptyline, Protriptyline
class of Amitriptyline
Tricyclic (tertiary)
class of Clomipramine
Tricyclic (tertiary)
class of Doxepin
Tricyclic (tertiary)
class of Imipramine
Tricyclic (tertiary)
class of Trimipramine
Tricyclic (tertiary)
class of Amoxapine
Tricyclic (secondary)
class of Desipramine
Tricyclic (secondary)
class of Maprotiline
Tricyclic (secondary)
class of Nortriptyline
Tricyclic (secondary)
class of Protriptyline
Tricyclic (secondary)
are tertiary or secondary Tricyclics more selective for inhibiting NE reuptake
secondary
class of Citalopram
SSRI
class of Escitalopram
SSRI
class of Fluoxetine
SSRI
class of Fluvoxamine
SSRI
class of Paroxetine
SSRI
class of Sertraline
SSRI
3 SNRIs
Venlafaxine, Atomoxetine, Duloxetine
class of Venlafaxine
SNRI
class of Atomoxetine
SNRI
class of Duloxetine
SNRI
active metabolite of Venlafaxine
Desvenlafaxine
4 atypical antidepressants
Bupropion, Mirtazapine, Nefazodone, Trazodone
class of Bupropion
atypical
class of Mirtazapine
atypical
class of Nefazodone
atypical
class of Trazodone
atypical
indication of Bupropion
smoking cessation
4 non-pharmacological treatments
psychotherapy, electroconvulsive therapy, transcranial magnetic stimulation, deep brain stimulation
4 off label indications of antidepressants
pain disorders, PMDD, vasomotor symptoms, stress urinary incontinence
7 FDA approved indications of antidepressants
MDD, panic disorder, GAD, PTSD, OCD, bulimia, smoking cessation
enzyme that breaksdown serotonin, 5HT
monoamine oxidase
MOA of monoamine oxidase inhibitors
inhibit MAO —> increase presynaptic NE and 5HT available for relase
MOA of SSRIs
inhibit presynaptic SERT —> decrease 5HT reuptake —-> increase 5HT in synapse
SSRIs: inhibit presynaptic _______, _______ 5HT reuptake, _______ 5HT in synapse
SERT, decrease reuptake, increase 5HT
MOA of tricyclics and SNRIs
inhibit presynaptic NET —> decrease reuptake —-> increase amount in synapse
tricyclics and SNRIs inhibit presynaptic ______
NET
Tricyclics also block _____ which decreases _____ signaling and increases _____ signaling
alpha1 receptors, decreases IP3, increases NE
serotonin syndrome can be caused by an overdose of
antidepressants
Using more than 1 at the same time, Not properly weaning from one before starting another
most antidepressants should be D/C at least _____ weeks before starting a new one
2 weeks
long half life serotonergic reuptake inhibiting agents (ex: ________) should be D/C at least ____ weeks before MAOI is initiated
Fluoxetine, 4-5 weeks
do secondary or tertiary amines have more side effects
tertiary
which class has the best side effect profile
SSRIs
route of administration is almost always ______
oral
SSRIs are generally ______ and _______ absorbed and survive first pass effect
rapidly and well absorbed
SSRIs have a ______ bioavailability (____% for sertraline to ____% for Fluvoxamine)
high, 45% - 90%
peak plasma conc ____ hours after administration
4-6 hours
most antidepressants are _______ protein bound, which _______ distribution
highly, decreases
SSRIs are ________ which _______ distribution. (______ volume of distribution)
lipophilic, increases, large VOD
______ is the primary metabolic enzyme for most antidepressants
CYP2D6
Exceptions to metabolism: _________ and __________ which are metabolized by CYP____ and _____
Citalopram and Escitalopram, CYP3A4 and 2C19
_________ and _________ have active metabolites
Fluoxetine and Sertraline
antidepressants are excreted _______
renally (adjust dose in renal failure)
antidepressants have a ______ half life. makes _______ dosing appropriate
long half life, once daily dosing
food-drug interactions: MAOIs + _______ containing foods
tyramine
what types of food contain tyramine
fermented, cured, aged, spoiled
Tyramine is metabolized by _____
MAO
MAOIs ________ tyramine metabolism —> _______ systemic tyramine absorption —> tyramine taken up into adrenergic nerve endings —> release of ________ into blood vessels —> vessel _______ —> ______ blood pressure —> __________ crisis
decreases metabolism, increase absorption, catecholamines, vessel constriction, increase BP, hypertensive
3 CYP2D6 inhibitors
Fluoxetine, Paroxetine, Duloxetine
4 CYP3A4 inhibitors
Fluvoxamine, Nefazodone, Sertraline, Fluoxetine
what 3 things are CYP3A4 substrates
Citalopram, Escitalopram, TCAs
Substrates of CYP2D6
TCAs, Trazodone, Paroxetine, Duloxetine, Venlafaxine, Bupropion, Mirtazapine
4 patient factors
sex, age, race/culture, sexual orientation
antidepressants are wrongfully thought of as _________ in many cultures
Addictive
BBW for antidepressants
increased risk of suicidal thinking in children, adolescents, and young adults
__________ is contraindicated in pregnancy due to __________ malformation in fetus
Paroxetine, cardiac malformation
best course of treatment for antidepressants during pregnancy
continue antidepressant therapy
_________ circulating glucocorticoids can cause _____ birth weight
increased, low birth weight
indication of atomoxetine
ADHD
which tertiary tricyclic is LEAST LIKELY to cause seizures
Doxepin
main risk with MAOIs
Serotonin Syndrome
a person will develop ________ to MOST side effects of antidepressants
tolerant (GI, sedation)
2 main side effects of SSRIs
GI effects and Sexual effects
side effects of tertiary tricyclics
seizures, sedation, hypotension, Anti-ACh effects, weight gain, sexual effects, cardiac effects
what are ACh side effects
dry mouth, pupil dilation, sensitive to light, hot/flushed/dry skin, increased intraocular pressure
what side effect is very common amgonst antidepressants
sexual (ED, decreased libido)
symptoms of Serotonin Syndrome
Hyperthermia, muscle rigidity, myoclonus, tremors, autonomic instability, confusion, irritability, agitation
can process to coma/death
antidepressant monotherapy should NOT be prescribed for patients with ________
bipolar disorder
why should antidepressant monotherapy not be prescribed for bipolar pt
can induce manic state
antidepressants have a delayed effect; can take ______ weeks to take effect
4-6 weeks
antidepressant can cause physical _______, which leads to withdrawal
dependence
NOT ADDICTION!!!
be very careful when switching between antidepressant classes to avoid ________
serotonin syndrome
therapeutic range of citalopram
20-40
therapeutic range of escitalopram
10-20
therapeutic range of fluoxetine
20-80
therapeutic range of fluvoxamine
100-200
therapeutic range of paroxetine
20-40
therapeutic range of sertraline
100-150
therapeutic range of TERTIARY tricyclics
100-200
therapeutic range of protriptyline
15-40
therapeutic range of amoxapine
200-300
therapeutic range of desipramine
100-200
therapeutic range of maprotiline
100-150
therapeutic range of nortriptyline
75-140
therapeutic range of phenelzine
30-60
therapeutic range of tranylcypromine
20-30
therapeutic range of selegiline
10