Major Depressive Disorders Flashcards
What antidepressants are first generation agents?
-tricyclic antidepressants (TCAs)
-monoamine oxidase inhibitors (MAOIs)
What antidepressants are second generation agents?
-selective serotonin reuptake inhibitors (SSRIs)
-serotonin norepinephrine reuptake inhibitors (SNRIs)
What is the mechanism of action of SSRIs?
inhibit presynaptic serotonin reuptake = increased serotonin in the synaptic cleft= more serotonin available (may also increase norepinephrine and dopamine at higher doses)
What is the general dosing of SSRIs?
once daily at bedtime or morning
What is the place in therapy of SSRIs?
first line due to equivalent efficacy and better tolerability than 1st gen agents
What is the dosing of Fluoxetine?
-initial= 10mg/day
-maintenance= 20-40mg
-max dose= 80mg/day
What is the t1/2 of Fluoxetine?
up to 6 days with chronic use
What is the dosing of Paroxetine?
-immediate release= 10mg initially, max dose 50mg/day
-controlled release= 25mg/day, increased by 12.5mg weekly, max dose 62.5mg/day
What may occur with missed doses of Paroxetine?
increased withdrawal effects due to shorter t1/2
What are the significant side effects of Paroxetine?
-anticholinergic effects
-weight gain
-sexual dysfunction
-sedation
-tremor
What is the dosing of Sertraline?
-initial= 12.5-25 mg/day
-maintenance= 100 mg/day
-max= 200 mg/day
What are the significant side effects of Sertraline?
GI side effects initially
What is the contraindications of Sertraline?
severe liver impairment
What is the dosing of Citalopram?
-initial= 10mg daily
-maintenance= 20mg daily
-max= 40mg daily
What are the risks associated with Citalopram?
doses > 40 mg/day not recommended due to prolonged QTc/torsades risk
What is the dosing of Escitalopram?
-initial= 10mg daily
-max= 20mg daily
What are the pros of Escitalopram?
minimal drug/CYP interactions compared to SSRIs
What is the dosing of Fluvoxamine?
-initial= 50mg at bedtime
-increase by 50mg weekly, max dose= 300mg/day
->100mg daily should be dosed BID
What are the significant side effects of Fluvoxamine?
sedation
What is the indication of Fluvoxamine?
obsessive compulsive disorder (off label for depression)
What are the additional benefits of SNRIs besides MDD?
-pain syndromes
-vasomotor symptoms of menopause
What is the dosing of Venlafaxine?
extended release preferred
-initial= 37.5-75mg daily
-increase by 37.5-75mg weekly
-usual dose range 75-225mg/day
What is the neurotransmitter activity of Venlafaxine?
- <150mg/day= primary serotonin
- > 150mg/day= norepinephrine and serotonin
What are the cautions of Venlafaxine?
-hypertension (dose related, OK if HTN is controlled)
-increased withdrawal effects in abrupt continuation (IR>ER)
-dose reduction in renal impairment
What is the dosing of Duloxetine?
-initial= 20mg/day
-usual dose= 20-60mg/ day, may BID
-max= 120mg/day
What are the concerns with Duloxetine?
-avoid in renal (CrCl < 30mL/min) and hepatic dysfunction
-slightly more anticholinergic than venlafaxine
-indicated for use in various pain syndromes
-contraindicated in closed angle glaucoma
What is the MOA of Bupropion?
dopamine and norepinephrine uptake inhibitor
What are the indications of Bupropion?
-vegetative symptoms/melancholic depression
-hypersomnia
-inattention
-sexual dysfunction or weight gain due to SSRIs
When would you avoid using Bupropion?
very activating
-avoid dosing after 2PM
-avoid in uncontrolled anxiety
What are the contraindications of Bupropion?
history of seizure!
-use caution with concomitant use with drugs that lower seizure threshold and in pt that are withdrawing from benzos and alcohol
eating disorders!
-electrolyte abnormalities may lead to seizures
What are the side effects of Mirtazapine?
dose related side effects!
-lower doses= sedation and weight gain
-higher doses= more activating, less sedation and weight gain
What may be the uses of Mirtazapine?
-pt with insomnia
-malnourished pt
What is the use of Trazodone?
not effective in depression, lower doses used for insomnia
What are the disadvantages of Vortioxetine?
-withdrawal symptoms possible over 15 mg/day
-sexual dysfunction
-CYP2D6 substrate (dose adjustment needed)
What is the advantage of Vilazodone?
less sexual dysfunction due to less potent serotonin reuptake
What is the caution associated with Nefazodone?
hepatotoxicity
What is the risk of using Gepirone?
QTc prolongation and must decrease dose in hepatic impairment
What is the MOA of Tricyclic Antidepressants (TCAs)?
block serotonin and norepinephrine reuptake
What is the use of Tricyclic Antidepressants (TCAs)?
adjunct or last line therapy, may be useful in patients with concomitant conditions, such as: pain (neuropathies or migraines), nocturnal enuresis, or OCD
What are the side effects of Tricyclic Antidepressants (TCA)?
-antihistamine= sedation and weight gain
-antimuscarinic= anticholinergic SE
-alpha 1 agonist= hypotension and dizziness
-voltage gated Na+ channel blocker= antiarrhythmic
In what patient populations should Tricyclic Antidepressants (TCAs) be avoided?
-actively suicidal pt or history of suicide attempt
-elderly
-significant cardiac comorbidity
What may occur with Tricyclic Antidepressant (TCA) toxicity?
LD50= 35mg/kg
heart block, seizures, or sudden cardiac death
What is the use of Monoamine Oxidase Inhibitors (MAOI)?
rarely used due to SE, drug interactions, and dietary restrictions
What are the drug interactions of Monoamine Oxidase Inhibitors (MAOI)?
-sympathomimetics (stimulants, phenylephrine)
-other serotonin agents REQUIRED 14 day washout
What are the adverse effects of Monoamine Oxidase Inhibitors (MAOIs)?
-orthostatic hypotension
-sedation
-weight gain
-anticholinergic SE
-sexual dysfunction
What are the dietary restrictions when using Monoamine Oxidase Inhibitors (MAOI)?
foods high in tyramine
-smoked/aged meats
-aged cheeses
-anything fermented
What antidepressant class is the worst offender of QT prolongation?
TCAs
What are the highest risk antidepressants for QT prolongation?
-citalopram at doses > 40mg/day
-escitalopram is a high risk SSRI
-venlafaxine is highest risk SNRI
Which antidepressants are considered safe for QT prolongation?
-sertraline
-bupropion
What is the correlation between antidepressant and NSAID use?
do not use NSAIDs for pain but acetaminophen because of increased bleed risk
What is the management protocol for Serotonin Syndrome?
-discontinue offending agents
-supportive care for mild case (most cases): rehydration, benzos for agitation/sedation, cooling, antihypertensives
-in severe cases: serotonin antagonists
What are the symptoms of Antidepressant Withdrawal?
VIVID
-Vivid dreams
-Insomnia
-Vomiting
-Irritability
-Dizziness
-others: brain zaps, body aches, fever, worsening mood
What is the use of Lithium in major depressive disorder?
adjunct agent with quick therapeutic response (48-72h) that can be used to treat acute suicide ideation
What are the cautions of Lithium?
-tolerability= tremors, dermatologic SE, sedation
-renal impairment
What are the atypical antipsychotics used in major depressive disorder?
do not use as monotherapy
aripiprazole, brexpiprazole, quetiapine, and cariprazine (FDA approved)
How is treatment resistant depression defined?
failure of 2+ adequate trials of antidepressant therapy
What are the treatment options of treatment resistant depression?
-electroconvulsive therapy (ECT)
-transcranial magnetic stimulation (TMS)
-Esketamine
What is the MOA od Esketamine?
NMDA receptor antagonist= increased glutamate release
What are the Black Box Warning of Esketamine?
REM program
-sedation
-dissociation
-abuse and misuse
-suicidal behavior
What are the antidepressants preferred in pregnancy?
sertraline, fluoxetine, escitalopram
What antidepressants are preferred in lactation?
sertraline and paroxetine
What antidepressants should not be used in pregnancy?
paroxetine
What antidepressant should not be used in lactation?
fluoxetine
What is the risk of using antidepressants in pregnancy?
poor neonatal adaptation syndrome due to newborn withdrawal, symptoms= irritability, difficulty feeding, sleep disturbances
What is the use of Brexanolone?
post partum depression but is 60h infusion and REM program
What is the use of Zuranolone?
post partum depression
What antidepressants may be used in children/adolescents?
fluoxetine (8+ years old) or escitalopram (12+ years old)
What are first line therapy antidepressants for geriatric pts?
SSRIs (avoid MAOIs and TCAs)
