Major Depressive Disorder Flashcards
Shahid
Who is most commonly affected by MDD?
Ages 18-29
Women (2:1 ratio compared to males)
Epidemiology of MDD
high prevalent (one of the most common psychiatric disorders)
~7% of Americans affected annually (20+ million)
remission rate diminish w each trial
What is the pathophysiology of MDD?
Not clearly defined
Previous trials suggest a disturbance in CNS serotonin (5HT) activity as an important factor
Multifactorial w both genetic and environmental factors
What is the DSM5 criteria of a depressive episode ?
5+ of sx (listed below) during same 2 week period
Causes significant distress of functional impairment
Not attributable to physiological effects of substance or other medical conditions
Sx examples: insomnia/hypersomnia, diminished interest/pleasure, guilt/worthlessness, fatigue/loss of energy, low concentration, loss of appetite/weight loss/weight gain, psychomotor, suicidal, depressed mood
What mono-therapeutic tx options are considered first line pharmacotherapy for MDD?
SSRI, SNRI, bupropion, mirtazapine
What is the MOA of SSRIs?
Inhibits presynaptic reuptake of 5HT at the 5HT transporter, thus increasing 5HT at the postsynaptic membrane in the serotonergic synapse
What is the MOA of SNRIs?
Inhibits reuptake of 5HT and NE into neurons preventing chemical messengers from being taken back into brain cells that released them thus increasing levels in the brain
What are some common ADR of SSRI/SNRIs
Agitation, increased anxiety, nausea, diarrhea, sexual dysfunction, drowsiness, insomnia
What are some SNRI specific ADRs?
Increased ocular pressure, elevated BP
What are some SSRI agent specific ADRs?
Citalopram: risk of prolonged QTc interval (at normal doses)
Escitalopram: risk of prolonged QTc interval (at high supratherapeutic doses)
(citalopram has a higher incidence of QTc interval prolongation)
Fluoxetine: 24-72 hr t1/2, most activating
Paroxetine: greater risk of anticholinergic effects, most sedating
Sertraline: most benign SE profile
What are some DDI with SSRI/SNRI?
CYP2D6/2C19 inhibition
Tamoxifen (big CYP2D6 inducer)
MAOIs (washout required)
Linezolid
NSAIDs
Triptans
Sympathomimetics
What is the washout period required when switching to or from MAOIs from SSRI/SNRIs?
and what is the important note w this?
14 days
Note: not very commonly that you see this, can greatly increase risk of toxicity or hypertensive emergency
Nonselective MAOIs and linezolid do not need washout period
What should be monitored with SSRI/SNRI?
Mood
Adherence
Suicidal Ideation
BP w SNRIs
What are some warnings with SSRI/SNRI?
BBW: increased risk of suicidal thoughts or behaviors in peds and young adults
Serotonin syndrome
Increased bleeding risk
Can precipitate mania
What are some clinical pearls w SSRI/SNRI?
Tapering required upon dc
What is the MOA of bupropion?
Not fully understood, weak inhibitor of neuronal uptake of NE and DA, does not inhibit MAO or reuptake of NE and DA, does not inhibit MAO or reuptake of 5HT, metabolite inhibits reuptake of NE
what is the dose of bupropion?
150-450 mg/day
What are the ADR of bupropion?
Dry mouth
Insomnia
Nausea
Decreased appetite
What are some DDI w bupropion?
CYP2B6 inhibition
CBZ
Ritonavir
Linezolid – hypertensive reactions
MAOIs – hypertensive reactions
TCAs – increases seizure activity
What to monitor w bupropion?
Seizures
BP
Mood
Suicidal Ideation
What are some warnings w bupropion?
BBW: increased risk of suicidal thoughts or behavior in peds and young adults
Increases risk of seizures
Can precipitate mania
What are some clinical pearls w bupropion?
Tapering is not required but preferred if possible
Avoid alcohol
Myth buster: people assume because bupropion can affect seizure threshold that this must be tapered however in theory this could actually be increasing threshold upon discontinuation, try not to d/c suddenly as it may lead to untreated depression which can be detrimental in and of itself
What is the MOA of mirtazapine?
Central presynaptic alpha2-adrenergic antagonist effects resulting in increased release in NE and5HT, potent antagonist of 5HT2, 5HT3, H1 receptors
What is the dosing for mirtazapine?
15-45 mg/day
higher doses for mood
The higher into the dose, you target more mood than sleep
What are the ADR of mirtazapine?
Dry Mouth
Drowsiness
Constipation
Increased appetite
(anticholinergic effects)
What are some DDI w mirtazapine?
CYP1A2/2D6/3A4 inhibition
MAOIs
Linezolid
Clonidine
Triptans
What should be monitored w mirtazapine?
mood
suicidal ideation
What are some warnings w mirtazapine?
BBW: increased risk of suicidal thoughts or behavior in peds and young adults
May overly sedate