Major Depressive Disorder Flashcards by Kelly Vu

Who is most commonly affected by MDD?

Ages 18-29
Women (2:1 ratio compared to males)

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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

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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

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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

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What mono-therapeutic tx options are considered first line pharmacotherapy for MDD?

SSRI, SNRI, bupropion, mirtazapine

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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

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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

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What are some common ADR of SSRI/SNRIs

Agitation, increased anxiety, nausea, diarrhea, sexual dysfunction, drowsiness, insomnia

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What are some SNRI specific ADRs?

Increased ocular pressure, elevated BP

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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

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What are some DDI with SSRI/SNRI?

CYP2D6/2C19 inhibition
Tamoxifen (big CYP2D6 inducer)
MAOIs (washout required)
Linezolid
NSAIDs
Triptans
Sympathomimetics

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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

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What should be monitored with SSRI/SNRI?

Mood
Adherence
Suicidal Ideation
BP w SNRIs

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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

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What are some clinical pearls w SSRI/SNRI?

Tapering required upon dc

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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

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what is the dose of bupropion?

150-450 mg/day

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What are the ADR of bupropion?

Dry mouth
Insomnia
Nausea
Decreased appetite

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What are some DDI w bupropion?

CYP2B6 inhibition
CBZ
Ritonavir
Linezolid – hypertensive reactions
MAOIs – hypertensive reactions
TCAs – increases seizure activity

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What to monitor w bupropion?

Seizures
BP
Mood
Suicidal Ideation

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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

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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

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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

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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

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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

What are some clinical pearls w mirtazapine?

tapering required

What is Treatment Resistant Depression (TRD)?

Two adequate trials of 4-12 weeks of different antidepressants and lack of full response to each

What are some tx strategies for TRD?

Switch= if all first line agents have not been trialed still considered first line, if they have consider TCAs or MAOIs Augmentation= w lithium, thyroid hormone, or an SGA If patient has shown partial response, “keeping initial med and augmentation is best to ensure clinical effect already gained is not lost”

What agents/drugs/classes can be used for switch strategy in TRD?

SSRIs SNRIs Bupropion Mirtazapine TCAs MAOis

What are some ADR of TCAs?

Sedating Anticholinergic Cardiac conduction abnormalities: cardiotoxicity/prolong qrs/qt intervals Weight Gain

What are some DDI w TCAs?

Hepatic metabolism: 2D6, 2C19 inhibitor CBZ, rifampin Cimetidine, fluoxetine, paroxetine FQ, ziprasidone, quinidine, procainamide, sympathomimetics

What should be monitored w TCAs?

EKG HR BP Electrolytes Mood Suicidal ideation

What are some warnings w TCAs?

BBW: increased risk of suicidal thoughts or behavior in peds and young adults May precipitate mania

What are some clinical pearls of TCAs? Include theraupeutic ranges of specific TCAs mentioned

Tapering required Therapeutic ranges: Amitriptyline: 80-200 ng/ml Doxepin: 50-150 ng/ml Nortriptyline: 50-100 ng/ml

What are some ADR of MAOIs?

Orthostatic HoTN Dry Mouth Constipation Dizziness, HA Sexual dysfunction Weight gain Insomnia Patch = diarrhea

What are some DDI w MAOi?

Atomoxetine, bupropion, CBZ, insulins, linezolid, SSRIs, SNRIs, tramadol, triptans, TCAs, tyramine foods, levodopa, dextromethorphan, sympathomimetics, etc

What should be monitored w MAOIs?

Renal Function BP/HR Mood Suicidal ideation

What are some warnings w MAOIs?

BBW: increased risk of suicidal thoughts or behavior in peds and young adults Can cause HTN crises and/or orthostatic HoTN May precipitate mania

What are some clinical pearls w MAOIs?

Requires low tyramine diet - Tyramine: aged cheeses, alcohol (wine and beer), chocolate, coffee, soy sauce, etc. Requires 14 day washout period from other serotonergic agents* *5 weeks washout for fluoxetine bc of long t1/2

What are some agents/drugs/classes that may be used in augmentation strategy in TRD?

Lithium Thyroid Hormone (T3) SGAs

What are some ADR of Lithium?

Arrhythmias, Drowsiness, Acne, GI effects, Sexual dysfunction, Tremor Polyuria, Weight gain Thirst, diarrhea

What are some DDI w Lithium?

ACEi, caffeine, NSAIDs, thiazides, diuretics, theophylline

What are some warnings w Lithium?

BBW: lithium toxicity Levels of > 1.5 typically is toxic level – sx of toxicity include nausea, tremors, confusion, arrhythmias, overly sedated, slurred speech

What should be monitored w Lithium?

Renal function Lithium levels Thyroid Mood

What are some clinical pearls w Lithium?

Consistent fluid intake Target level: 0.4-0.6

What are some ADR of SGAs?

Constipation, endocrine abnormalities, EPS, drowsiness, QTc prolongation

What are some DDI w SGAs?

DA agonists (ropinirole, pramiprexole, bromocriptine) QTc prolonging agents

What should be monitored w SGAs?

BMI/weight gain A1c/glucose EPS Lipids EKG Mood

What are some warnings w SGAs?

Caution in patients w Parkinson's Disease

What are some clinical pearls w SGAs?

Dosing is lower for MDD dosing compared to dosing for other indications

What are some ADR of Thyroid Hormone?

Diarrhea, HA, nervousness, irritability tachycardia, sweating

What are some DDI of T3?

Separate out from other meds by ~ 4 hours

What should be monitored w T3?

Thyroid function tests, Mood HP/BP Cardiac abnormalities

What are some warnings w T3?

May result in decreased bone mineral density Caution in patients w adrenal insufficiency and/or cardiac issues

What are some clinical pearls of T3?

Administered same time each day

What is the most compelling choice of TRD treatment for younger patients or those who are not great w adherence ?

Fluoxetine (t1/2 24-72 hours)

What is the most compelling choice of TRD treatment for those w concomitant pain conditions?

SNRIs, TCAs

What is the most compelling choice of TRD treatment for those seeking weight loss and/or tobacco use?

Bupropion

What is the most compelling choice of TRD treatment for those who need appetite stimulation and/or need for sleep

Mirtazapine

What is the most compelling choice of TRD treatment for those w concurrent psychiatric disorders?

Lithium, SGAs

What is the most compelling choice of TRD treatment for those w concurrent hypothyroidism?

Liothyronine

What are some general monitoring parameters for MDD?

mood, adherence, suicidal ideation, BMI/weight gain, EPS, A1c/glucose, lipids, EKG, BP, renal function (some of these may be patient-case specific)

What is the criteria for maintenance treatment of MDD?

Those who experience 2+ MDD episodes Family hx of bipolar disorder or MDD Co-occurring SUD or psych disorder

What is the minimum duration of continuation treatment for MDD?

6-9 months after sx remission Same dose as sx remission duration varies between 1 year and lifetime dependent on recurrence and pt preference

What is the adequate length of trials for antidepressant treatment of MDD?

6-12 weeks

When does a patient qualify for TRD?

When they had an adequate trial of two or more antidepressants w no sx remission

What are the different strategies of TRD?

Switch and augmentation

Major Depressive Disorder Flashcards

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