major depressive disorder - dr krysiak

3 hours --> 15 questions

major depressive disorder is a _________ disorder

a. mood

b. thought

a.

list factors associated with increased risk

• female sex

• middle age

• single

• white

• low economic status

• unemployed

• physical disability

• first degree relatives

what is the monoamine hypothesis?

decr. brain levels of NE, 5HT, and DA

which of these is less severe but often longer-lasting form of depression?

a. mania

b. major depression

c. dysthymia

c.

when patients present with depressive symptoms, why do we need to do a complete medical workup and med review?

RULE OUT possible contributing causes to their depressive symptoms

idk if we need to know

what meds can contribute to depressive symptoms

• acne tx

  • isotretinoin

• anticonvulsants

  • levetiracetam

  • topiramate

  • vigabatrin

• antimigraine agents

  • triptans

• CV medications

  • beta blocker

  • clonidine

  • methyldopa

  • reserpine

• hormonal therapy

  • GNRH

  • oral contraceptives

  • steroids

  • tamoxifen

• immunologic agents

  • interferons

• smoking cessation meds

  • varenicline

according to DSM-5, what is required for diagnosis?

5 or more symptoms

at least one of them is :

• depressed mood

• loss of interest or pleasure

how can we remember the DSM-5 diagnostic criteria?

DEPRESSION = SIG E CAPS

S - sleep disorder

I - interest deficit (anhedonia)

G - guilt

E - energy deficit

C - concentration deficit

A - appetite disorder

P - psychomotor retardation or agitation

S - suicidality

checkpoint

which of the following best describes the diagnostic criteria for a major depressive episode according to the DSM-5?

a. at least 3 symptoms present for 1 week

b. at least 5 symptoms present during 2-week period, including depressed mood or loss of interest

c. daily anxiety and insomnia for 3 months

d. depressed mood for at least 6 months

b.

T/F the course of MDD varies significantly from patient to patient - it is uncommon for a pt to experience ONLY a single major depressive episode

TRUE

all antidepressants have a boxed warning for incr. risk of:

a. hepatotoxicity

b. suicidal thinking

c. QT prolongation

d. anticholinergic side effects

b.

what are the risk factors for suicide?

IS PATH WARM

I - ideation

S - substance abuse

P - purposeless

A - anxiety

T - trapped

H - hopelessness

W - withdrawal

A - anger

R - recklessness

M - mood change

depression rating scales are useful for: (SATA)

a. taking subjective info and making it more objective

b. saving time

c. establishing a baseline

d. severely paranoid or agitated patients

a. c.

which of the following is used to assess the symptoms of depression and response?

a. hamilton rating scale for depression (HAM-D)

b. montgomery-asberg depression rating scale (MADRS)

c. beck depression inventory (BDI)

d. quick inventory of depressive symptomatology (QIDS)

a.

which of the following is used to measure the severity of depressive symptoms? (SATA)

a. hamilton rating scale for depression (HAM-D)

b. montgomery-asberg depression rating scale (MADRS)

c. beck depression inventory (BDI)

d. quick inventory of depressive symptomatology (QIDS)

b. c.

which of the following is used to assess the severity of symptoms AND response to treatment?

a. hamilton rating scale for depression (HAM-D)

b. montgomery-asberg depression rating scale (MADRS)

c. beck depression inventory (BDI)

d. quick inventory of depressive symptomatology (QIDS)

d.

what phase is 6-12 weeks with a goal of achieving remission?

a. acute

b. continuation

c. maintenance

a.

what phase is 4-9 months with a goal of eliminating residual symptoms or prevent relapse?

a. acute

b. continuation

c. maintenance

b.

what phase lasts 12-36 months with a goal of preventing recurrence?

a. acute

b. continuation

c. maintenance

c.

who requires lifelong maintenance?

• < 40 y.o. with 2 or more episodes

• any age with 3 or more prior episodes

what principle of antidepressant actions is reducing symptoms by 50%?

a. response

b. remission

c. recovery

d. relapse

e. recurrence

a.

what principle of antidepressant actions is at least 3 weeks of absence of both sad mood and reduced interest, and no more than 3 remaining symptoms of major depressive episode?

a. response

b. remission

c. recovery

d. relapse

e. recurrence

b.

what principle of antidepressant actions is removal of all symptoms for longer than 6-12 months?

a. response

b. remission

c. recovery

d. relapse

e. recurrence

c.

what principle of antidepressant actions is when depression returns within 6 months of remission?

a. response

b. remission

c. recovery

d. relapse

e. recurrence

d.

what principle of antidepressant actions is when depression returns after a patient has recovered?

a. response

b. remission

c. recovery

d. relapse

e. recurrence

e.

what is treatment resistance?

episode that has failed to respond to 2 separate trials of different antidepressants of aequate dose and duration

checkpoint

which treatment phase of depression is focused on preventing recurrence of future depressive episodes?

a. acute phase

b. continuation phase

c. maintenance phase

d. remission phase

c.

list nonpharm therapy options

• electroconvulsive therapy (ECT)

• transcranial magnetic stimulation (TMS)

• vagal nerve stimulation (VNS)

• psychotherapy

• CAM therapy

what is electroconvulsive therapy (ECT)?

course?

CIs and ADRs?

electrodes placed on patient’s scalp, electrical charge stimulates the brain, produces a seizure

course: 6-12 treatments; takes 10-14 days to respond

CIs: MI, bleeding, cerebral lesions/hemorrhage

ADRs: confusion, impaired memory, headache, muscle ache

what is transcranial magnetic stimulation?

course of treatment?

ADRs?

magnetic fields stimulate nerve cells in regions of brain involved in mood regulation and depression

course: 4-6 weeks

ADRs: headache, transient scalp discomfort

what is vagal nerve stimulation (VNS)?

time to response?

ADRs?

adjunctive long-term chronic or recurrent depression lasting for at least 2 years, not responding to at least 4 trials of antidepressants

device surgically implanted under skin of the chest, device stimulates vagus nerve which travels to the brainstem

response: 10 or more weeks

ADRs: voice changes, hoarseness, throat pain, cough, breathing difficulties, chest pain, prickling of skin

for ADRs think of throat stuff

when is psychotherapy indicated?

• monotherapy for mild-moderate acute depression

• combo with pharm therapy for more severe depression

which kind of psychotherapy focuses on the impact of thoughts on emotions and actions?

a. cognitive behavioral therapy (CBT)

b. interpersonal therapy (IPT)

a.

what kind of psychotherapy focuses on building current interpersonal relationships?

a. cognitive behavioral therapy (CBT)

b. interpersonal therapy (IPT)

b.

list CAM options

• St. John’s Wort (Hypericum Perforatum)

• S-adenosyl Methionine (SAMe)

• Folate and L-methylfolate

what CAM therapy may be used as adjunctive support for patients already receiving an antidepressant?

a. St. John’s Wort

b. S-adenosyl Methionine (SAMe)

c. Folate and L-methylfolate

c.

what CAM therapy is available as a medical food and requires a prescription?

a. St. John’s Wort

b. S-adenosyl Methionine (SAMe)

c. Folate

d. L-methylfolate

d.

list the SSRIs

• citalopram (Celexa)

• escitalopram (Lexapro)

• fluoxetine (Prozac)

• fluvoxamine (Luvox)

• paroxetine (Paxil)

• sertraline (Zoloft)

• vilazodone (Viibryd)

• vortioxetine (Trintellix)

idk how important

what SSRI is only FDA approved for OCD and seldom used alone for depression?

a. citalopram

b. fluvoxamine

c. paroxetine

d. vortioxetine

b.

what is the MOA of SSRIs?

inhibit presynaptic serotonin reuptake —> incr. in serotonin overall

with citalopram, which enantiomer is responsible for mild antihistaminic properties (ADRs) and interferes with ability of the other enantiomer to inhibit the serotonin transporter (need higher doses for response)?

a. R

b. S

a.

adults < 60 y.o. should not use citalopram (celexa) at doses greater than _____ because of increased risk of QT prolongation

a. 10 mg

b. 20 mg

c. 40 mg

d. 60 mg

c.

elderly ≥ 60 y.o. should not use citalopram at doses greater than _______

a. 10 mg

b. 20 mg

c. 40 mg

d. 60 mg

b.

escitalopram (Lexapro) is only the ____ enantiomer of citalopram

a. R

b. S

b.

what SSRI also increases NE and DA and may be helpful for patients suffering from hypersomnia and fatigue (it’s a “activating SSRI”)?

a. escitalopram

b. paroxetine

c. fluoxetine

d. sertraline

c.

idk if this is important

what SSRI also comes as a delayed release formulation that is given on a weekly basis and can be used for continuation therapy?

fluoxetine (Prozac Weekly)

what SSRI is preferred for anxiety symptoms becuase it tends to be more calming/sedating (known as a “sedating SSRI”)?

a. escitalopram

b. paroxetine

c. fluoxetine

d. sertraline

b.

what SSRI also inhibits dopamine transport and is commonly given with bupropion (Wellbutrin)?

sertraline (zoloft)

which meds are SSRI and 5-HT1A agonists, and have a faster onset?

which one has lower GI side effects?

vilazodone (viibryd)

vortioxetine (trintellix) —> lower GI side effects

T/F all SSRIs can have withdrawal, but fluoxetine will take longer because of it’s longer half-life

TRUE

what drugs can SSRIs have interactions with, leading to abnormal bleeds?

because SSRIs decr. the efficacy of platelet homeostasis

NSAIDs

antiplatelets

anticoagulants

what SSRIs are potent inhibitors of CYP1A2? (SATA)

a. fluvoxamine

b. fluoxetine

c. paroxetine

d. escitalopram

a.

what SSRIs are potent inhibitors of CYP2D6? (SATA)

a. fluvoxamine

b. fluoxetine

c. paroxetine

d. escitalopram

b. c.

________ carries a black box warning for dose-dependent QTc prolongation and subsequent increased risk of torsades de pointes

citalopram

what is the black boxed warning that ALL SSRIs have?

incr. risk of suicidality in children, adolescents, and young adults age 24 or younger

list common adverse effects of SSRIs

• GI symptoms

  • N/D/anorexia

  • take w/food or HS

• neurologic

  • anxiety

  • insomnia, sedation, HA

• sexual dysfunction

  • decr. libido, delayed ejaculation, anorgasmia, ED

list symptoms of withdrawal syndrome with SSRIs hours after interruption

• dizziness

• vertigo

• nausea

• fatigue

• HA

• anxiety

• agitation

• insomnia

• irritability

what SSRI has less withdrawal syndrome?

which has more?

less: fluoxetine

more: paroxetine

_______ is a rare but potentially fatal side effect of SSRIs, more common with older age, females, and use with diuretics

hyponatremia

after initiating SSRIs or SNRIs, assessment should be conducted _________ for the first 8 weeks

weekly to biweekly

list the SNRIs

• venlafaxine (Effexor)

• desvenlafaxine (Pristiq)

• duloxetine (Cymbalta)

• levomilnacipran (Fetzima)

what are the “two and a half” mechanisms of SNRIs?

1. boosting 5HT throughout the brain

2. boosting NE throughout the brain

3. boosting DA in the prefrontal cortex

   1. NE reuptake inhibition boosts DA in the prefrontal cortex

what is the active metabolite of venlafaxine?

what does it have greater affinity for (compared to venlafaxine)?

active metabolite: desvenlafaxine (Pristiq)

greater affinity for NE receptor

what SNRI may cause dose-related increase in blood pressure?

venlafaxine (Effexor)

what is duloxetine (Cymbalta) FDA approved for?

who is it CI in?

• approved for:

  • MDD

  • diabetic peripheral neuropathy

  • fibromyalgia

  • chronic musculoskeletal pain

• CI in hepatic insufficiency (CrCl < 30 mL/min)

why does duloxetine (Cymbalta) have a higher incidence of dry mouth and constipation compared to venlafaxine (Effexor)?

antagonizes M1 muscarinic receptors

what does levomilnacipran (Fetzima) have more affinity for?

a. NE transporters

b. 5HT transporters

a.

what SNRIs have CYP interactions?

duloxetine and venlafaxine: inhibitor and substrate of 2D6

levomilnacipran: substrate of 3A4

who should we use SNRIs cautiously with?

history of HTN and narrow angle glaucoma

who do we avoid using duloxetine in?

history of hepatic impairment or heavy alcohol use

(risk of urinary retention)

what SNRI has a risk of seizures and urinary retention?

levomilnacipran

list the TCAs

• tertiary amines

  • amitriptyline (Elavil)

  • clomipramine (Anafranil)

  • doxepin (Sinequan)

  • imipramine (Tofranil)

• secondary amines

  • desipramine (Norpramin)

  • nortriptyline (Pamelor)

tertiary amines have greater affinity for ______; secondary amines have greater affinity for _______

a. tertiary: NE; secondary: 5HT

b. tertiary: 5HT; secondary: NE

b.

idk how important

what is the active metabolite of amitriptyline? imipramine?

amitriptyline: nortriptyline

imipramine: desipramine

T/F all TCAs are CYP3A4 substrates

FALSE — CYP2D6

T/F TCAs are lethal in overdose

TRUE

list warnings of TCAs

• lethal in overdose

• caution with CV disease

• avoid alcohol

• lower seizure threshold

• anticholinergic effects

  • caution in hx of glaucoma

• photosensitization

which are better tolerated (less sedative and anticholinergic)?

a. secondary amines

b. tertiary amines

a.

what TCA can cause urine discoloration (blue/green)?

amitriptyline

list sx of TCA overdose

• severe hypotension

• confusion

• hyperthermia

• urinary retention

• CNS depression

• arrhythmias

• seizures

• coma

T/F therapeutic effect of TCAs should be based solely on plasma levels

FALSE — should NOT be solely based on plasma levels

but you can draw them at steady state —> min. 1 week

list the MAOIs

• phenelzine (Nardil)

• selegiline transdermal (Emsam)

• tranylcypromine (Parnate)

• isocarboxazid (Marplan)

idk if important

distinguish between MAO-A and MAO-B

• MAO-A

  • metabolizes 5HT and NE

  • located in the intestinal epithelium

  • responsible for breakdown of tyramine and prevents its reabsorption

• MAO-B

  • metabolizes trace enzymes

• both A and B

  • located in the brain

  • metabolize DA and tyramine

what is the biggest barrier to using MAOIs?

interactions!!

can’t eat a bunch of tyramine —> it will incr. BP

which dose of selegiline patch (Emsam) requires dietary caution? why?

a. low doses —> 6 mg/24 hours

b. high doses —> 9 mg/24 hours

b.

patch avoids first pass thru liver —> does NOT inhibit gut MAO-A

what interacts with MAOIs because it can imitate the effects of NE and lead to hypertensive crisis?

sympathomimetics

OTC vasoconstrictors: phenylephrine, pseudoephedrine, ephedrine

list the triazolopyridines

• trazodone (Desyrel)

• nefazodone (Serzone)

list triazolopyridines interactions and warnings/precautions

• interactions

  • serotonin syndrome

  • nefazodone: CYP3A4 inhibitor

  • trazodone: CYP3A4 substrate

• warnings/precautions

  • BBW: incr. risk of suicidality

  • nefazodone BBW: life-threatening liver failure

  • orthostatic hypotension

  • incr. QTc prolongation

  • risk of priapism

what do we need to monitor with nefazodone (serzone)? when do we discontinue?

LFTs at baseline and every 3-6 months as indicated

discontinue: AST or ALT reach 3 times or greater the ULN

what drug has NO serotonergic effects, is generally activating (good for pts with excessive sedation), does NOT cause sexual dysfunction, and is good for pts with “dopamine deficiency syndrome”?

bupropion (Wellbutrin)

list interactions of bupropion (Wellbutrin)

• substrate of CYP2B6

• inhibits CYP2D6

  • incr. conc. of metoprolol and TCAs

• risk of seizures incr. (when on other meds that lower threshold)

• hypertensive crisis (when combined with MAOIs)

how can you minimize the risk of seizures with bupropion?

• avoid use in susceptible patients

• don’t give more than 150 mg/dose

• avoid rapid titration

what is one of the only antidepressants that increases 5HT release and does NOT cause sexual dysfunction?

also has reduced nausea and GI problems

mirtazapine (Remeron)

list ADRs of mirtazapine (remeron)

what should we monitor?

• ADRs

  • sedation

  • weight gain

  • hypertriglyceridemia

  • dry mouth

• monitoring

  • weight

  • triglycerides

checkpoint

which of the following antidepressants is LEAST likely to cause sexual dysfunction and is considered activating?

a. paroxetine

b. fluoxetine

c. bupropion

d. citalopram

c.

checkpoint

which of the following side effects is most closely associated with mirtazapine?

a. insomnia and GI upset

b. weight loss and diarrhea

c. sexual dysfunction and tremor

d. weight gain and sedation

d.

checkpoint

which of the following medications is associated with a dose-dependent risk of QT prolongation and is limited to a maximum of 40 mg/day in adults < 60 years old?

a. sertraline

b. citalopram

c. fluoxetine

d. paroxetine

b.

how long do we need to wait after discontinuing an MAOI before initiating a serotonergic agent?

2 weeks

how long do we need to wait after discontinuing an SSRI to initiate an MAOI?

2-4 weeks

how long do we need to wait after discontinuing fluoxetine to initiate an MAOI?

5 weeks