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PMHNP > Antidepressants and Depression > Flashcards

Antidepressants and Depression Flashcards

1
Q

epidemiology

A

5% adults with depression

leading cause of disability worldwide

US lifetime prevalence 20%

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2
Q

risk factors

A

2:1 F:M
native
1st deg relative

middle aged, stress, recent loss

chronic medical illness

personal hx of MDD and/or SUD

previous major depressive episodes

risk inc with number of episodes

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3
Q

Pathophysiology of MDD Neuroanatomical abnormalities

A

Multiple structures

overactive amygdala

overactive subgenual anterior cingulated cortex

decreased dorsolateral PFC activity

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4
Q

Pathophysiology of MDD Neurotransmitter involvement

A

Monoamine hypothesis
o 1950s development with noted dec of 5HT, NE, DA and noted MAOI and TPA improvement but missed delayed onset effect on mood and its relation to synaptic changes

Dysregulation hypothesis
o Accounts for delay in onset of antidepressant action and shows more than inc or dec in concentration

Chronic stress model
o Effect on hypothalamic (HPA) leads to secretion of glucocorticoid and cortisol which leads to neurogenesis in the hippocampus

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5
Q

DSM MDD

A

1 or more major depressive episodes with no hx of manic or mixed mood episodes
AND
5 or more of sx nearly every day for at least 2 wks

Depressed mood most of the time and on most days

Decreased interest or pleasure in daily activities most of the time and on most days

Significant changes in weight or appetite

Significant changes in sleep

Psychomotor agitation or retardation which is observable by others

Fatigue or decreased energy

Feelings of worthlessness or inappropriate guilt

Decreased concentration or difficulty making decisions

Recurrent thoughts of death, suicidal ideation without a specific plan, specific plan for committing suicide, or a suicide attempt

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6
Q

Clinical status

severity, psychotic features?

A

severity
- mild: 5 or 6 sx and minimal functional impairment
-severe: nearly all sx and significant impairment of functioning

can be present with psychotic features

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7
Q

clinical status

remission, chronic definition

A

remission: absence of significant sx for at least 2 months

chronic MDD: full criteria for major depressive episode for a minimum of 2 years

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8
Q

descriptive specifiers for MDD

A

Anxious distress
* Inc SI and worse outcome
* Tension, fear restless

Mixed features
* Mania but not criteria for specific but is RF for BP

Catatonic features
* Immobility etc

Melancholic features
* Severe depression
* Lack of stimuli

Atypical features
* Mood reactivity issue
* Weight, sleep

Peripartum onset
* During or after

Seasonal pattern

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9
Q

treatment by generation/class

A

1st gen
- TCA
-MAOI

2nd gen
-SSRI
-SNRI
-Buproprion
-Mirtazapine
- Trazodone

Newer
-Vilazodone
-Vortioxetine

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10
Q

SSRI MOA

A

inhibit presynaptic serotonin reuptake by interfering with 5HT transporter

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11
Q

SSRI side effects

A

Headache
wt gain
GI
sex
agitation/anxiety (when starting)

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12
Q

SSRI rx and initial dosing

A

Citalopram (Celexa ®): initial dose 20 mg PO once daily
- note QT prolong is dose dependent

Escitalopram (Lexapro ®): initial dose 10 mg PO once daily

Sertraline (Zoloft ®): initial dose 25-50 mg PO once daily
- QT

Paroxetine (Paxil ®): initial dose 20 mg PO once daily
- short half life
- higher risk discontinuation syndrome

Fluoxetine (Prozac ®)* : initial dose 20 mg PO once daily
- long half life
- QT

Fluvoxamine (Luvox ®) : initial 50 mg PO once daily

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13
Q

SNRI MOA

A

5HT receptors too BUT also inhibit NE reuptake (both by inhibition of transporters)

That leads to inc in 5HT and NE in the cleft

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14
Q

SNRI side effects

A

Same as SSRI
AND

hypertension
++ nausea/diarrhea
sweating
dry mouth
dizziness
fatigue

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15
Q

SNRI rx and initial dose

A

Duloxetine (Cymbalta ®): initial dose 40-60 mg PO once daily
- pain
-inhibits NE more than venlafaxine but that causes more dry mouth and constipation

Venlafaxine (Effexor ®): initial dose 37.5-75 mg PO once daily
- pain
- may inc cholestrol

Desvenlafaxine (Pristiq ®): initial dose 50 mg PO once daily

Levomilnacipran (Fetzima ®): initial dose 20 mg PO once daily
-recent approval

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16
Q

TCA MOA

A

Inhibit presynaptic 5HT and NE reuptake by inhibition of transporters which leads to inc in 5HT and NE in cleft

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17
Q

TCA AE

A

o Tertiary amine
More sedation and anticholinergic AE
5HT

o Secondary amine
More CV effect
Better tolerated
NE

overdose potential and cardiac effects

anticholinergic AE: confusion, constipation, wt gain, sedation

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18
Q

Tertiary amines (5HT) rx and initial dose

A

Amitriptyline (Elavil ®): initial dose 25-50 mg PO once daily

Imipramine (Tofranil ®): initial dose 25-50 mg PO once daily

Clomipramine (Anafranil ®): initial dose 25-50 mg PO once daily

Doxepin (Silenor ®): initial dose 25-50 mg PO once daily

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19
Q

Secondary amines (NE) rx and initial dose

A

Nortriptyline (Pamelor ®): initial dose 25 mg PO once daily

Desipramine (Norpramin ®): initial dose 25-50 mg PO once daily

Amoxapine (Asendin®): initial dose 25-50 mg PO 1-3 times daily

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20
Q

MAOI MOA

A

Irreversibly inhibit monoamine oxidase preventing metabolism of NE, 5HT, and dopamine

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21
Q

MAOI 2 types

A

MAO-A
MAO-B

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22
Q

MAOI drug interactions

A

amphetamines

carbamazepine

decongestants

ephedrine

dextromethorphan

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23
Q

MAOI AE

A

Cardiovascular side effects
–require dietary restrictions (aged meat/cheese, soy, or tyramine containing foods)
–Hypertensive crisis

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24
Q

MAOI rx and initial dose

A

Tranylcypromine (Parnate ®): initial dose 10-30 mg PO in divided doses

Phenelzine (Nardil ®): initial dose 15 mg PO 1-3 times daily

Isocarboxazid (Marplan ®): initial dose 10 mg PO twice daily

Selegiline transdermal (Emsam ®): initial dose 6 mg/24-hour patch once daily

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25
Q

Bupropion MOA

A

Inhibits DA and NE transporters, increasing dopamine and norepinephrine concentrations in the synapse

26
Q

Bupropion initial dose

A

IR 100 mg PO twice daily

12-hour ER 150 mg PO once daily

24-hour ER 150 mg PO once daily

27
Q

Bupropion AE

A

Insomnia (11-40%)

Activation/anxiety (2-30%)

Seizure (0.1% at approved doses), may be no higher than other antidepressants and close to incidence in general population.
–Highly dose related at > 600mg (2%)
–Consider risk of seizures in populations with substance use disorder, and history of head trauma

Hypertension (2.5-4.3%)

Less sexual dysfunction and weight gain

28
Q

Mirtazapine (remeron) MOA

A

increases synaptic concentration of serotonin and norepinephrine through presynaptic alpha 2 antagonism

Also, a 5HT2 and 5HT3 antagonist and histamine-1 antagonist

29
Q

Mirtazapine (remeron) initial dose

A

15mg PO qd

30
Q

Mirtazapine (remeron) AE

A

Sedation (advise patient to take at bedtime)

Increased appetite
–may lead to weight gain

Hypertriglyceridemia

Liver toxicity and agranulocytosis (rare)

31
Q

Trazodone and Nefazodone MOA

A

weak inhibition of presynaptic serotonin and norepinephrine reuptake (for nefazodone), 5HT2a antagonist, weak alpha-1 antagonist, and histamine-1 antagonist (trazodone > nefazodone)

32
Q

Trazodone and Nefazodone initial dose

A

Trazodone: IR 50 mg PO twice daily or ER 150 mg PO once daily

Nefazodone: 100 mg PO twice daily

33
Q

Trazodone and Nefazodone AE

A

Nefazodone
-Nausea (32%), headache (26%), dry mouth (25%)
-Hepatic failure (routine liver function test monitoring required)

Trazodone
-Somnolence, nausea (21%), dry mouth (14-33%), and dizziness (25%)

34
Q

Vortioxetine (trintellix) MOA

A

Inhibition of 5HT reuptake

Serotonin 5HT3, 5HT1D, 5HT7 antagonism

Serotonin 5HT1a agonist

35
Q

Vortioxetine (trintellix) initial dose

A

5-10mg PO qd

36
Q

Vortioxetine (trintellix) AE

A

GI

Dry mouth

Sex dysfunction

37
Q

Vilazodone (viibryd) MOA

A

inhibition of presynaptic 5-HT reuptake by inhibition of the 5-HT transporter
–leads to increased 5-HT in synaptic cleft

Also, a 5-HT1a partial agonist

May have some affinity for NE and DA transporters

38
Q

Vilazodone (viibryd) initial dose

A

10mg PO qd

39
Q

Vilazodone (viibryd) AE

A

GI
insomnia

40
Q

MDD pos and neg for sedation

A

pos
- paroxetine
-mirtazapine
- trazodone

neg
-Buproprion
-fluoxetine
-sertraline

41
Q

MDD pos and neg for weight gain

A

pos
- paroxetine
-mirtazapine

neg
-Buproprion
-Duloxetine
-fluoxetine

42
Q

MDD pos and neg for bleeding risk

A

pos
-SSRI

neg
-Bupropion
-mirtazapine

43
Q

MDD pos and neg for sex dysfunction

A

pos
- paroxetine
-venlafaxine
-sertraline

neg
-Buproprion
-mirtazapine
-vortioxetine

44
Q

MDD pos and neg for hypertension

A

pos
-bupropion
-venlafaxine

neg
-SSRI

45
Q

discontinuation syndrome

A

Flu like symptoms that occur after abrupt discontinuation of SSRI/SNRI, taper slow (except fluoxetine)

46
Q

Star-D for depression

A
  1. Citalopram
  2. Switch
    - Sertraline
    - Bupropion
    -Venlafaxine
    -CBT
  3. Augment
    -Bupropion
    -Buspirone
    -CBT

2a
- venlafaxine
-Bupropion

  1. Switch
    -mirtazapine
    -nortyptiline
  2. Augment
    - Lithium
    -Thyroid hormone

-largest and longest study
-compared acute and long term tx outcomes associated with steps

cumulative remission rate: 67%

47
Q

APA 1st line and 2nd line

A

mild-mod
-psychotherapy +/- SSRI, SNRI, mirtaz, or bupro

mod-severe
- pharmacotherapy +/- psychotherapy

Psychotic features
- antidepressant + Antipsychotic
- ECT- severe depression

2nd
- switch but keep mono
- augment with antidepressant with diff mechanism
- quetapine
-psychotherapy

48
Q

NICE guideline 1st

A

mild
-psychotherapy

mod-sev
-psych +/- pharma

severe
-ECT

49
Q

CANMAT 1st line

A

1st
-SSRI, SNRI, and other newer agents based on safety and tolerability over TCAs or MAOIs

Psychotic features
-Antidepressant + Antipsychotic

50
Q

CANMAT 1st line adjunctive

A

1st
-Aripiprazole, quetiapine, risperidone

51
Q

Approach to tx of MDD 1-4 wks

A

Response
- full- maintain tx
-partial/none–assess adherence, inc as tolerated

if 50% reduction in sx cont at optimal dose and monitor at 6, 8, 12 wks

52
Q

Approach to tx of MDD 4-8 wks

A

Response
- full- maintain tx
-partial/none–inc as tolerated, switch if no response at 8 wks, augment

53
Q

MDD dx improvement: sleep

A

trazodone

mirtazapine

paroxetine

54
Q

MDD dx improvement: concentration

A

bupropion

duloxetine

fluoxetine

55
Q

MDD dx improvement: anxiety

A

sertraline

fluvoxamine

paroxetine

SNRI

56
Q

MDD dx improvement: pain

A

SNRI

57
Q

Rx choice based on

A

Past response (or family member response) to medication

Other psychiatric co-morbidities

Potential for drug interactions

Safety

Patient preference

Cost

58
Q

patient education- counseling

A

When to start working
What to expect
Adverse side effects
Discontinuation syndrome

59
Q

patient education- duration of therapy

A

1st episode – at least 6 months
2nd episode – at least 1 year
3rd episode – lifetime

60
Q

new rx- Esketamine (spravato)

A
  • Adjunct PO
  • Black box noted
  • For tx resistant
  • REMS
  • Expensive
61
Q

new rx- brexanolone (zulresso)

A
  • GABA- A
  • Postpartum
  • Infusion in facility
  • Black box
  • REMS
  • Very expensive

PMHNP (24 decks)

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