Ott Pharmacotherapy of Depression

Question 1

Risk of recurrence of depression

Answer 1

-1 episode: 50-60%
-2 episodes: 70%
-3 episodes: 90%
-Risk becomes lower over time as duration of remission increases
-Persistent mild symptoms during remission is a predictor of recurrence
-Function deteriorates during the episode and goes back to baseline upon remission

Question 2

How is depression diagnosed according to the DSM-5?

Answer 2

At least one of the symptoms must be depressed mood or loss of interest or pleasure in doing things

Question 3

DM-5 diagnostic symptoms of depression

Answer 3

-Sleep (insomnia/hypersomnia)
-Interest decreases
-Guilt/worthlessness
-Energy loss/fatigue
-Concentration difficulties
-Appetite change (increase or decrease)
-Psychomotor agitation/retardation
-Suicidal ideation

Question 4

What is the patient health questionnaire (PHQ-9)?

Answer 4

-Developed for the primary care setting
-Used repeatedly to determine efficacy and treatment
-Scores of 5, 10, 15, and 20 correspond to minimal, mild, moderately sever, and severe depression respectively

Question 5

What is the mood disorder questionnaire (MDQ)?

Answer 5

-Can be used to rule out bipolar disorder
-5 question assessment
-Positive score for bipolar disorder = >7 “yes” responses

Question 6

Goals of depression treatment

Answer 6

-Reduce or eliminate signs and symptoms of depression
-Restore occupational and psychosocial functioning to baseline
-Reduce the risk of relapse and recurrence
-Reduce the risk of harmful consequences (suicidal ideation)

Question 7

What is a boxed warning in all antidepressant medications?

Answer 7

Suicidality for patients 24 years old or younger

Question 8

Citalopram clinical pearls

Answer 8

-Dose-dependent QTc prolongation
-Substrate of 2C19 and 3A4

Question 9

Fluoxetine clinical pearls

Answer 9

-Long half-life (96-144 hours)
-Activating potential
-2D6 inhibitor, 3A4 inhibitor (norfluoxetine)

Question 10

Fluvoxamine clinical pearls

Answer 10

Inhibitor of 1A2 and 2C19

Question 11

Paroxetine clinical pearls

Answer 11

-MUST taper due to anticholinergic effects
-Weight gain, sedation
-Septal wall defect risk to fetus
-Inhibitor of 2D6, 2B6

Question 12

Sertraline clinical pearls

Answer 12

More GI upset than other antidepressants

Question 13

Key adverse effects of SSRIs

Answer 13

-Weight gain (paroxetine)
-Weight loss (fluoxetine)
-Increased bleeding risk (platelet inhibition)
-Hyponatremia (especially in elderly)
-Sexual dysfunction

Question 14

Desvenlafaxine clinical pearls

Answer 14

-Active metabolite of venlafaxine
-Dose-limiting side effect: nausea
-No major CYP interactions

Question 15

Duloxetine clinical pearls

Answer 15

-Nausea
-FDA warning for hepatotoxicity
-Inhibitor of 2D6

Question 16

Levomilnacipran clinical pearls

Answer 16

-MUST adjust in renal impairment or strong 3A4
-Substrate for 3A4

Question 17

Venlafaxine clinical pearls

Answer 17

-Must be more than 150mg/day to have NE effects
-2D6 inhibitor at high doses

Question 18

SNRI adverse effects

Answer 18

-Blood pressure elevation
-Nausea

Question 19

SNRI key points

Answer 19

-Useful in pain syndrome, musculoskeletal pain, fibromyalgia, and neuropathic pain
-Duloxetine requires you to obtain LFTs at baseline and when symptomatic or every 6 months

Question 20

Which TCA is commonly used?

Answer 20

Amitriptyline

Question 21

Side effects of TCAs

Answer 21

-CNS: sedation, reduced seizure threshold, confusion
-Anticholinergic: blurred vision, urinary retention, constipation
-Cardiovascular: orthostatic hypotension, tachycardia
-Other: weight gain, sexual dysfunction
-Fatal in overdose as low as 1000mg due to cardiac arrhythmias or seizures

Question 22

MAOI clinical pearls

Answer 22

-Must have 2 week washout period before switching antidepressants (5 week washout period if switching from fluoxetine)
-All require tyramine diet except selegiline 6mg/24hr patch
-Caution due to hypertensive crisis and serotonin syndrome

Question 23

Bupropion mechanism of action

Answer 23

-Dopamine and norepinephrine reuptake inhibitor
-Stimulating - insomnia and appetite suppression

Question 24

Bupropion clinical pearls

Answer 24

-2D6 inhibitor
-Contraindicated in active seizure disorder and eating disorders
-Can be used in combination with SSRI/SNRI

Question 25

Mirtazapine clinical pearls

Answer 25

-Sedation and increased appetite occur with doses of 15mg/day or less
-Warnings: agranulocytosis, increased cholesterol
-Can be used in combination with SSRI/SNRI

Question 26

Trazodone clinical pearls

Answer 26

-Higher doses needed for depression
-Orthostatic hypotension
-Risk for priapism - medical emergency

Question 27

Vilazodone mechanism of action

Answer 27

-Primarily SSRI, may have some 5HT1a agonism which may provide anxiolytic effects
-Do not use in combination with SSRI/SNRIs

Question 28

Vilazodone clinical pearls

Answer 28

-Take with food
-Causes significant nausea
-Bioavailability increases with food
-Substrate of 3A4

Question 29

Vortioxetine mechanism of action

Answer 29

-SSRI + 5HT1A agonist + 5HT3 antagonist
-Do not use in combination with SSRI/SNRIs

Question 30

Vortioxetine clinical pearls

Answer 30

-Possibly less sexual dysfunction
-Substrate 2D6
-Causes nausea

Question 31

Key points about antidepressant withdrawal syndrome

Answer 31

-Common with ALL antidepressants EXCEPT fluoxetine
-Antidepressants with anticholinergic activity should be tapered no matter what

Question 32

What are the FDA approved augmentation agents?

Answer 32

-Aripiprazole
-Brexpiprazole
-Cariprazine
-Quetiapine

Question 33

Key counseling points for people with depression

Answer 33

-Abrupt discontinuation can lead to antidepressant withdrawal syndrome
-Possible increase in suicidal thinking during the first weeks of therapy