Depression

Question 1

What are the major pathophysiological causes of depression?

Answer 1

The Monoamine hypothesis
Post-synaptic changes - downregulation of post-synaptic Beta/5HT1A receptors
Dysregulation hypothesis - homeostatic mechanisms fail to regulate neurotransmitter systems.
Allopreganolone provides neuroprotection
Neurotrophic changes - BDNF is the primary mediator for neuronal plasticity and chronic stress (increase in cortisol) reduce BDNF
Chronic inflammation - Decrease in BDNF

Question 2

Name 3 drugs that can cause MDD?

Answer 2

Isotretinoin, Methyldopa, B-Blockers, Varenicline

Question 3

What is the DSM-V diagnostic criteria for MDD?

Answer 3

SAGE CAPS

Question 4

What are the main treatment goals for MDD?

Answer 4

Complete symptom relief (achieve remission)
Prevention of further episodes (prevent relapse/recurrence)

Question 5

What are the 3 treatment phases?

Answer 5

Acute (6-12 weeks) relieve symptoms/achieve remission
Continution (4-9 months) prevent relapse
Maintainance (12-36 months) prevent recurrence

Question 6

What are common adverse effects of SSRIs?

Answer 6

GIT - Nausea, Vomiting
Anxiety
Headache
Change in sleep patterns
Sexual dysfunction

Question 7

What about adverse effects for specific SSRIs

Answer 7

Discontinuation syndrome - abrupt cessation
Paroxetine - anticholinergic and antihistamine
Citalo/Escitalopram can cause QT prolongation.

Question 8

What drugs are inhibit CYP450 enzyme

Answer 8

Fluoxetine, Paroxetine

Question 9

What are examples of SNRIs?

Answer 9

TCAs, Amitriptyline, Imipramine, Despiramine, Doxepin

Question 10

What are adverse effects of SNRIs?

Answer 10

H1 - sedation, weight gain
Alpha - postural hypotension
M - anticholinergic SEs (urinary retention, constipation, dry mouth)

Question 11

What are other noteworthy adverse effects in suspectible patients taking SNRIs

Answer 11

Class IA antiarrhthymic effects
Can cause heart block
Overdose: severe arrhythmias

Question 12

What are examples of newer generation SNRIs?

Answer 12

Venlafaxine, Desvenlafaxine, and Duloxetine

Question 13

What is special about binding for Newer SNRIs?

Answer 13

Duloxetine: Blocks 5HT and NE reuptake at any dose
Venlafaxine and Desvenlafaxine: Low dose: Inhibits 5-HT reuptake
Higher dose: inhibits NA reuptake
Reboxetine: Potent NA reuptake

Question 14

What about their antagonism profile?

Answer 14

They have a very low antagonism to M1, H1 and alpha 1.

Question 15

What is the MOA of vortioxetine?

Answer 15

It is an SSRI and agonist at 5HT1A and 5HT1B receptors. And an antagonist at 5HT1D and 5HT7 (improves cognition)

Question 16

What is the MOA of trazodone and Nefazodone?

Answer 16

T - blocks alpha 1 and H1 receptors Low doses - hypnotic, high doses - antidepressant
N - Hepatotoxicity

Question 17

What are the adverse effects of trazodone and nefazodone?

Answer 17

T - sedation, cognitve slowing, dizziness
N - dizziness, somnolence, hepatotoxicity

Question 18

What is the MOA of bupropion?

Answer 18

It blocks dopamine receptor transporter, which inhibits the reuptake of dopamine. This will result in more dopamine binding post-synaptically in the neurons

Question 19

What are the adverse effects of bupropion?

Answer 19

Nausea, Tremor, Insomnia, Dry mouth.

Question 20

What is the MOA of miratazapine and Mianserin?

Answer 20

Block a2 receptors - increase central 5HT and NA
Block 5HT2 and 5HT3 receptors
Block H1 receptors