Antidepressants (General)

Question 1

Unipolar Depression

Answer 1

One direction of depressive symptoms

Question 2

Bipolar Disorder

Answer 2

Depression alternating with mania

Question 3

Depression Symptoms

Answer 3

Emotional:
- Sadness, Anxiety, Overwhelmed

Biological:
- Aches, Headaches, Sleep disturbance, Significant weight changes

Question 4

Depression Pathophysiology (Monoamine Theory)

Answer 4

Depression is caused by deficient of monoamine transmitters, noradrenaline, and 5-HT

Mania is caused by excess

Question 5

Evidence of Monoamine Theory

Answer 5

Tricyclic Antidepressants blocks NE and 5-HT reuptake
–> Increase NE and 5-HT in synapse
–> Increase mood

Reserpine inhibits NA and 5-HT storage
–> Decrease NA and 5-HT in body
–> Decrease body

Question 6

Issues with Monoamine Theory

Answer 6

Inconsistent Result:
- Neurochemical effects of antidepressants is very rapid, however, antidepressant effects take weeks to form
–> What is happening in between giving monoamine and its antidepressive effects

• Ketamine’s antidepressant effect works rapidly, however, it does not increase NA

Question 7

Depression Neuroendocrine Mechanism
(Cortisol)

Answer 7

HPA Axis (Hypothalamus-Pituitary-Adrenocortical)

Stimulation of HPA (Caused by stress, illness, time of day, etc.)
- Hypothalamus releases CRH
- Anterior Pituitary releases ACTH
- Adrenal Glands release Cortisol (Stress Hormone)

Question 8

Depression Neuroendocrine Mechanism
(Glutamate)

Answer 8

Stress enhances the excitotoxic effects of glutamate mediated by NMDA receptors
–> Expression of genes that promotes neural apoptosis

Question 9

Depression Neuroendocrine Mechanism
(Neuron Loss)

Answer 9

Cortisol and Excitotoxic Glutamate promote Detrimental Gene Transcription Responses
–> Promotes Neural Apoptosis
–> Inhibits Neurogenesis

Promoting Depressive Symptoms

Question 10

Depression Neuroendocrine Mechanism
(Neuron Gain)

Answer 10

NA, 5-HT, BDNF (Brain Derived Neurotrophic Factor) promote Beneficial Gene Transcription Responses
–> Promotes Neurogenesis
–> Inhibits Neural Apoptosis

Promoting Depressive Symptoms

Question 11

Conventional Anti Depressants
(Inhibitors of Monoamine Uptake)

Answer 11

• Selective Serotonin Reuptake Inhibitors (SSRIs)
• Tricyclic Antidepressants (TCAs)
  –> NE and 5-HT Reuptake Inhibitors
• Mixed 5-HT and NE Reuptake Inhibitors
  (SNRIs)
• NE Dopamine Reuptake Inhibitors (NDRI)
• St John’s Wort
  –> 5-HT and NE Reuptake Inhibitor

Question 12

Conventional Anti Depressants
(Receptor Blocking Antidepressant)

Answer 12

Serotonin-2 Antagonists / Serotonin Reuptake Inhibitors (SARI)
–> Blocks 5HT-2

Noradrenergic/Specific Serotonergic Agent (NaSSA)

Question 13

Monoamine Oxidase Inhibitors (MAOI)

Answer 13

• Irreversible, non competitive, non selective inhibitors
  –> Inhibit MAO-A and MAO-B
  (Phenelzine, Tranylcypromine)
• Reversible, MAO-A Selective Inhibitors
  (Moclobemide)

Question 14

Rapid Acting Antidepressants (RAADs)

Answer 14

Non-Competitive NMDA Receptor Channel Blocker
- Ketamine

Question 15

Effects of Antidepressants
(NE Reuptake Blockade)

Answer 15

Antidepressant Effect, Vasoconstrictor
Side Effect: Too much NE
- Causes tremors, tachycardia, and erectile problems
–> Avoid using with anything that increases heart rate

Question 16

Effects of Antidepressants
(5-HT Reuptake Blockade)

Answer 16

Antidepressant, Anti-Anxiety, Anti-Panic, Anti-Obsessional

Side Effects: Affects other 5-HT Receptors
- Nausea, Dyspepsia, Headache, Sexual Side Effects

Potentiation of drugs with serotonin properties, caution regarding serotonin syndrome

Question 17

Effects of Antidepressants
(DA Reuptake Blockade)

Answer 17

Elevate Prolactin

Side Effects: Too much DA
- Aggravation of Psychosis

Question 18

Effects of Antidepressants
(5-HT1A Agonism)

Answer 18

Antidepressant, Anxiolytic, Anti Aggressive

Question 19

Effects of Antidepressants
(5-HT2A Blockade)

Answer 19

Anxiolytic, Antidepressant, Antipsychotic, Antimigraine, Improved Sleep

Side Effects:
- Hypotension, Ejaculatory Problems, Sedation, Weight Gain

Question 20

Effects of Antidepressants
(M1 Ach Blockade)

Answer 20

Dry mouth, blurred vision, urinary retention, constipation
Makes anticholinergic drugs stronger

Question 21

Effects of Antidepressants
(H1 Blockade)

Answer 21

Side Effects: Sedation, Postural Hypotension

Question 22

Effects of Antidepressants
(a1 Blockade)

Answer 22

Side Effects: Postural Hypotension, Dizziness, Reflex Tachycardia

Question 23

Effects of Antidepressants
(a2 Blockade)

Answer 23

CNS Effect: Possible decrease in depressive symptoms

Question 24

Adverse Effects of SSRIs

Answer 24

Enhanced effect on 5-HT Receptors
- Nausea, anorexia, insomnia, headache, nervousness, sexual dysfunction

Risk of Serotonin Syndrome

QT Interval Prolongation –> Citalopram

Question 25

Serotonin Modulator and Stimulator Benefits

Answer 25

Vortioxetine is more specific Agonist: 5-HT1A and 5-HT1b Antagonist: For other 5-HT Due to being a specific agonist and its antagonist action --> Lower Side Effects - Less sedation - Less insomnia - Less weight gain

Question 26

Serotonin-1A Agonist / Serotonin Reuptake Inhibitor (Mechanism)

Answer 26

Vilazodone SSRI Agonist for 5-HT1A

Question 27

Secondary Amines (Effects)

Answer 27

Greater NE Reuptake Inhibition than 5-HT effect --> More NE Side Effects

Question 28

Tertiary Amines (Effects)

Answer 28

More 5-HT Reuptake Inhibition --> More 5-HT Side Effects

Question 29

TCAs (Side Effects)

Answer 29

Affect Muscarinic, Histamine, and 5-HT Receptors Overdose: Arrhythmia - Anticholinergic --> Dry mouth, blurred vision, constipation, urinary retention - Antihistamine --> Sedation - Antimuscarinic

Question 30

Venlafaxine

Answer 30

Non-Selective for 5-HT and NE uptake - 5-HT Reuptake Inhibitor at low dose - NE Reuptake Inhibitor at high dose Similar to TCAs, lack major receptor blocking actions --> Fewer Side Effects

Question 31

Bupropion

Answer 31

NDRI: NA and DA reuptake inhibitor Helps in quitting smoking Lowers seizure threshold - Makes it easier to get seizure --> Do not use with patients that are in risk of seizure

Question 32

Trazodone

Answer 32

SARI: Serotonin 2 Antagonist + Serotonin Reuptake Inhibitor Blocks 5-HT2A and 5-HT2C Blocks 5-HT Reuptake Strong sedation effect: - Should be taken at night

Question 33

Mirtazapine

Answer 33

NaSSA: Noradrenergic/Specific Serotonergic Agent Blocks alpha 2 adrenoceptor and 5-HT2C receptors --> Enhance NA and 5-HT release Potent Antihistamine effect at H1 Also blocks 5-HT2A and 5-HT3 receptors - Less sexual dysfunction and nausea side effects No anticholinergic side effects

Question 34

Monoamine Oxidase (Different Types)

Answer 34

MAO-A (Main Antidepressant Target) - Degrades 5-HT and NE MAO-B - Degrades phenylethylamine and dopamine

Question 35

Hypertensive Crisis

Answer 35

MAO in gut inactivates amines like tyramine - Tyramine produces unwanted effects If using a MAO inhibitor then there is no MAO to inactivate Tyramine --> Can cause hypertensive crisis Also avoid using OTC cough/cold agents that contain sympathomimetics