Antidepressants

Question 1

Tricyclic Antidepressants (TCA):

Answer 1

amitriptyline (Elavil), desipramine

Question 2

Selective Serotonin Reuptake Inhibitors (SSRI):

Answer 2

fluoxetine, paroxetine, sertraline, (2nd gen)

Question 3

Serotonin & Norepinephrine Reuptake Inhibitors (SNRI):

Answer 3

venlafaxine (2nd gen)

Question 4

Monoamine Oxidase Inhibitors (MAOI):

Answer 4

phenelzine

Question 5

Atypical antidepressants (tetracyclic and
unicyclic antidepressants):

Answer 5

mirtazapine (tetracyclic), bupropion (unicyclic)

Question 6

What are the 4 domains/Sx’s of depression?

Answer 6

Emotional:
- Reduced pleasure, reduced interest in usual activities
- Pessimistic outlook
- Anxiety

Physical:
- Fatigue, sleep disorders (insomnia), appetite disturbances

Cognitive:
- Poor concentration, slow thinking, poor short-term memory, confusion

Psychomotor:
- Agitation
- Slowed speech

Question 7

What is the Serotonin hypothesis?

Answer 7

Depression is related to reduced synaptic levels of serotonin
- 1950’s – Reserpine caused depression in 15% of patients (can downreg. serotonin)
- Most antidepressant drugs appear to work by enhancing synaptic monoamines

Question 8

What are the functions of serotoninergic system?

Answer 8

• Mood
• Memory processing
• Cognition
• Sleep

Question 9

What are the 5 steps of Serotonin neurotransmission?

Answer 9

1. Synthesis
2. Storage
3. Release
4. Bind to receptors
5. Degradation / termination *
   - Uptake by presynaptic serotonin transporter(SERT)
   - Monoamine oxidase (MAO)

Question 10

What is the main target of current Antidepressants?

Answer 10

Degradation / termination
- Uptake by presynaptic serotonin transporter(SERT)
- Monoamine oxidase (MAO)

Question 11

Antidepressants have a _______ onset

Answer 11

SLOW

it takes at least 2 weeks to generate therapeutic effects

Question 12

What is the action site of TCA’s?

Answer 12

Inhibit serotonin and norepinephrine uptake similarly (therapeutic);

Anti-muscarinic, anti-histaminic and anti-adrenergic (α) actions (adverse effects).

Question 13

What are the therapeutic uses of TCA’s?

Answer 13

depression; chronic pain

Question 14

What are the adverse effects of TCA’s?

Answer 14

Sexual dysfunction

Antagonize muscarinic r’s (CNS: confusion, ANS: constipation, dry mouth)

Antagonize a-adrenergic r’s (orthostatic hypo, reflex tachy)

Antagonize histamine (sedation, weight gain)

Overdoses are potential problems (–> coma, resp. depression, seizures & cardiac arrhythmias)

Interact with SSRIs (CYP2D6 inhibitor)

Interact with sedatives, sympathomimetics, antimuscarinics

NOT recom., for elderly pt’s

Question 15

What are the action sites of SSRI’s?

Answer 15

inhibit serotonin reuptake.

Question 16

What are the therapeutic uses of SSRI’s?

Answer 16

First-line treatment (Are safer than TCAs and MAOIs; not more effective than TCAs and MAOIs);

Depression; Anxiety (GAD, PTST, OCD..);

Fluoxetine for bulimia.

Question 17

What are the adverse effects of SSRI’s?

Answer 17

Safer in general;

Sexual dysfunction, weight gain;

Interact with β blockers and TCAs, interact with MAOIs (serotonin syndrome)

Question 18

What are the action sites of SNRI’s?

Answer 18

Inhibit both serotonin and NE reuptake;

Question 19

What are the therapeutic uses of SNRI’s?

Answer 19

depression; anxiety;

Question 20

What are the adverse effects of SNRI’s?

Answer 20

Sexual dysfunction;

Sympathetic symptoms;

Interact with MAOIs (serotonin syndrome)

Question 21

What are the action sites of MAOI’s?

Answer 21

Inhibit monoamine oxidase (metabolism enzyme) → increase monoamines.

Question 22

What are the therapeutic uses of MAOI’s?

Answer 22

depression; usually reserved for patients who don’t respond to other agents.

Question 23

What are the adverse effects of MAOI’s?

Answer 23

sexual dysfunction; weight gain; overdose

Interact with SSRIs, SNRIs, TCAs (serotonin syndrome); interact with foods containing tyramine.

Question 24

What are the action sites of Atypical’s?

Answer 24

Mirtazapine (Remeron)
Action sites:
- Structurally a tetracyclic compound
- Increasing norepinephrine and serotonin release
- Potent blocker of histamine H1 receptors

Bupropion:
Action sites:
- Structurally an unicyclic compound
- Largely unknown; No direct effects on the serotonin system.

Question 25

What are the therapeutic uses of Atypical’s?

Answer 25

Mirtazapine (Remeron)
- Depression that is unresponsive to SSRI and SNRI
- Might be added to an SSRI or SNRI to augment
antidepressant benefit

Bupropion:
- Might be added to an SSRI or SNRI to augment antidepressant→ benefit if monotherapy is unsuccessful.
- Smoking cessation.
- Have some benefits in treating obesity.

Question 26

What are the adverse effects of the Atypicals?

Answer 26

Mirtazapine (Remeron)
- Sedation
– Drug interactions: may be additive with those of CNS
depressants such as alcohol and benzodiazepines
- Weight gain
- not commonly associated with sexual effects.

Bupropion:
- Can include headache, dizziness, insomnia, seizures: much lower incidence than TCA’s
- No sexual dysfunction, no weight gain, and no sedation adverse effects
- Drug interactions: inhibit CYP 2D6
– Interact with many drugs such as β blockers and TCAs
→ increase plasma β blockers and TCAs levels.

Question 27

How long do Antidepressants take to generate therapeutic effects?

Answer 27

take at least 2 weeks

Question 28

SSRIs are…

Answer 28

first-line agents for MDD and anxiety disorders.

Question 29

SNRI’s are…

Answer 29

also first-line agents for MDD.

Question 30

TCAs and MAOIs:

Answer 30

• second- or third-line treatments for MDD.
• is reserved for patients who have been unresponsive to other agents.

Question 31

Mirtazapine and bupropion:

Answer 31

• Mirtazapine: SSRI or SNRI non-responders
• Added on drugs for an SSRI or SNRI
• No sexual dysfunction adverse effects.