Antidepressants

Question 1

What is the theory that explains what causes depression?

Answer 1

Deficits in monoamine neurotransmitters cause depression

Question 2

Are monoamines the only cause of depression?

Answer 2

Most likely monoamines are important but there are complex interactions with other neurotransmitter systems as well

Question 3

What are the functions of MAO-A and MAO-B?

Answer 3

5HT is mainly broken down by MAO-A

NA and dopamine - MAO-B

Question 4

MOA of MAOIs

Answer 4

Increase bioavailability of monoamines by inhibiting the enzyme that degrades the neurotransmitters

Question 5

How does selegiline work?

Answer 5

MAO-B selective inhibitor, works to preserve dopamine

Question 6

What is phenelzine?

Answer 6

Non-selective for MAO-A and MAO-B

Irreversible MAOI

Question 7

Adverse effects of MAOIs

Answer 7

Postural hypotension (due to sympathetic block by accumulation of dopamine in the cervical neck ganglia, where it acts as a inhibitory transmitter)
Restlessness and insomnia 
Should not be combined with other drugs enhancing serotonergic function (e.g. pethidine)

Question 8

What is the cheese reaction?

Answer 8

Drug food interaction leading to acute hypertension
Major danger from cheeses and concentrated yeast products
Amines (eg tyramine) in foods are usually broken down by MAO in the intestines and liver. MAOIs can lead to accumulation of tyramine and sympathomimetic effect (tyramine competes with noradrenaline for the vesicular compartment, leads to more release of NA)

Question 9

With what agents is the cheese reaction less likely to occur?

Answer 9

Less likely to occur with reversible MAO-A selective (eg moclobemide) than irreversible non-selective MAOIs (phenelzine)
MAO-B can still work, and mechanism is reversible

Question 10

Types of antidepressants

Answer 10

MAOIs
TCAs 
SSRIs
NARI 
SNRI 
NaSSA
NDRI 
Melatonin receptor agonist 
Glutamate NMDA antagonist
Multimodal serotonergic antidepressant

Question 11

MOA of TCA

Answer 11

Prevent monoamine from being reuptake into the synapse to let them stay in the synapse for longer → increases levels of monoamines

Question 12

TCAs

Answer 12

Imipramine, amitryptiline, nortryptiline

Question 13

Adverse effects of TCAs

Answer 13

Sedation (H1 antagonism) 
Postural hypotension (alpha adrenergic sympathetic block) 
Dry mouth, constipation, blurred vision (muscarinic receptor antagonism)

Question 14

SSRIs vs TCAs

Answer 14

SSRIs have greater 5HT reuptake transporter selectivity than TCAs
Fewer side effects (but still antimuscarinic, sedation and postural hypotension)

ADVANTAGES:

• Improved adverse effect profile of SSRIs leads to better compliance and prescription of more adequate doses
• Safer in overdose

Question 15

SSRIs

Answer 15

Fluoxetine, citalopram

Question 16

Advantages of SSRIs

Answer 16

Low affinity for alpha-adrenoceptors
Lack of effect at histamine receptors
Low affinity for muscarinic

Question 17

AEs of SSRIs

Answer 17

Nausea and insomnia
Sexual dysfunction
Sedation (citalopram)

Question 18

Serotonin syndrome - caused by what and what are the effects?

Answer 18

Severe reaction from drug-drug interactions with other drugs increasing serotonergic activity
Tremor, hyperthermia, cardiovascular collapse

Question 19

NARI

Answer 19

reboxetine

Question 20

NARI adverse effects

Answer 20

dry mouth, constipation, insomnia, tachycardia

Question 21

Mirtazipine

Answer 21

NaSSA
Norepinephrine and specific serotonin antidepressant
Antagonist of adrenergic alpha2-autoreceptors and 5-HT receptors

Question 22

Bupropion

Answer 22

Noradrenaline dopamine reuptake inhibitor

Question 23

Ketamine

Answer 23

Glutamate NMDA receptor antagonist used as an anesthetic, currently evaluated for rapid-onset antidepressant effect

Question 24

Vortioxetine

Answer 24

Multimodal serotonergic antidepressant
Additional receptor affinities may result in further release of serotonin and other neurotransmitters
May be efficacious in patients resistant to other antidepressants
May also have pro-cognitive effects
May increase risk of suicidal thoughts or actions in children and teens