The MonoAmine Hypothesis

Question 1

What are some common SE’s associated with Antidepressants?

Answer 1

Weight gain

Sexual Dysfunction

Question 2

What NT is associated with sexual dysfunction?

Answer 2

5HT

Question 3

Where is the 5HT1aR found?

Answer 3

frontal cortex and the brain stem raphe

Question 4

What does buspirone target?

Answer 4

The 5HT1aR

Question 5

How does buspirone work?

Answer 5

it is an agonist of the receptor. It increases DA and NA release in the VA. This causes a decrease in glutamate activity and subsequent decrease in the GBAA interneurone activity

Question 6

Who studied polymorphisms in the 5HT1aR?

Answer 6

Letsch and Guthnect 2004

Question 7

What did neumeister et al prove?

Answer 7

There was decreased 5HT1aR’s in panic disorder patients

Question 8

What is vortioxetine?

Answer 8

an SSRI and strong agonist of the 5HT1aR
Partial agonist at the 5HT1bR (mork et al 2012)
5HT3,7 and 1d antagonist

Question 9

What did a review by Kohler et al 2016 mention about the use of vortioxetine?

Answer 9

7 placebo controlled 6-8 week studies including one in the elderly subjects which have demonstrated the efficacy of vortioxetine in MDD. Ranges from 5- 20mg per day.

Question 10

What is vilazadone?

Answer 10

SSRI

5HT1a agonist

Question 11

Which novel anti-depressant is licensed by the FDA?

Answer 11

Vilazadone (Singh et al. 2012)

Question 12

How does vilazadone work?

Answer 12

SSRI and 5HT1ar agonist + the antagonism of 5HT1a autoreceptors in addition to post synaptic stimulation

Question 13

What clinical trials are there for vilazadone?

Answer 13

2 randomised double blind trials in adults with MDD; vilazadone 40mg was shown to be significantly higher Than placebo in improving MDD symptoms (Khan et al 2014)

Question 14

How do benzodiazepines treat anxiety?

Answer 14

increasing the potency of the GABAa receptor function

Question 15

Where is there increased excitatory neurotransmitter which is implicated in anxiety?

Answer 15

Forebrain (gross and hen 2004)

Question 16

What did gross and hen 2004 show?

Answer 16

Direct injection of buspirone into the forebrain regions e.g. hippocampus and amygdala produced an anxiolytic profile through buspirone induced activation of the 5HT1a auto receptors

Question 17

How do benzodiazepines work?

Answer 17

Act at the GABAa receptors

Question 18

How does buspirone work?

Answer 18

acts at the 5HT1aR

Question 19

How do SSRIs work?

Answer 19

block the reuptake of 5HT (increasing the duration of 5HT in the synaptic cleft) - slow therapeutic onset

Question 20

How do beta blockers work?

Answer 20

act by blocking peripheral/ central NA activity

Question 21

When do we use atypical antipsychotics?

Answer 21

as an adjunct therapy for treatment resistant PCD/ PTSD

Question 22

What are the limitations of current anti-depressants?

Answer 22

Efficacy in less than 40%
robust effect in preventing relapse in MDD
tolerability - weight gain and sexual dysfunction
time of onset - 4-6 weeks
safety - risk of suicide

Question 23

What type of receptor are 5HT1aR?

Answer 23

GPCR’s - Gai/ Gaby closes the Ca2+ presynaptically; and opens the K+ channels causing hyper polarisation