The MonoAmine Hypothesis Flashcards
What are some common SE’s associated with Antidepressants?
Weight gain
Sexual Dysfunction
What NT is associated with sexual dysfunction?
5HT
Where is the 5HT1aR found?
frontal cortex and the brain stem raphe
What does buspirone target?
The 5HT1aR
How does buspirone work?
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
Who studied polymorphisms in the 5HT1aR?
Letsch and Guthnect 2004
What did neumeister et al prove?
There was decreased 5HT1aR’s in panic disorder patients
What is vortioxetine?
an SSRI and strong agonist of the 5HT1aR
Partial agonist at the 5HT1bR (mork et al 2012)
5HT3,7 and 1d antagonist
What did a review by Kohler et al 2016 mention about the use of vortioxetine?
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.
What is vilazadone?
SSRI
5HT1a agonist
Which novel anti-depressant is licensed by the FDA?
Vilazadone (Singh et al. 2012)
How does vilazadone work?
SSRI and 5HT1ar agonist + the antagonism of 5HT1a autoreceptors in addition to post synaptic stimulation
What clinical trials are there for vilazadone?
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)
How do benzodiazepines treat anxiety?
increasing the potency of the GABAa receptor function
Where is there increased excitatory neurotransmitter which is implicated in anxiety?
Forebrain (gross and hen 2004)
What did gross and hen 2004 show?
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
How do benzodiazepines work?
Act at the GABAa receptors
How does buspirone work?
acts at the 5HT1aR
How do SSRIs work?
block the reuptake of 5HT (increasing the duration of 5HT in the synaptic cleft) - slow therapeutic onset
How do beta blockers work?
act by blocking peripheral/ central NA activity
When do we use atypical antipsychotics?
as an adjunct therapy for treatment resistant PCD/ PTSD
What are the limitations of current anti-depressants?
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
What type of receptor are 5HT1aR?
GPCR’s - Gai/ Gaby closes the Ca2+ presynaptically; and opens the K+ channels causing hyper polarisation
