Type of Drug Strategy
SSRIs Monoamine potentiating drug Inhibits SERT, so blocks 5-HT reuptake on
pre-synaptic terminal
Widest used modern anti- Relatively selective inhibition of Gi coupled 5-HT1A receptor activation co
depressant treatment 5-HT reuptake (than TCAs) this rise initially
But desensitisation of these receptors wit
use leads to greater overall 5-HT signallin
TCAs Monoamine potentiating drug Mostly tertiary amines, that inhibit NET and
pre-synaptic terminals, thus blocking NA an
These and MAOIs were earliest Elevate 5-HT and NA levels, via reuptake.
specific anti-depressant uptake inhibition NET inhibition: relieves biological symptom
treatments SERT inhibition: relieves emotional symptom
"Classic Antidepressant"
SNRIs Monoamine-potentiating drugs Relatively non-selective blockade of NET &
only blocks NET at higher doses.
Non-SSRI based modern Through dual inhibition of 5-HT
antidepressant and NA reuptake
NASSAs Atypical monoamine- Combined antagonist of alpha2 adrenocept
potentiating drugs certain 5-HT receptors (5-HT 2A,C or 3)
CNS Presynaptic alpha2 blockade: increased
release
The increased NA causes greater alpha1 stim
and causes decrease in presynaptic inhibitio
alpha-2
So this alpha2 blockade ends up enhancing
release too
MAOIs Monoamine potentiating drug Inhibit monoamine oxidase A (5-HT substra
(DA substrate)
This and TCAs were the original Through breakdown inhibition Several MAOIs can irreversibly inhibit both
specific antidepressant But MAO-A inhibition thought to be respon
treatments antidepressive effect
"Classic Antidepressant"
, So this alpha2 blockade ends up enhancing
release too
MAOIs Monoamine potentiating drug Inhibit monoamine oxidase A (5-HT substra
(DA substrate)
This and TCAs were the original Through breakdown inhibition Several MAOIs can irreversibly inhibit both
specific antidepressant But MAO-A inhibition thought to be respon
treatments antidepressive effect
"Classic Antidepressant"
Agomelatine Circadian rhythm corrector Action at MT1 receptor and antagonist of 5
Leading to correction of disturbances in circ
rhythms, that commonly occur in depressio
Ketamine Promote glutamatergic surge, Non-competitive, open-channel antagonist
to increase synaptogenesis and NMDARs (Skolnick et al, 1996)
increase cortical
neurotransmission This may lead to NMDAR blockade on GABA
inhibitory interneurons, which promotes
glutamatergic release (disinhibition hypothe
Newer Antidepressants
Vilazodone: SSRI-lile serotonin reuptake inhibitor.
Also a partial agonist of 5-HT1A receptors
Dual proserotonergic mechanism
Causes seemingly faster antidepressant action in animals
Not been replicated in human trials yet though
New agent, so no meta-analyses exist
But appears to have lower risk of:
Weight gain, sexual dysfunction than SSRIs/SNRIs
So there are a variety of monoamine modulating drugs available and in the pipeline
But a 'one size fits all' approach to treatment is inaccurate, and potentially harmful
Fatigue, poor concentration, executive function problems: may benefit more from SNRIs, NASSAs, TCAs
Limbic dysfunction (agitation, worry, insomnia, suicidality): may benefit more from more serotonergically active
Clinical Guideline: First line: monotherapy with established SSRI e.g. Sertraline
Some newer SNRIs may be used instead here though (desvenlafaxine) - if the
If refractive, usually switch to another class of therapy, or add an evidence-ba
SSRIs Monoamine potentiating drug Inhibits SERT, so blocks 5-HT reuptake on
pre-synaptic terminal
Widest used modern anti- Relatively selective inhibition of Gi coupled 5-HT1A receptor activation co
depressant treatment 5-HT reuptake (than TCAs) this rise initially
But desensitisation of these receptors wit
use leads to greater overall 5-HT signallin
TCAs Monoamine potentiating drug Mostly tertiary amines, that inhibit NET and
pre-synaptic terminals, thus blocking NA an
These and MAOIs were earliest Elevate 5-HT and NA levels, via reuptake.
specific anti-depressant uptake inhibition NET inhibition: relieves biological symptom
treatments SERT inhibition: relieves emotional symptom
"Classic Antidepressant"
SNRIs Monoamine-potentiating drugs Relatively non-selective blockade of NET &
only blocks NET at higher doses.
Non-SSRI based modern Through dual inhibition of 5-HT
antidepressant and NA reuptake
NASSAs Atypical monoamine- Combined antagonist of alpha2 adrenocept
potentiating drugs certain 5-HT receptors (5-HT 2A,C or 3)
CNS Presynaptic alpha2 blockade: increased
release
The increased NA causes greater alpha1 stim
and causes decrease in presynaptic inhibitio
alpha-2
So this alpha2 blockade ends up enhancing
release too
MAOIs Monoamine potentiating drug Inhibit monoamine oxidase A (5-HT substra
(DA substrate)
This and TCAs were the original Through breakdown inhibition Several MAOIs can irreversibly inhibit both
specific antidepressant But MAO-A inhibition thought to be respon
treatments antidepressive effect
"Classic Antidepressant"
, So this alpha2 blockade ends up enhancing
release too
MAOIs Monoamine potentiating drug Inhibit monoamine oxidase A (5-HT substra
(DA substrate)
This and TCAs were the original Through breakdown inhibition Several MAOIs can irreversibly inhibit both
specific antidepressant But MAO-A inhibition thought to be respon
treatments antidepressive effect
"Classic Antidepressant"
Agomelatine Circadian rhythm corrector Action at MT1 receptor and antagonist of 5
Leading to correction of disturbances in circ
rhythms, that commonly occur in depressio
Ketamine Promote glutamatergic surge, Non-competitive, open-channel antagonist
to increase synaptogenesis and NMDARs (Skolnick et al, 1996)
increase cortical
neurotransmission This may lead to NMDAR blockade on GABA
inhibitory interneurons, which promotes
glutamatergic release (disinhibition hypothe
Newer Antidepressants
Vilazodone: SSRI-lile serotonin reuptake inhibitor.
Also a partial agonist of 5-HT1A receptors
Dual proserotonergic mechanism
Causes seemingly faster antidepressant action in animals
Not been replicated in human trials yet though
New agent, so no meta-analyses exist
But appears to have lower risk of:
Weight gain, sexual dysfunction than SSRIs/SNRIs
So there are a variety of monoamine modulating drugs available and in the pipeline
But a 'one size fits all' approach to treatment is inaccurate, and potentially harmful
Fatigue, poor concentration, executive function problems: may benefit more from SNRIs, NASSAs, TCAs
Limbic dysfunction (agitation, worry, insomnia, suicidality): may benefit more from more serotonergically active
Clinical Guideline: First line: monotherapy with established SSRI e.g. Sertraline
Some newer SNRIs may be used instead here though (desvenlafaxine) - if the
If refractive, usually switch to another class of therapy, or add an evidence-ba
