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The monoamine hypothesis postulates that the deficit of certain neurotransmitters is responsible for depression, and even that certain neurotransmitters are linked to specific symptoms.

If suppose serotonin deficit causes depression and antidepressants like TCAs causes increase in serotonin by decreasing uptake, it concludes to me that the increase in transmission via serotonergic receptors on post synaptic membrane alleviates depression.

My question is that how do antidepressants like atypical antidepressants more specifically Trazodone which acts as 5-HT2 antagonist show their antidepressant action? And TCAs also show such antagonism.

I believe the idea of increased serotonin to cause antidepressant action is not being satisfied here especially in this case of atypical antidepressant as the transmission is being blocked by serotonin receptor antagonistll.

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    $\begingroup$ Did you search for articles online? There must be hypotheses and reviews on how different types of antidepressants are thought to be working. $\endgroup$ – CopperKettle Jan 20 '19 at 18:27
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    $\begingroup$ @CopperKettle I did but they didn't seem to clearly explain like as to why in one case serotonin increase causes antidepressant action and on the other hand antagonism to serotonin receptors causes antidepressant action. $\endgroup$ – Sikander Jan 20 '19 at 19:08
  • $\begingroup$ The wikipedia page you linked to lists 10 atypical antidepressants. Sampling a few of them I see they have different mechanisms of action. So doesn't it seem unlikely there's a single explanation for all of them? $\endgroup$ – Carey Gregory Jan 20 '19 at 23:30
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    $\begingroup$ This is a topic discussed in primarily in psychiatry literature. There are a lot of theories on this. I am not up-to-date enough on that literature to be certain, but I do not think there is yet a clear answer to this. There appear to be more than one mechanism of depression, as well as it being clearly more complex mechanism than simple serotonin deficiency. $\endgroup$ – DoctorWhom Jan 21 '19 at 10:37
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    $\begingroup$ @CareyGregory I tried to make the question more specific regarding the mechanisms, focusing more on serotonin uptake and transmission since it is of concern to me now. $\endgroup$ – Sikander Jan 21 '19 at 12:32

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