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Why do antidepressants take so long to reach efficacy? I've read of theories about it perhaps being due to the strength of negative feedback via serotonergic and adrenergic autoreceptors during the first few weeks of treatment. What I'm looking for in an answer is the following:

  • The current theories regarding why currently-in-practise antidepressant regimens have a delayed onset of action.
  • The evidence for this theories.
  • How these theories fit in with the monoamine hypothesis or whether it is inconsistent with the monoamine hypothesis and how.
  • Possible solutions to this problem of delayed responses to antidepressant therapy.

All of this is strictly theoretical, there are no actual people involved here, this is simply a scientific inquiry.

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1 Answer 1

With respect to the class of specific serotonin reuptake inhibitors (SSRIs) the delayed action (say, 2 weeks) can be explained by their action on 5HT1A receptors in the dendritic region. This changes the firing pattern of the serotonergic neuron into a more fluttering mode over time, so that it releases more serotonin (5HT) Lucas et al. (2007). More 5HT makes you feel better. That is how it fits into the monoaminergic hypothesis. To have the 5HT1A receptors respond this way takes time, as it is an adaptive response that has to do with downregulation of 5HT1A receptors.

This is only an expanation of delayed action of SSRIs, a specific subclass of antidepressants. For example, there are newer classes of antidepressants that seem to work faster (5HT4 action) Lucas et al. (2007).

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All regulatory administration (any reg. admin, FDA, TGA, EMA, MHRA, etc.)-approved antidepressants have a delayed onset of action, although mirtazapine may act slightly faster. So it isn't just the SSRIs. Even antidepressants with no appreciable serotonergic effects (e.g., bupropion) have a delayed onset of action. –  Brenton Horne 22 hours ago
    
Intetesting! I wasn't aware of that. I have made some changes in my answer, as it applies to SSRIs only. Thanks! –  Chris Stronks 22 hours ago

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