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If someone is going through SSRIs to find one that works, doesn't it make sense to target each receptor in turn rather than the same one with different drugs (like prozac and zoloft, for example)? Is this considered when prescribing anti-depressants?

Is it even possible?

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    $\begingroup$ What do you mean by "each receptor in turn"? Which receptors? $\endgroup$
    – Bryan Krause
    Jan 5 at 19:59

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Short answer, no.

After lifestyle changes (optimising diet, exercise and social engagement) and psychotherapy (e.g. cognitive-behavioural therapy) have been trialled, most psychiatrists will commence a patient on selective serotonin reuptake inhibitor (SSRI), like Prozac or Zoloft. If this is trialled at a reasonably high dose for several weeks with no benefit, they'll usually switch to either another SSRI or a selective serotonin and noradrenaline reuptake inhibitor.

Most psychiatrists are not thinking about the specific receptors beyond serotonin and noradrenaline transporters because we don't have data to suggest this makes a clinical difference. For example, Prozac is an agonist at the sigma-1 receptor and the Zoloft is an antagonist at that receptor... but what that means for an individual patient, we don't know.

Some psychiatrists now consider an individual's genetic make-up when choosing a medication. This is an area called pharmacogenetics. See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299682/ for a paper we wrote on the topic if you're interested.

Hope this helps.

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  • $\begingroup$ I listen to a lot of podcasts (like andrew huberman) where they talk about studies and bring up all the different receptors and effects. Moreover, the wikipedia articles of SSRIs say what receptors they have an effect on. What studies show it doesnt make a difference and how does that square with all the scientists i've heard talking about their research on them? $\endgroup$ Feb 15 at 22:51
  • $\begingroup$ Your question should be the other way around - what studies show that receptor affinity makes a significant difference to clinical outcomes beyond class effects? Pubmed is freely available and you can have a look at the abstracts for free. $\endgroup$ Feb 15 at 23:09
  • $\begingroup$ I hardly have the knowledge for that. I just know that when reading/hearing people talk about medications or drugs subtypes and subtype differences are mentioned a lot. Yet that heavily contrasts with the approach psychiatry takes which is so simple it seems i could do it. just throw a dart a medication and hope it does something. $\endgroup$ Feb 15 at 23:29
  • $\begingroup$ Yes, it's not the best approach. There is research underway to try to develop a more personalised approach to psychiatric treatment rather than using a 'one size fits all' approach. But this is still some way off. $\endgroup$ Feb 15 at 23:32

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