I had it in the back of my mind to make a post about this for a long time, but I’ve been concerned with a lot of other stuff. And it can be a bit of an effort to gather and mention all the right sources at the right time, but I won’t try that too much now.
It is about the regulatory protein p11 or also called A100A10. What makes it special is that it causes the expresson of both 5-HT1B and 5-HT4 serotonin receptors, two very important receptors involved in many processes in the brain and body, including hormones and sexuality. [https://pubmed.ncbi.nlm.nih.gov/21300076/]
P11 is mentioned in a lot of studies about stress-induced depression and brain changes [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919643/] and also in studies about antidepressants, though often more as a sidenote.
It is actually known that some side-effects from antidepressants come, not from induction or upregulation of p11, but from its loss. The reason why it is not often talked about is of course because officially antidepressants have no side-effects, or those are just the patients’ fault (and it wouldn’t even matter, because they are just patients).
Nonetheless, it is a known issue, and there is at least a partial treatment which helps a bit. That treatment are freely available Non-Steroidal Antiinflammatory Drugs or NSAIDs like Ibuprofen, Aspirin, Naproxen and others. They vary slightly in their effects, which is why they might not always be noticed in the same way.
The reason why they can help is because of the known regulation of p11 (or S100A10) itself by cytokines. TNF-α and IFN-γ upregulate p11 expression and IFN-α downregulates it.
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107316/]
There are of course myriad other ways, direct and indirect, to influence those factors, but some NSAIDs are a fairly direct way. I personally prefer Ibuprofen.
Here is a study on Ibuprofen, there are actually quite a few on this topic in general:
[https://www.sciencedirect.com/science/article/abs/pii/S030439401830884X]
How would I describe the effect? As a fairly reliable slight improvement of all symptoms, that may vary a bit, based on various factors or conditions. I would primarily recommend it as a support. Dosing should remain moderate to avoid the drugs’ other effects from messing with the wanted effect.
There are probably also other ways to influence p11, like possibly HDAC5 inhibition as mentioned in a study above, and HDAC4 seems to turn up too in context.