Depression treatment failure, what if biomarkers existed that often predicted why treatment outcomes succeed or fail and a polypharmacy of drugs that might provide a panacea for many insults and illnesses. It has long been hypothesis BUT never tested by straightforward and available science methods for drug R&D. Not of much academic or corporate interest, NO big money or great glory in generic drugs, science selected supplements, underpinned with good diet and lifestyle. Further whether depression or long COVID immune activation-dysfunction neuroimmunology may take time, even years to ameliorate.

Good article to start, there is much more if you search [depression inflammation].

The Role of Inflammation in Depression and Fatigue. https://www.ncbi.nlm.nih.go...

Many drugs, peptides and compound to include many neurotropic drugs have secondary pleotropic anti-inflammatory action. The nervous and immune systems are evolutionarily integrated some cytokines and other immunomodulator and neurotransmitter e.g. IL-1, PAF, have dual functions in both systems. This is reflected in the field of neuroimmunology for many decades and Immunopsychiatry for over a century. I have published on the use of anti-inflammatory on-label and "repurposed" pleotropic drugs and compounds, especially in synergy, multi-threat medical countermeasures [search term] to treat many insults and pathology.

We can do the research on dual systems and pleotropic countermeasures or continue to pretend it's all in your head.

That the researchers "were surprised by the high humanistic and economic burden for patients with mild MDD who self-reported a prior treatment failure" is horrifying but to be expected. (byw, "humanistic" is misused in that sentence; being clinically depressed has little to do with humanism; correct language matters.) Much of this article reports how research into not-entirely-physical illness is biased. It's biased toward things that can be measured and learned about by the use of statistics. But depression is "subjective"; instances of it have to be protected from seeming merely "anecdotal" by being forced into unhelpful categories. Who determines "severe"? what does "mild" mean? Why is a depressed patient's concurrent anxiety considered a comorbidity instead of part of the same illness? The same goes for PD, PTSD, OCD, ADD, et al. Sure, it costs almost $600 for an emergency-room visit where I live, but what does that fact add to our knowledge of what depressed people are experiencing or what can and should be done to alleviate their suffering? Moreover, if a patient works for a good employer, missing work costs her nothing in money, but otherwise the high-salary patient's loss of income must count "objectively" as more than the patient whose job pays $14/hour, whose loss of income is relatively greater in the context of her smaller budget).

It's nice to know depression is the focus of research. It would be nicer if the research actually helped depressed patients. It would be nicer still if there were a cataclysmic revolution in our culture's whole approach to mental and emotional health.

Anon-Scientist we do collective thumps-up on this and many other posts. If we every encounter in the real world, I post under my name, introduce yourself, happy to buy bottoms-up on beverage of your choosing.