Because psychiatric drugs don't necessarily work by counteracting specific deficits in the brain. That's a myth driven by unfortunate marketing campaigns and surface-level misunderstandings of the science.

This makes intuitive sense to people when discussing other topics. For example, when someone is in pain they don't need to have an "endogenous opioid deficiency" for opioid painkillers to alleviate their pain. They're just in pain, and modulating the opioid system with drugs is one way we can reduce that pain. Or COX-2 inhibitors. Or a number of other substances.

Likewise, modulating the serotonin system with SSRIs is one way we can modulate depression symptoms. People don't need to have a "serotonin deficiency" to see benefits from modulating their serotonin system.

Depression has no common cause or common set of symptoms. I read a paper that likened it to a watershed, with tributaries feeding into a general pool of malaise. The watershed varies from person to person, and affects their internal “ecosystem” differently.

Maybe it’s a bit cute, but with this understanding, I think the headline is not shocking. We will never find the one cause of depression because there isn’t one.

In my opinion, our best bet is more personalized medicine: helping people identify which rivers are filling up their lake of depression. For most people it will be a weighted combination of many things, but I think there will usually be some principal components.

It might be a different mechanism, like brain-derived neurotrophic factor[1].

[1]: https://www.science.org/content/blog-post/how-antidepressant...

Correlation isn't causation. The serotonin effect may be a symptom of the depression. Treating symptoms is sufficient intervention for many.

If we don't understand the mechanism of action it can still cause an effect. After all SSRIs certainly cause plenty of other side effects.

> ...two recent meta-analyses question this picture. The first meta-analysis used data that were submitted to FDA for the approval of 12 antidepressant drugs. While only half of these trials had formally significant effectiveness, published reports almost ubiquitously claimed significant results. "Negative" trials were either left unpublished or were distorted to present "positive" results. The average benefit of these drugs based on the FDA data was of small magnitude, while the published literature suggested larger benefits.

> ...A second meta-analysis using also FDA-submitted data examined the relationship between treatment effect and baseline severity of depression. Drug-placebo differences increased with increasing baseline severity and the difference became large enough to be clinically important only in the very small minority of patient populations with severe major depression. In severe major depression, antidepressants did not become more effective, simply placebo lost effectiveness.

> These data suggest that antidepressants may be less effective than their wide marketing suggests. Short-term benefits are small and long-term balance of benefits and harms is understudied.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2412901/

My guess, without digging into the study itself since I'm on mobile, is that there is no singular cause for depression. Rather, depression is simply a symptom of a wide range of causes, with one possible cause being low serotonin (or a reduced sensitivity to it). Or even, low serotonin is a symptom of the depression.

Not all patients with depression find relief from SSRIs, or medications in general, but some certainly do.

It's mostly a placebo

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299662/