fragcula

That's likely. I'm using the word in the sense of clinical efficacy, i.e. how likely an intervention is to produce the intended outcome. In this case the response rate to the intervention in those with depression [0].

Preemptive double mastectomy is the most effective way to date to prevent breast cancer [2] (~95% reduction). This is important for those at heightened risk, for example those with pathological variants of BRCA 1 & 2 which each independently increase the risk of breast cancer 5 fold (up to 70%!)[1]. Coupled with other factors some women are statistically almost certain to get breast cancer if they live long enough.

We can't mince words with peoples lives. People with severe depression deserve to know that ECT is a safe treatment and the most effective treatment available. And there should not be stigma in any treatment.

Similarly, pre-emptive mastectomy the most effective prophylactic intervention available for preventing breast cancer. And important for those who are at very very high risk.

No ECT is most certainly the most efficacious treatment for depression we have.

Talking therapies have a respone rate in depression of circa 40% [0], probably just slightly higher for antidepressants up to about 50% and faster [1], ECT respone rate is well over than even for those with treatment resistance but as high as 90% [2]. Vitally, the reposnse to ECT is fast and is often under 10 days.

The fact that ECT is burdensome, limited in availability and stigmatizing (which is why it's got so much legislative structure around it) is not relevant for it's efficacy.

This is spelled out relatively well in the UK's Royal College of Psychiatry statement on ECT [3]

> ECT IS A FIRST-LINE TREATMENT FOR PATIENTS ... where a rapid definitive response for the emergency treatment of depression is needed

This is because it works quickly and reliably to treat depression.

From the medical side what's important is what risk/benefit which is independent.

Antidepressant as a term is really only for convenience which the medications themselves being quite broad in action.

Antipsychotics too are having a bit of a revolution, the first generation seemed to all be about D2 blockade, the second generation acting on 5HT-2a much more than D2. Finally, pimavaserin acting only on seratonin (5HT-2a) and not on dopamine at all [0] now there's SEP-363856 [1] which has action not at D2 or 5HT-2A but TAAR1 and 5HT-1A.

The point is that psychiatrists are not particularly married to any mode of action or mechanism. Only the results.

What people really care about is side effects. That's one of the reasons modern pharmas are so fixated in testing old drugs for new disorders (the other reason is they might be able to get a new patent case in point when Eli Lilly made pink fluoxetine for girls with a new indication for PMS [0]).

Similarly, the best way to identify side effects is by looking at the molecule and guessing (static analysis), testing with cells, animals or other non-human biological systems (I guess this is alpha testing as we rarely think of the testers as human...), and then in human studies (early access).

Even then we roll out incrementally (phase 2), before widely testing in phase 3 and collecting feedback.

This is the key line in the summary.

The concept of attacking an idea no one really believes is really a straw man.

More importantly the modern practice of medicine is "evidence based medicine", not "mechanism based medicine". That means treatments are tested as to if they work, not how they work. Ideally in multiple well run double blinded randomised controlled trials with at least some against treatment as usual. Unlike the past when we thought more about how they might work, theorising something is off about someone's humors and adjusting with leeches.

Anyone looking for a truly mind bending result should look at Hjorth et al. 2021 [0], the study recruited people with social phobia and gave them all an SSRI (escitalopram). Half were told they were getting a sham active placebo and "should not expect to get better", half were told "you're getting the known effective treatment".

Headline result being told you are being treated leads to 4x as much response with brain changes in the dopamin networks.

In the meanwhile, rather than worry about how antidepressants work, why not take a look at electroconvulsive therapy which has proven time and again to be the most effective treatment for depression. Yet we have no idea how it works, other than knowing a decent seizure in those without epilepsy makes you less sad? What on earth.