> You look at a patient who doesn't get out of bed, is in trouble at work/school for performance, doesn't spend social time with friends, etc, and 6 months after starting an SSRI they're indistinguishable from other people but still have other issues, we call that a "mild impact" because they self-report other problems.

This really lines up with what I've seen anecdotally. My partner literally doesn't remember how bad things were before he took antidepressants because depression impacted his ability to form memories. He self reports that antidepressants had a mild impact, but from an outside perspective nearly everything about his life changed.

> But you pivot to TMS and you see 60-80 percent improvement rates. Esketamine is close too.

I have received both rTMS and esketamine and the providers themselves told me they saw roughly a 30-40% response rate (not remission, that's even lower!). Upon researching the topic myself, I found that the meta analysis usually agreed with this 30% figure, but recent research papers mark eskatamine even lower. Both treatments can be miraculous for a few select people and it makes a good headline, but it's a total failure for the majority of people.

I agree with you that those treatments should be easier to access, though.

> Too many therapists dismiss meds and too many psychiatrists dismiss therapy.

This is the only factually true statement in your entire comment.

The problem with the entire argument that you're making is that the natural rate of remission in uncomplicated major depressive episodes is very close to the rate that SSRIs create, individually, and very close in terms of timing. If you do something more like STAR-D you see higher rates, but that also takes so long that many people naturally remit.

Well I think that we do not know enough about genesis of depression and other mental issues. So this is just symptomatic therapy. And as such it should be prescribed only for very short terms. Analogy: how would you perceive someone who prescribed his febrile patient paracetamol for 10 years just because it works? And in his defense he/she claims that febrile condition has well known metabolic chain and that paracetamol lowers fever mainly by interrupting the COX → PGE₂ part of the fever pathway in the brain.

> The truth is antidepressants have a larger effect on mental health than actually gets reported because of how improvements are measured.

The truth is actually exactly the opposite, and I provided very high-quality evidence demonstrating this to be the case. You have nothing but bald assertions.

For some people the emotional blunting is desirable, especially as you said, if the problem is chronic anxiety. But for many other people, their depression is defined by a lack of positive affect and anhedonia, meaning that emotional blunting is literally making things worse.

Depression is highly heterogenous, and I am glad the medication helped you.

SSRIs have much more clinical evidence of efficacy for addressing anxiety disorders vs a placebo than depression. The effect size is ~0.7 vs 0.2 in meta studies.

> I find it funny that people complain about emotional blunting when that is the entire purpose of the drug.

The ideal would be to blunt the negatives but not the positives. The effect of some of the older antidepressants can be to blunt both, across the board.

Some of the newer atypical antidepressants can address depression without making everything flat.

See also: The Serotonin Theory of Depression: a Systematic Umbrella Review of the Evidence (2022). It's worth reading the introduction and results in full, but here are two important quotes (footnote markers removed):

> Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity. Most studies found no evidence of reduced serotonin activity in people with depression compared to people without, and methods to reduce serotonin availability using tryptophan depletion do not consistently lower mood in volunteers. High quality, well-powered genetic studies effectively exclude an association between genotypes related to the serotonin system and depression, including a proposed interaction with stress.

> The chemical imbalance theory of depression is still put forward by professionals, and the serotonin theory, in particular, has formed the basis of a considerable research effort over the last few decades. The general public widely believes that depression has been convincingly demonstrated to be the result of serotonin or other chemical abnormalities, and this belief shapes how people understand their moods, leading to a pessimistic outlook on the outcome of depression and negative expectancies about the possibility of self-regulation of mood. The idea that depression is the result of a chemical imbalance also influences decisions about whether to take or continue anti-depressant medication and may discourage people from dis-continuing treatment, potentially leading to lifelong dependence on these drugs.

https://www.nature.com/articles/s41380-022-01661-0

Yup, I would agree. The meta-research / methodological research and awareness here is really quite impressive, even though its conclusions are a bit grim and not well-known.

Have we reigned in the number of perscriptions?

Because the 1 in 10 stat I find seems a bit low, at least in my circle, and those are the ones who are open about it.

And the people I know have been on them approximately a decade. What baffles me is that a fair number of them triggered their own depressive episodes, and likely did need therapy and something at the time - but have all long since move past those "moments".

> As you point out, placebo antidepressants are fairly effective.

This is a misunderstanding of concepts like regression to the mean, and also the active placebo elements involved.

> but the experienced reality is that they help people a lot

And the evidence is that the reality people think they are experiencing is wrong, i.e, they are improving and factually experiencing improvement, but misattributing the cause to the drug.

> "As effective as placebo" does not mean worthless

In one sense of worthless, perhaps, but since drugs have larger costs relative to placebo, well, we can argue they are worse than worseless in another.

Better instead to talk about cost-benefit tradeoffs, number-needed-to-treat vs number-needed-to-harm and etc though, and try to get better at prescribing more carefully to those they clearly benefit.

It’s unethical to prescribe a patient a placebo in a way that suggests that what they are receiving is scientifically proven.

In a clinical trial setting, you can prescribe a placebo, because the patient is fully aware and clearly consenting to the fact that they may receive a placebo. Lying to a patient, in a clinical setting, from a position of authority, is a completely different matter. The informed consent would be completely absent, the patient’s ability to make informed choices about their own healthcare would be undermined and withheld, and the provider would be deriving financial benefit from the patient and / or through insurance claims for what amounts to a scam.

The patient, who would be seeking a treatment from a trusted expert, would believe that they are receiving proven treatments in exchange for their time, patience, money, reduced quality of life due to side effects, and opportunity costs in terms of not going to a different provider or trying something else, but in reality their provider would be misleading them. Some patients would even die as a result of taking a particular placebo and depending on it—either because of side effects or due to the lack of effectiveness—when they tragically would have been better off trying a different approach or medication. How could a patient possibly give informed consent in such a scenario, for one thing? How could they meaningfully compare treatment options and make their own informed choices when the advice they receive includes lies?

Alas, some providers believe in placebo effects so much more strongly than their patients’ right to autonomy that when faced with complaints of side effects, they will just lie more and more to their patients in hopes that the side effects will go away, but that’s really just more gaslighting to people who are already in difficult situations.

Honestly, every time I look into if the "treatment by severity effect" is clearly established, I feel I come away only able to shrug. It is at least plausible, but hasn't been clearly established or refuted.

What does seem clear to me is that the whole cost-benefit considerations change in favor of anti-depressants when the depression is severe. I wouldn't say anti-depressants should be first-line treatments for ordinary depression, but for severe depression, I think they are a very reasonable first-line option.

Sure, they still might not help, but the costs / harms don't seem so bad compared to the potential costs / harms of leaving the severe major depression untreated, and the other options look all pretty terrible here too.

Clothes too. If you're cold, why not just move to a tropical country where you can be naked, as nature intended?

> I’m not trying to discount mental health, I just think there are better solutions than drugs to fix your state of mind.

Find one that's as effective on the general population.

I mean, sure, perhaps lifestyle changes are better. Can you get a higher percentage to change them and improve people's lives than we currently can with drugs?

As a top performer in school, I definitely think (and still point out), that you can get fantastically high results in SAT/GRE without paying any test prep service. I and many of my peers did it. There are better solutions than paying those services. But how many who don't pay do as well as those who do? I can tell them how to study as much as I can, but the reality is that statistically, people who attend will do better than if they don't.

From a medical standpoint, telling people to change how they live and think has a fairly low success rate. The best options usually don't work on the masses.

Agreed. They have to be significantly helping at least some, but we can't say who these people are for certain yet, or how many there really are.

And yes, in some cases, no other options are possible, so even if the evidence is pretty dismal for their effectiveness, they are still broadly safe enough to definitely be worth a try. They probably just shouldn't be the first-line approach.

I don’t get why people are so negative about drugs. They’re just a medical treatment, with pluses and minuses. If they help and they’re not too costly then what’s the big deal? Half the population is addicted to caffeine and nobody cares. A huge number of people need medical intervention for other things and we don’t get this quasi moralistic opposition to them.

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