Comment by whats_a_quasar | Hacker News Reader

Comment by whats_a_quasar | Hacker News Reader

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> This is not at all settled.

Yes, it is.

> For the people who believe it wholly, the effects that are claimed are marginal

No, the effects are not marginal. Research, the experience of basically all clinicians who prescribe antidepressants, and my personal experience all show they treat depression.

For a given person, an SSRI may significantly relieve their symptoms, have a mild effect, or have no effect. Across the population, studies of SSRIs consistently show they work to treat major depression [1].

Every clinician I've met has observed SSRIs being effective. They see depression symptoms getting better when medication starts, and they observe relapses when medication stops.

When I started taking Escitalopram, I stopped being depressed. When I stopped taking Escitalopram, I became depressed again. When I re-started Escitalopram, I stopped being depressed again.

My grandfather had the same experience. When he went on Citalopram, he became calmer and less irritable than he'd ever been in his life. He stopped taking Citalopram for a few weeks, because of a physical illness that interrupted a prescription refill, and immediately slipped back into a depression. When he went back on Citalopram in the hospital, he was smiling and singing again two weeks later.

[1] https://astralcodexten.substack.com/p/all-medications-are-in... https://astralcodexten.substack.com/p/all-medications-are-in...

The trouble is that the placebo effect has been repeatedly demonstrated to be extremely, profoundly strong for depression and anxiety treatments.

Yes research has found improvements when you put people on SSRIs, but double blind placebo controlled studies generally find that about 80% of the benefits also occur in the placebo group, so the actual benefit over placebo is only about 2 points on the HAM-D scale. [1]

On top of that, SSRIs have well-known side effects that are pretty noticeable for most people, so it’s hard to know how much of their benefit vs placebo is due to loss of blinding and/or the “active placebo” effect.

It is, however, notable that one study found a loss of effect when subjects were deceived and told that the SSRI they were given was an active placebo with similar side effects to an SSRI, and the differences were visible on brain scans, not just in their subjective reports.[2]

[1] https://journals.plos.org/plosmedicine/article?id=10.1371/jo... [2] https://www.nature.com/articles/s41398-021-01682-3

> When I started taking Escitalopram, I stopped being depressed.

Ooh, anecdotes, and ignoring your own quoted text, I can do that too!

When I started taking it, I became numb, lost my sex drive, and basically exacerbated my underlying anxiety problem related to the depression. When I stopped taking it, I had extreme, severe withdrawal symptoms, orders of magnitude worse than any other withdrawal I've ever been through. When I stopped taking it, I had been practicing meditation and going to therapy. I also threw in real commitment to the gym for the first time in my life. Took a while for the sexual side effects to wear off too. Needless to say, I have extreme resentment for the doc that put me on that with zero guidance, warning, options, etc. I know have a beta blocker prescribed that I can take to prevent the physical symptoms of anxiety from exacerbating into a mini panic attack, but I basically don't need to take those anymore.

I can find a non-trivial number of studies that (happy to link them, don't want to spam or be over the top right now), either:

1. Show it's barely more effective than a placebo.

2. Show it's barely more effective than a placebo, except for about 15% of those taking it, who had a measurable improvement.

I'm not a doctor but I'm going to sublty imply that there are other treatments for depression, with more impressive statistics, that don't cause bi-minutely head-to-toe "body zaps" when trying to go off it.

> For a given person, an SSRI may significantly relieve their symptoms, have a mild effect, or have no effect.

In other words, SSRIs do not work for everyone who has depression. For some people, they do; for others, they don't. You and your grandfather apparently are in the first group; but there are also plenty of people in the second.

Now comes the obvious next question: is there a way to tell in advance (i.e., without trying the SSRI on the person and seeing whether it works or doesn't) which people are in each category? No, there isn't. That's the impact of not knowing the mechanism: treatments for illnesses like depression are trial and error. If you find a drug that works for you, great! But many people never do.

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