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PaperclipPerfector  11mo ago (text post)   2819 thread views

Wellness Wednesday for November 22, 2023

The Wednesday Wellness threads are meant to encourage users to ask for and provide advice and motivation to improve their lives. It isn't intended as a 'containment thread' and any content which could go here could instead be posted in its own thread. You could post:

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  • Encouragement. Probably best directed at specific users, but if you feel like just encouraging people in general I don't think anyone is going to object. I don't think I really need to say this, but just to be clear; encouragement should have a generally positive tone and not shame people (if people feel that shame might be an effective tool for motivating people, please discuss this so we can form a group consensus on how to use it rather than just trying it).

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I've bounced between a few SSRIs and SNRIs in my life, but haven't seen much difference other than the fucked-up sex drive.

Are you certain they didn't make things better? I had to go on and off of SSRIs and SNRIs like 4 times before I finally accepted that it wasn't coincidence that better things seem to happen to me when I'm on them, and worse things seem to happen when I'm off them. I really thought it was coincidence at first, but eventually realized that I notice and accept the better things when I'm on these drugs.

This is a valid point. For what it's worth, I do notice an immediate and marked decline in my mental functioning if I ever forget a dose or skip one. It's subtle, but I've had it happen several times where I forgot to take it and then, like 12 hours later, realize I've been way more anxious than I normally am. I am suspicious that this is just a withdrawl -- let's call it what it is, and not use euphemisms like "discontinuation syndrome" -- that I would recover from if correctly tapered off. That's why I haven't discontinued the medication at this point.

However, I don't notice an overall difference in mood now vs before I started medication. I think the emotional blunting probably has some impact in "taking the edge off," but not enough for it to be a major improvement that helps me function more normally. I don't think it's pure placebo, but I also don't think the size of the effect is large enough for it to be worth the drug dependence and side effects.

Not OP, but I tried 3 SSRIs and 1 SNRI and they didn't help in the least.

I definitely believe both you and OP that there are probably people for which these drugs have no effect. But I also think it's worth doublechecking, since I definitely had my aforementioned experience.

SSRIs have pretty weak effect sizes, but that's not the same as them being entirely useless after all.

Thankfully, Scott has a deep dive on the subject, sparing me the trouble:

https://slatestarcodex.com/2018/11/07/ssris-an-update/

All this leads to the third thing I’ve been thinking about. Given that the effect size really is about 0.3, how do we square the scientific evidence (that SSRIs “work” but do so little that no normal person could possibly detect them) with the clinical evidence (that psychiatrists and patients often find SSRIs sometimes save lives and often make depression substantially better?)

The traditional way to do this is to say that psychiatrists and patients are wrong. Given all the possible biases involved, they misattribute placebo effects to the drugs, or credit some cases that would have remitted anyway to the beneficial effect of SSRIs, or disproportionately remember the times the drugs work over the times they don’t. While “people are biased” is always an option, this doesn’t fit the magnitude of the clinical evidence that I (and most other psychiatrists) observe. There are patients who will regularly get better on an antidepressant, get worse when they stop it, get better when they go back on it, get worse when they stop it again, et cetera. This raises some questions of its own, like why patients keep stopping antidepressants that they clearly need in order to function, but makes bias less likely. Overall the clinical evidence that these drugs work is so strong that I will grasp at pretty much any straw in order to save my sanity and confirm that this is actually a real effect.

Every clinician knows that different people respond to antidepressants differently or not at all. Some patients will have an obvious and dramatic response to the first antidepressant they try. Other patients will have no response to the first antidepressant, but after trying five different things you’ll find one that works really well. Still other patients will apparently never respond to anything.

Overall only about 30% – 50% of the time when I start a patient on a particular antidepressant, do we end up deciding this is definitely the right medication for them and they should definitely stay on it. This fits national and global statistics. According to a Korean study, the median amount of time a patient stays on their antidepressant prescription is three months. A Japanese study finds only 44% of patients continued their antidepressants the recommended six months; an American study finds 31%.

Suppose that one-third of patients have some gene that makes them respond to Prozac with an effect size of 1.0 (very large and impressive), and nobody else responds. In a randomized controlled trial of Prozac, the average effect size will show up as 0.33 (one-third of patients get effect size of 1, two-thirds get effect size of 0). This matches the studies. In the clinic, one-third of patients will be obvious Prozac responders, and their psychiatrist will keep them on Prozac and be very impressed with it as an antidepressant and sing the praises of SSRIs. Two-thirds of patients will get no benefit, and their doctors will write them off as non-responders and try something else. Maybe the something else will work, and then the doctors will sing the praises of that SSRI, or maybe they’ll just say it’s “treatment-resistant depression” and so doesn’t count.

In other words, doctors’ observation “SSRIs work very well” is an existence statement “there are some patients for whom SSRIs work very well” – and not a universal observation “SSRIs will always work well for all patients”. Nobody has ever claimed the latter so it’s not surprising that it doesn’t match the studies.

This is 2018, pretty sure the "SSRIs are a placebo" thing came out after that.

I strongly disagree, I'm quite confident it was a relatively mainstream argument well before 2018, Scott wrote a post in 2014 to which this serves as an update, and that was partially motivated by the claims that SSRIs were useless/placebos.

Edit: The placebo theory is clearly mentioned in the text excerpt I posted as well as in his original blog post.

I mean that there was some big meta-analysis released a lot more recently than Scott wrote his article, which got a lot of press coverage. I think it was this one but I'm not 100% sure.

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