The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT, effect size or remission rate (individually! STAR-D treatment algorithm works for the vast majority of people)

Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity, especially since some minority of major depressive episodes resolve spontaneously after a few months to a year.

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Aurornis 9 hours ago | parent | next [-]

> The other problem with SSRI treatment is that individually they are only barely better than placebo. They're among the worst classes of drugs as far as NNT,

These numbers are really misunderstood when taken out of context.

SSRIs have an NNT around 7, depending on the study you look at (random Google result https://pubmed.ncbi.nlm.nih.gov/19588448/ as an example )

Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy.

> Especially in acute cases, I think they should be replaced or augmented by something stylistically in the direction of esketamine. 6-8 weeks per medication trial is an absolute eternity

Ketamine and esketamine are used a lot to begin therapy. They’re not good long-term options though, so they’re best used to start treatment as a bridge to SSRI efficacy.

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D-Machine 3 hours ago | parent | next [-]

> SSRIs have an NNT around 7, depending on the study you look at [...] Which sounds terrible if you know nothing about NNT. But when you learn that Tylenol has an NNT of almost 5 and even a powerful drug like Xanax has an NNT of 4, you realize that NNT is a difficult measure of drug efficacy

This kind of comparison is utterly meaningless (like saying a Cohen's d of 0.3 is large for phenomena X, so if we see 0.4 in phenomena Y, it is large in Y), and is just one part of why NNT as usually reported is basically deceptive for antidepressants.

What qualifies as an effective "treatment" has to be anchored to a minimal important difference, and this is what antidepressants really don't clearly have, on average. I.e. saying the NNT of SSRIs is around 7 is not really practically interpretable, because they tend not to base NNTs here on the amount of patients that actually experienced a clinically meaningful change, they just count the number that exceed some arbitrary (usually purely statistical) threshold.

If you reformulate NNT competently to count number of people needed to be treated to ensure one has (on expectation) a minimally important difference in the depression scales, then the NNT gets even larger than is typically reported.

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jaggederest 9 hours ago | parent | prev [-]

Okay, so we set aside NNT, even though their NNH is also quite low, and that's highly relevant, what about effect size and remission rate? This feels a bit like cherrypicking. And you'll note I said "augmented", as well, if somebody is going through the treatment algorithm with SSRIs, by all means, that's the bridge to stability for somebody on a longer term course.

But many people don't need anything more than acute treatment, so what about them?

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Aurornis 9 hours ago | parent [-]

> what about effect size and remission rate? This feels a bit like cherrypicking

Trying to pull out NNT feels like cherry picking because it sounds really bad to people who don’t know how other drugs look on this measure.

If your point is that it would be better if we had better drugs then I agree.

I think trying to imply that SSRIs are barely a step above useless is not helpful, though. Statistics like NNT and remission rates do not capture incremental improvements that these medications can make for people who need all the help they can get. Even if it doesn’t cause complete remission by itself it can be very helpful.

	▲	jaggederest 3 hours ago \| parent [-]
		> If your point is that it would be better if we had better drugs then I agree. My point is that there are other interventions which do have an effect size over the perceptual threshold. Exercise is a big one, but there are lots - sleep deprivation, intensive therapy, the esketamine class, TMS, ECT in extremis, (nature exposure and other seeming woo like that need study but are promising) are all significantly better than handing someone an SSRI. And many of those don't have the withdrawal symptom and side effects under treatment that SSRIs do. People are, in aggregate, being harmed by SSRIs displacing things that work right now, and also displacing the urgency of new drug development in the space. The gap is that, in an acute treatment setting, people are being handed a drug that cannot be effective for at least a week or two, up to 6-8 weeks, instead of drugs that work in hours or days.

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MrDrMcCoy 9 hours ago | parent | prev [-]

+1 on therapeutic ketamine. Got me out of a bad spot, and felt better long after it was over. You can get it by mail in the US from Mindbloom, who offered excellent care despite being remote in my case.