The background on this story is a community of science people found a bunch of unpublished studies that, when weighed with the studies which supported antidepressant approval, showed they were no more effective than placebo in mild-moderate cases.

Except unlike placebo, antidepressants express a wider range of severe side effects, like worsening depression and suicide.

Isn't this a scandal?  How do psychiatrists still prescribe these en masse?

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I would recommend a SSC post. You might also want to look at CrazyMeds.

Upvote for interesting and relevant links, although this part made me want to shout at my screen.

(9). Therefore, we should give up on medication and use psychotherapy instead Makes sense right up until you run placebo-controlled trials of psychotherapy ... Another study by the same team finds psychotherapy has an effect size of 0.22 compared to antidepressants’ 0.3-0.5

Even if this is true I don't agree with the cost-benefit analysis. Psychotherapy costs time and money but probably won't cause weight gain, sexual dysfunction and crippling withdrawal if you miss a dose or need to cycle off of them.

EDIT: I guess he says as much in a different article. Hmph.

This paper includes an interesting paragraph:

And noticing one of the listed side effects, would you not conclude that you had been given the real drug? In one study, 89% of the patients in the drug group correctly ‘‘guessed’’ that they had been given the real antidepressant, a result that is very unlikely to be due to chance

If that's true shouldn't we ask this question by default in placebo-blind trials?

Probably but the use and interpretation of blinding indexes is still a bit controversial. For example, the 2001 CONSORT guidelines suggested using and reporting a blinding index but the latest 2010 version dropped it, saying:

Item 11 (blinding)—We added the specification of how blinding was done and, if relevant, a description of the similarity of interventions and procedures. We also eliminated text on “how the success of blinding (masking) was assessed” because of a lack of empirical evidence supporting the practice, as well as theoretical concerns about the validity of any such assessment (23, 24).

The absence of the percentage of people on placebos who guessed that they had been given the real antidepressants suggests cherry-picking. Cherry-picking suggests the entire article is garbage.

Unfortunately the article they cite is behind a paywall, but the abstract includes this: "We studied medication guesses of 137 depressed patients and/or their doctors at the end of a 6-week randomized trial of placebo, imipramine, and phenelzine. Overall, 78% of the patients and 87% of the doctors correctly distinguished between placebo and active medication"

Assuming 1/3 were assigned to each group, and the majority of each group guessed they were on medications, the patient percentages are pretty close to what you'd expect anyways.

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From the paper:

Percent correct was 87% (34/39) for imipramine, 96% (22/ 24) for phenelzine, and 59% (22/ 37) for placebo.

That's more useful information.

That's significant at a 99% interval with a two-tailed test, so that's significant as far as I'm concerned. (I kept misreading that, and my first three or four calculations with that were assuming 22/37 placebo tests were guessing "Antidepressant" instead of "placebo", so it took an inordinate amount of time to get there. Did the same thing reading the abstract, actually. Teach me to read more carefully.)

Check out section 3 of this SlateStarCodex post.


’…William Potter, most recently Vice President of Translational Neuroscience at Merck Research Labs, Merck & Co., Inc., explained that a truly novel antidepressant has not been introduced in the last 40 years. According to Potter, the period of SSRI development established a level of comfort in the mental health community that may have temporarily hindered the development of new and better antidepressants. Today, significant effort is focused on understanding the challenges to developing novel antidepressant therapies and designing the informative clinical trials necessary to test the effectiveness of new discoveries…’

As for my personal story of antidepressants - they were okay, but mdma was better. Things don't have to be 'anti-depressants' to act to counter depression IMO. Reading over that MDMA LW chat log in retrospect is weird. I really wasn't taking in just about anyone elses agenda. It was all about me in my mind at the end. Empathy my ass! Though, thinking back to my MDMA experience (and the 'dada' song I listened to) gives me a happy default to return to when I'm upset, instead of say anger, detachment and sadness which I sometimes resort to.

My dentist consistently knows whether I've been brushing much or not, and when he does a cleaning it hurts a lot more if I haven't been doing it much. Also, after four or five days of not brushing my gums start to hurt, and they feel a lot better after brushing. That of course is consistent with e.g. the fact that you start to itch if you don't wash other parts of your body and so on. So that seems like good evidence that brushing is at least as useful as washing in general, even if it is only anecdotal insofar as that is my personal experience.


Dentists ability to predict whether you brush or not isn't evidence that brushing is better than not brushing at reducing undesirable outcomes, unless the undesirable outcome for you is your dentists chastising, rather than a negative health state

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You are correct Michael. Antidepressants don't seem to work better than placebo and yes it is immoral for psychiatrists to be prescribing antidepressants without enrolling the client in CBT (cognitive behavioural therapy). The medical model DOES NOT fit very well with mental disorders. A mental disorder is a bit like a peg leg, you can pretend you don't have a peg leg and take a bunch of valium to ignore the fact you have a peg leg but ultimately the best treatment for having a peg leg or a mental disorder is education and fancy this, teaching the client rationality techniques... Another big quam I have is how heavily valium is prescribed to people with anxiety disorders. The side effects of taking anti-d's which do not work or prescribing valium to an anxiety client includes death among other things. If the anti-d's do not work or the person with anxiety cannot control their own disorder without an anxiolytic the risk of something horrible happening is far higher. There is a problem here.

ps- yes I have done my research and am qualified to give my 2c worth (it is annoying you have to make these disclaimers on LW as this website seems to have spiralled in to the pits of navel gazing lately, i digress...)

Science is not that simple, I'm not sure you can draw such conclusions.

There was/is indeed a problem in the reporting of the evidence, that diminished the effect of antidepressant in the literature. Reporting bias is an important and serious matter in science.

That does not mean however that the antidepressant effects got down to a placebo effect. It seems that Kirsch does a lot of hand-waving to put aside the treatment effect. He did the same thing in 2008.

AFAIK the literature still says antidepressants have an effect better than placebo.

AFAIK the literature still says antidepressants have an effect better than placebo.

Do you have specific meta analysis in mind?

Even Kirsch's paper from 2008 results in that, and it's probably one of the most (or the most) harsh paper on antidepressants.

Patient care about improving, they don't care about improving compared with placebo.

In many cases a good psychiatrist tests multiple drugs to find the one that works for the client. The point of going to a psychiatrist is also that it's believed that the psychiatrist doesn't give you a random antidepressant but one that fits your personal needs.