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Comment by cdjk | Hacker News Reader

Prospective study was probably not the correct term, since that's an epidemiological study. "Placebo controlled study" is probably a better term. And a placebo controlled study is the best evidence for a medical treatment - doing epidemiological studies to determine medication effectiveness doesn't seem right.

Consider an SSRI study for depression. I want to know if someone who is depressed and takes it does better thank someone who is depressed and doesn't take it, or takes a different drug. I don't care what it does in a healthy population, since they probably won't be taking it. I mean, the effects of SSRIs in healthy individuals is an interesting topic, but not relevant if I'm investigating depression treatments.

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> And a placebo controlled study is the best evidence for a medical treatment ...

Yes, and with respect to the drugs we're talking about, subsequent meta-analyses show that the original studies were all biased in favor of their sponsors and all the drugs produce the same results, which argues for a massive placebo effect.

For years, studies were published that appeared to support various drug approaches to mental illness, but those studies have been invalidated by more careful analysis that included (as just one well-known example) unpublished studies that came to conclusions not favorable to the drug companies' outlook.

> Consider an SSRI study for depression.

Yes, let's do that. As things stand right now, studies of drugs that increase serotonin levels show the same effects as those drugs that decrease serotonin levels. This causes open-minded scientists to doubt the efficacy of this entire approach.

Reference: http://www.newyorker.com/online/blogs/elements/2013/09/psych...

Quote: "While S.S.R.I.s surely alter serotonin metabolism, those changes do not explain why the drugs work, nor do they explain why they have proven to be no more effective than placebos in clinical trials."

> I mean, the effects of SSRIs in healthy individuals is an interesting topic, but not relevant if I'm investigating depression treatments.

Such studies -- with the diagnosed depressed -- show no clinically significant result that can distinguish the outcome from the placebo effect. Those are the facts.

If SSRIs are no more effective than placebo, then:

* Why do some SSRIs work for some people while others don't?

* Why does increasing the dose of a specific SSRI have an increased effect?

Is it not possible that the real reason that SSRIs might be no more effective than placebo in clinical trials is that we don't quite understand the reasons that they work yet? (i.e. a specific SSRI might only have a real effect on 15% of the non-control group)

> If SSRIs are no more effective than placebo, then:

> * Why do some SSRIs work for some people while others don't?

The placebo effect. Surely you don't think everyone has the same placebo effect? Also, you're not describing the same study with the same participants and different drugs, you're describing different studies, different subjects, and different drugs -- all of which can change the outcome.

> * Why does increasing the dose of a specific SSRI have an increased effect?

The placebo effect. If people believe that a placebo is working, then more placebo produces more illusion.

Also, your use of the term "increased effect" is misleading. The largest doses show an effect, smaller doses show no effect. One theory about that is that the large-dose drug's side effects alert the subjects that they're not in the control group. A proposal has been made to create "active" placebos, placebos that mimic the side effects of the drug under test but not the property under test. This idea hasn't been tried yet.

> Is it not possible that the real reason that SSRIs might be no more effective than placebo in clinical trials is that we don't quite understand the reasons that they work yet?

You're overlooking the fact that placebos produce the same effects as the drugs under test. Our understanding or not understanding isn't an issue, because they've been demonstrated to be indistinguishable from a sugar pill.

And our not having a mechanism is definitely a criticism of this kind of treatment -- it would be like administering a mystery drug that proves essential to health, then deciding to increase the dosage, without understanding that the mystery drug is fatal in large doses (like vitamin A).

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