> Now let's find out if this anti-depressant really helps anyone, or is it just another terrible drug with horrid side effects? If it doesn't help better than placebo; take it off the market?
The claim that SSRIs are no better than placebo is increasingly popular on the internet and among some researchers eager to make headlines, but the claim is not backed by the data. At best, it represents a misunderstanding of how the studies work, what they're showing, and how surprisingly effective placebo is in cases of mild depression.
> I do know drug companies have pretty much stopped all research in new anti-depressants. Why--they were caught with their pants down, lying, hiding bad studies, and fooling doctors and patients alike with their Slick claims.
This incident is deplorable and highlights a huge problem in our clinical trials process that needs to be addressed, but your extrapolations here not only don't make sense but they are flat-out incorrect.
There is quite a huge amount of research on new antidepressants. In the past few years alone we've added Vilazodone and Vortioxetine to our arsenal, both of which are primarily SSRIs but have some additional properties that might reduce the side effects due to requiring lower doses. We also have Levomilnacipran which is the first SNRI that favors norepinephrine over serotonin, which can be very helpful in some patients.
There are many interesting compounds in the pipeline as well, from rapid-acting compounds for addressing suicidal patients (ketamine infusion, esketamine nasal spray, GABA-A5 antagonists) to completely novel antidepressant compounds: opiod-modulating drugs like ALKS-5461 which have been very impressive in clinical trials, NMDA and sigma-1 antagonists, mGluR5 antagonists, NR2B antagonists, some very impressive BDNF modulators, anti-glucocorticoid strategies, and so on.
Contrary to your claims that "ruthless drug companies" have stopped all research, this is the most exciting time for anti-depressant research we've ever seen.
tl;dr: SSRIs have a substantial and clinically significant positive effect on patients with severe depression. The positive effect only decreases in patients with moderate depression, and becomes indistinguishable in patients with mild depression.
> Those graphs in the article look too close to placebo. So I wonder why antidepressants are still prescribed to treat any kind of disorder and not only, well, genuine psychogenic depression.
Another article goes deeper into this issue (ie. why do meta-studies show a statistically significant difference, but the difference is so small?)
> For some commentators, the recent downfall of the chemical imbalance theory has cast doubt on the use of existing antidepressant drugs, which were meant to restore the lost serotonin. Yet the data certainly suggests that they work better than placebos
I would argue with this statement. Antidepressants don’t work better than active placebos like atropine that make you feel “something is different” like dry mouth or elevated heart rate.
> the reason why many people mistakenly believe that SSRIs are effective for moderate and severe depression (as opposed to not effective for any type of depression)
I'm taking an SSRI now, after about ten years off, and have taken them on and off for more than two decades, and they most definitely have a dramatic effect on anxiety and depression - the effects and general mechanism are pretty obvious. Basically, emotional reactivity is reduced as well as the tendency to ruminate. For me, this effect is clear as day, as are why it causes the side effects that it does which is why I typically don't stay on them for very long. While they don't work for everyone, SSRIs have been enormously popular for at least two decades.
So I gather that you believe the entirety of SSRI's popularity, as well as all the good/bad physiological effects many of us taking them find so apparent, are strictly placebo effect?
> 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.
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.
> The "comprehensive" studies still show that SSRIs are effective
From the article:
"Most of the studies were supported by funds from pharmaceutical companies and were of short duration."
In other words, what they are saying is that the published research papers show efficacy for SSRIs, which is completely different from saying that the research shows that SSRIs are effective.
> Unfortunately, the pop-culture misunderstandings about "low serotonin" can mislead a lot of people into thinking that research like this debunks SSRIs. It doesn't. As I said above, we've known for decades that something else is going on. This isn't actually a surprise to anyone in the field.
The article itself quotes one of the authors of the study, who is attending medical school in psychiatry, as starting that his training explicitly made this claim, that his textbooks make this claim, and that he himself was later passing it down to other students.
Other sources quoted by the news article are similar to your own claims. Overall, it sounds like there are camps in psychiatry that have indeed long abandoned this theory, but others who still hold onto it.
Furthermore, the meta analysis being talked about in the article does make the additional claim that SSRIs are perhaps not necessary for the treatment of depression. I don't believe they are right, but it's also misleading to suggest that theur research is entirely in line with psychiatric orthodoxy.
> Recent research has indicated that Serotonin levels in depressed people are not lower than average. But SSRIs are effective for relieving depressive symptoms - either boosting serotonin levels above average works, or they work through some other pathway that hasn't been identified.
But that is exactly the point. If we don't know why something works, we can't even be sure that it does work.
Also SSRIs are only slightly more effective than placebo. [0]
Quote: "So, when we accessed the public domain data from the U.S. Food and Drug Administration (FDA) archives for the antidepressants approved between 1985 and 1997 (7), it quickly became apparent that many of the assumptions about the relative potency of antidepressants compared to placebo were not based on data from the contemporary trials but from an earlier era. Specifically, it became evident that the magnitude of symptom reduction was about 40% with antidepressants and about 30% with placebo."
Until/unless we can finally understand how the human endocrine system works, on both a broad statistical basis as well as on a predictable individual basis (i.e. in the same sense that statistically we know that X number of people die each year in automobile collisions but we don't know exactly WHICH people will die) we are making guesses.
The level of scientism our society exhibits - in which we cannot just accept that some things don't have answers that we can access at this time, and instead accept any answer "science" gives us - is unfortunate. Research we do is limited by what we look for, and the positivist approach we see in medicine ("Find diseases we can make money on") limits everything.
Quote: "Meta-analyses of antidepressant medications have reported only modest benefits over placebo treatment, and when unpublished trial data are included, the benefit falls below accepted criteria for clinical significance." (emphasis added)
Translation: "If all legitimate scientific studies of antidepressants are examined at once, the outcome is that antidepressants do not work."
Analysis: The drug industry has funded many antidepressant studies over the years. Those that support the efficacy of antidepressants are published. Those that do not support the efficacy of antidepressants are not published. It's a simple, effective scheme, and until now it has worked -- most people think antidepressants work.
The study linked above did something clever -- they performed a meta-analysis of all the studies -- those that were completed and published, and those that were completed and then thrown away. The end result is that antidepressants do not work, i.e. are no more effective than a placebo.
But because practicing psychologists don't care about science, this study might as well not have been published -- it might as well have been thrown out along with the many studies that cast antidepressants in a bad light, studies that were suppressed.
Someday psychologists will be forced to adopt the evidence-based practice standards that govern the practice of medicine, but until that day arrives, they will continue to lie to their clients.
> all antidepressants were more effective than placebo
Comparing them to placebo isn't appropriate, you need to compare them with an active placebo and only look at studies that continue longer than two years. Of which there are all of like 2 studies.
>Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory. But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect. Some antidepressants increase serotonin levels, some decrease it, and some have no effect at all on serotonin. Nevertheless, they all show the same therapeutic benefit. Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind. The serotonin theory is as close as any theory in the history of science to having been proved wrong. Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.
> 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.
The seratonin theory of depression was recently debunked and SSRIs shown to be no better than placebo
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