> 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.
> 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.
This is not something you can claim. How could you possibly know that the SSRI is responsible for your recovery?
I'm not going to say that antidepressants are useless, but it is important to understand how placebo works. The key point is that placebo works and it is impossible for an individual to distinguish between a placebo and a life changing drug.
In antidepressant studies, SSRIs often outperform placebo to a degree. However, the placebo group has an excellent recovery rate! That means there are people who are clinically depressed, suicidal etc. who are then given a sugar pill as part of a study and make a full recovery.
>You often need to try 2 or 3 different SSRIs
That makes it even murkier. SSRIs take a long time to work, and if you try several of them that's going to take months to years. There's a high probability that in that time, you might naturally recover. You have the combined benefit of placebo and waiting in addition to the effects of the SSRI. You tried 2 SSRIs that didn't work. What makes you so confident that it was the third?
Again, I'm not saying SSRIs are useless. But it's important that we rely on controlled studies to make these determinations. Personal experience and anecdotes are beyond worthless; for example they are the reason why homeopathy is a $20 billion dollar industry even though it is actually provably useless.
> If you think that SSRIs don't help people then you simply don't understand what a true and chemical despair feels like.
Or you read? If SSRIs are so helpful, then why does the majority of the research suggest that this isn't the case?[1] If you think they are helpful, then the burden of proof is on you to show that the science is incorrect.
> We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo.
> 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.
> 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.
> Even WITH the unpublished studies included, the placebo effect far exceeds the required effect size to be considered clinically effective which means that the combination (placebo effect+treatment effect) also far exceeds the required effect size.
This is astonishing. The paper in question flatly contradicts you. The paper concludes, "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."
The above conclusion is not open to the interpretation you've given it.
And, in case you missed the train leaving the station, none of this will matter until some science is done -- science that uncovers the cause of depression and ends this guessing game and debating society.
> I wish people would stop saying online that SSRIs are a scam.
Some people like their SSRI's, some people kill themselves soon after starting that class of drug [0] (presumably due to the serotonin syndrome [1]).
> My life was saved by Lexapro, an SSRI.
My friend told me about how Lexapro seemed to help her. But it also didn't keep her from relapsing on cocaine, a pro-dopamine drug. The MAOIs are much more useful for a cocaine-like boost that doesn't make them crash after 20 minutes than the SSRIs, which take weeks/months before most people notice any benefit, and which help some people by helping them "not care" about their life situation.
> If you need help don’t get spooked by the parent commentator. Help exists.
My observation is that some people don't actually get the help they need, and deteriorate from defective prescriptions. My friend needed help getting her drinking under control, but all she got was medically assaulted with anti-dopamine drugs (so-called "antipsychotics").
The tragedy is that we actually know how to help people. Some of the MAOIs are much better drugs to use temporarily while helping people deal with "stress".
> All of that changed after going on Prozac. I don't know why, and I've heard from many others that Prozac was harmful to them.
SSRIs are some of the most widely-used medications. Tens of millions of people in the United States alone use SSRIs regularly with good results.
No medication is perfect, obviously, and at scale we're bound to see a percentage of people have negative experiences. The problem is that when tens of millions of people have tried SSRIs, even 1% significantly negative reactions adds up to a very large number of people. If 1% of those negative reactions make a point of blasting their negative experience all over the internet, we'll see thousands of negative reports everywhere.
Combine this with the fact that few people are willing to publicly admit that SSRIs helped them, and the bias toward negative reviews online is huge.
SSRIs are a particularly difficult topic, because they have a noticeable treatment lag (can take up to 1-2 months for positive effects, with positive effects increasing up to 6 months out) and can, in some cases, temporarily worsen symptoms during the initial ramp-up period.
Even more difficult, not all SSRIs are the same. It might take 2-3 trials before someone finds the SSRI that works best for them. It might also take several dose adjustments to find the right tradeoff between efficacy and side effects. Unfortunately, many people go online and seek out horror stories before they have a chance to go through a few rounds of medication adjustments to make it work for them.
Thanks for sharing your positive success story online. SSRIs aren't for everyone, but it would be a shame for people to spend years suffering from depression when a few SSRI trials might reveal an easy improvement to their lives. Worst case, they can taper off (tapering helps avoid discontinuation effects) and move on to different treatment avenues.
> Research suggests antidepressants work only a bit better than placebos
That really undermine the credibility of that article. They work extremely well for some people. Others might need to try several before they find one that works. And a minority might not be able to find one that works (I don't know, I'm not a professional).
Another anecdotal evidence: I started taking anti-depressants 1.5 months ago, and after the acclimating period (which was hell for me, I wish I had been better warned, I had to take a week off), it's a night and day difference on how my brain works.
My SO had the exact same experience: it changed her life, from a miserable struggle every day to a life she can enjoy.
If this article makes you reconsider taking anti-depressants or not, please talk to a healthcare professional instead.
> Believe me, if there was a placebo-based solution to this, I would be the first person in line to get it...
If you are taking drugs for this, then you are in line already. Every one I have read about has studies showing it is only slightly more effective than placebos.
I really am not trying to say the problem is not real. I'm only saying that placebos are far more effective than you realize.
For example some quotes from wikipedia:
"Notably, however, a recent Cochrane review of the efficacy of the SSRIs concluded that they were only slightly more effective than placebo for the treatment of people with depression."
"A widely-reported meta-analysis combined 35 clinical trials submitted to the U.S. Food and Drug Administration (FDA) before licensing of four newer antidepressants (including the SSRIs paroxetine and fluoxetine, and two non-SSRI antidepressants nefazodone and venlafaxine). The authors found that although the antidepressants were statistically superior to placebo they did not exceed the NICE criteria for a 'clinically significant' effect. In particular they found that the effect size was very small for moderate depression but increased with severity reaching 'clinical significance' for very severe depression. The relationship between severity and efficacy was attributed to a reduction of the placebo effect in severely depressed patients, rather than an increase in the effect of the medication."
(Especially note the last sentence.)
Please don't understand this in reverse and assume people should/can do nothing. My point is placebos work, and people should make more use of them.
Another thing: just because something is all in your head does not mean it's not real. People often assume that "since a placebo fixed it, it was not real to begin with". NO! That's is NOT the case. The problem was REAL, and the placebo fixed it.
>It's shocking to me how few people realize that anti depressants very rarely outperform placebo
very rarely?
>Findings
>We identified 28 552 citations and of these included 522 trials comprising 116 477 participants. In terms of efficacy, all antidepressants were more effective than placebo ...
> 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.
> 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?)
> Making blanket generalisations when it comes to mental health is extremely reckless and misinformed.
The SSRIs are modern snake oil. I gave a reason why they seem to work for some people. Other people think that they're helped, but really their SSRI has only helped them "not care" about circumstances in their life that they're not happy about. I've posted this link in earlier comments.
> Doctors aren't in the business to kill people.
Pharmaceutical companies are in business to pay dividends to their shareholders. Their researchers are employed to make new patent drugs, not to figure out fundamental causes of disease. For these businesses, killing people is par-for-the-course: not the ideal outcome, not unexpected. Doctors' credibility is just collateral damage.
> SSRI do save lives. We just know they kill a tonne of people as well.
Robert Whitaker disagrees with you - he's found that, over the long term, most psychiatric medications are very harmful. Look at his website [1], read his books, and get back to me with specific reasons why he's wrong.
> We just have a currently useful tool to help, SSRIs.
Yes, but the quoted study shows that serotonin and depression aren't correlated. If that is so, if the study bears up under scrutiny, then SSRIs cannot possibly work. The prior FDA meta-analysis shows that SSRIs don't work for the majority of patients, this new study explains why.
> Maybe with these type of studies we'll see more accurate medicines.
Let me suggest an alternative -- instead of searching for a better description of depression, we should seek an explanation, like in science. Armed with an explanation, we could treat depression's causes, rather than its symptoms.
But we can't do this with psychiatry -- psychiatrists aren't scientists and have no respect for evidence.
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.
Scott Alexander has already done a great job debunking these claims: http://slatestarcodex.com/2014/07/07/ssris-much-more-than-yo...
> 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.
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