Antidepressants Work No Better Than a Placebo

Matthew Whalley writes "Researchers got hold of published and unpublished data from drug companies regarding the effectiveness of the most common antidepressant drugs. Previously, when meta-analyses have been conducted on only the published data, the drugs were shown to have a clinically significant effect. However, when the unpublished data is taken into account the difference between the effects of drug and placebo becomes clinically meaningless — just a 1 or 2 point difference on a 30-point depression rating scale — except for the most severely depressed patients. Doctors do not recommend that patients come off antidepressant drugs without support, but this study is likely to lead to a rethink regarding how the drugs are licensed and prescribed."

Further evidence...

A while ago somebody noticed that anti-depressant drugs don't work at all unless they have some side-effects. The side-effects remind the user that he or she is taking a wow-must-be-powerful drug, which increases its placebo effect. The upshot is that it is completely counterproductive to search for an anti-depressant drug that has no side-effects. In fact, the more side-effects the better.

I don't remember more details than this, though.

In any case, it reminds me of a similar effect in microeconomics, in which consumers would tend to evaluate a widget more favorably if they had paid more money for it.

Depression is not all serotonin

I was on Zoloft for a couple of years way back when I was a teenager. It did fuckall to help my depression, I still hated life and still contemplated suicide, but I noticed something funny after I stopped taking it (due to severe gastrointestinal side effects). A few days after I'd quit the pills cold turkey, I was thinking of something I was stressed about, and along with the common wave of emotional despair, felt a physical sinking in my chest that I realized I hadn't felt for... about two years. I laughed when I realized that that was probably the chemical reaction that the SSRI had been halting, and laughed harder the longer I contemplated what a drop in the bucket it was in the scope of the depression I was struggling with. It made me understand the extent to which the Zoloft was just targeting a symptom of a larger problem, like any number of other medications do. There may be some people whose depression truly does stem from such a one-note imbalance, and I truly hope that the medication can help them, but it doesn't surprise me that antidepressants could be so insignificant to so many others.

Quitting "Cold Turkey"

"A few days after I'd quit the pills cold turkey"

Just a note - whether or not you think your pills are helping you, don't try this. It's extremely dangerous with most medications. I'm not posting to berate the Parent, just letting others know that it's a really bad practice that can lead to serious consequences with a lot of these drugs.

Eli Lilly CEO

I just listened to the CEO of Eli Lilly speak for an hour last night, and he said most prescription drugs work at best in 80% of patients who are diagnosed with the disease it's supposed to treat. Their least effective drugs only treat 20% of patients. Until effective genomics, proteinomics, and metabonomics testing systems come out, which will show exactly how people react differently to drugs, they have to train doctors in choosing criteria where the drug will work, and ensure that they don't prescibe drugs that don't work in that circumstance. Selling drugs that don't work is an unsustainable business policy.

He talked about Strattera, a nonstimulant ADHD drug, that works works best in people with ADHD combined with clinical anxiety. Otherwise, the patient should be prescribed a stimulant based ADHD drug, which works more often in other cases.

Anyways, a lot of drug trial data is needed to find the population where the drug works. In a lot of cases the drug might not work at all. Prescribing methicillin against methicillin-resistant Staphtacaccous aureus will probably an efficacy similar to placebo.

(SIGH) that figures

(SIGH) nothing ever works, its hopeless!

Anafranil

I don't know about deep depression, but with rather mild depression I took a 25mg pill of Anafranil and had some 2 days of pretty much silly euphoric high.

The effect wasn't mild or insignificant or anything you could consider effects of placebo. I was feeling like in very good mood, work that felt like dread before, could be finished at my standard efficiency and the effects were NOT negligible.

Of course there -were- side effects and they were quite strong (feeling of heat, including sweating and problems with sleep, lower max physical strength, getting physically tired faster, problems with urination), but first they felt like a total non-issue due to the great mood I was in, and second, the lower efficiency of my body at physical work was ballanced by increased enthusiasm and will to work more and mental efficiency was not affected (not just in subjective opinion) and no other factors of perception than general very good mood were affected (although feeling far too warm to fall asleep resulted in natural effects of insomnia).

No idea what drugs they talk about but Anafranil is THE shit :)

The wrong med from the wrong dr.

Sorry, I have a considerable amount of experience with family members who went the counseling route for years without seeing improvements. After finally deciding to try anti-depressants, anti-anxiety, etc., the problems they had most of their lives went away or were reduced to levels that made it easier for them to have a better life. The biggest problem I've seen is not whether they work or not, it's that GPs are the ones issuing the Rx. GPs are just that - GENERAL practitioners. The good ones admit that their knowledge of the nuances involved with the "low-level" chemical behavior of the brain is limited. A psychiatrist, someone with a medical understanding of the topic (not knocking psychologists, but their understanding is in a different area: the non-biochemical causes of issues) should be the person making the determination of just what a person should be on. They're aware of more of the potential "cocktails" of drugs (one particular drug is not enough) - both in terms of what works and what needs an additional medication to target secondary causes/effects of depression....

Missing the point

The point is not that antidepressants don't work - the point is that diagnosis criteria for depression has been to lax for too long. "Everybody gets depressed, not everyone needs antidepressants" It makes sense that the only people who respond to antidepressants designed to fix chemical imbalance are the ones with severe depression.... who are likely to have a real chemical imbalance. These are not "happy pills" they are formulated to fix an insufficiency. Normal, mild depression from events (death, divorce, etc) has always been treated best by cognitive behavioral therapy (aka psych visits), unless you just want to zonk someone out. But, in our society, if you have a problem you get a pill. No one wants to hear "go talk to someone and get over it," so doctors write the scripts and the generally malcontent get them filled.

Grossly misleading headline

Seriously, Slashdot editors: be a bit more responsible when you are dealing with potentially serious and life-threatening medical conditions. The study did not find that "Antidepressants work no better than a placebo". What it seems to have found is that there is an indication that antidepressants do work for people who do have a serious depression, while there is little indication it works better than a placebo for lighter (possibly misdiagnosed) cases.

Here's the thing: a clinical depression is a serious, crippling condition. Recent research has tied its physical underpinning to a slowdown in neurogenesis in certain areas of the brain. Most likely, this slowdown is caused by the bad quality of sleep caused by continuous and prolonged stress. But whatever the cause, the end result is a brain that is physically different. Yes, this is a physical condition, one whose recovery is progressive and takes a fair amount of time. And it's precisely in this condition that antidepressants have been shown to be of help. Moreover, you cannot magically cure someone with a clinical depression by having them "snap out of it". (Would you say "snap out of it" to someone with a broken leg?)

Part of the reason why depression is so wildly misunderstood is because everyone gets the blues every now and then. That is not the same as a clinical depression. And if a misinformed doctor prescribes antidepressants to someone who just has this "pseudo-depression", then it's no surprise that antidepressants won't really make much of a difference. However, this does not invalidate that antidepressants are valuable tools in fighting real clinical depressions.

Re:Grossly misleading headline

Well put. Depression, because of it's overlap with "normal" human experience, is wildly misunderstood. Most people never experience psychotic symptoms, so they don't harp as much on the utility of antipsychotics, or, by the same token, anti-seizure meds for epileptics. They *do* feel bad from time to time, and so they feel they have depression figured out. Perhaps it's the fault of GPs who diagnose those people with depression, thus reinforcing their belief that depression is exactly what they've experienced.

Clinical depression is a world apart from "a bad month." It can cause hallucinations, anorexia, insomnia, profound fatigue, sensory disturbances, and inability to think. It's a physical disorder, and generally the physical symptoms precede the subjective ones (sadness, apathy, suicidal ideation).

I agree that it's normal for most people to get in a funk from time to time, but usually that's situational - your dad dies, you move somewhere new, you lose a job. I also agree that it's possible to use therapy to help instead of drugs, if your problem is due to negative/erroneous beliefs and self-narrative.

What I don't agree with is the herd mentality to throw out antidepressants due to an erroneous conception of the disease and the proper use of medications. The first antidepressants were discovered accidentally, by doctors treating tuberculosis patients with Iproniazid [wikipedia.org]. The patients' moods changed enough that it was obvious something was going on. This wasn't anticipated, and thus certainly wasn't a placebo effect.

There is a reason why studies go unpublished

Disclamer first, I work for an R&D company that develops interactive voice response systems (ie: phone surveys) that are used to apply traditional depression and mental health tests in a consistent manner. My company is in part funded by grants and projects paid for by large pharma comps. Although I personally have no contact with them.

When pharma's want to do a study, they set up sites, each site will have one or more doctor and each doctor will have one or more patient who is participating. Quite often, these studies pay a bonus for each patient up to the quota, or the docs will want to try to help and fill their quota. When they do this, it introduces people into the programs who really should not be there. It's not that they are being purposely decietful or anything, they just aren't being as consistent and strict as they should be. I know this to be a fact, we have done numerous studies in which our system's performance is compared to real world docs across the US. And each and every time, our system would exclude over 20% of the patients that the doctors would enroll.

Since these studies are being poluted with people who do not reach the level of condition the drug was ment to treat, the drug will be ineffective on them. You can't "undepress" people who aren't depressed to start with. So they will reduce the effective correlation of the drug. There is also another natural bias that clinicians apply that causes a deflation of scores at the end of the study due to the double blind factor being eliminated by side effects.

In short, traditional ways of performing these studies are heavily flawed and will often result in a lower apparent effectiveness than the drug actually has.

-Rick

Required supplemental reading

Everyone needs to read the Last Psychiatrist's article [thelastpsychiatrist.com] on this study. He's a forensic psychiatrist, and a great blogger, and he makes some very interesting points:

It's the exact same data they had 10 years ago, the exact same data. This isn't a discovery, this isn't Woodward and Bernstein, this is a bunch of academics who are no longer on Pharma payrolls who have now decided that they have nothing further to gain from pushing antidepressants.

Now they can pretend to be on the side of science. We reviewed the data, and found some of it was not published.

You knew that already. You were the ones who didn't publish it [thelastpsychiatrist.com] -- it's your journal. Turner worked for 3 years as an NIH reviewer. He just notices this now?

Is no one wondering how it is that this study comes out now, when all antidepressants but two are generic?

As suspicious of Pharma as everyone is, no one seems to see that they are no longer getting Pharma money, they are now getting government money-- NIH-- so they're going to push the government line. No one finds it at all suspicious that the two biggest NIH studies in the past two years both found the generic to be the best?

You think that in 2000 those studies would have been published? But now-- 2007, 2008, if they'd found Cymbalta to be the best on the NIH's dime, you think that they'd get re-funded? What's the difference? Same authors, same studies, same data. All that's changed is the climate.

People want a direct financial link to show bias, not realizing that bias is much more prevalent and more powerful elsewhere.

The Black Dog

A close relation in my family has suffered from depression for well over 10 years, it is a tragic malady and it has an effect on the people around him. His diagnosed conditions include Manic depression, Psychotic episodes, Paranoia and auditory hallucinations, but worst of all when you are around him you can sense the terrible sadness that afflicts him. He has regular visits to a Psychiatrist to assist him.

Amongst the side affects of the many drugs that are prescribed, he has become overweight and now suffers from sleep apnea further complicating the depression. If anything I have learned from observation is that people suffering from depression need the support of people close to them, for the condition is like a downward spiral of physical, mental and spiritual decay. Contact, phone calls conversations, anything you can do to help unravel the root cause of the depression, like challenging the paranoid feelings all help to take power away from the disease.

For the fist time in a long time, I think I see him finally come out of it because he is starting to excercise. I don't know if the drugs helped, perhaps leveled things out and maintained the status quo. They were probably required as on several occasions I was physically attacked by him (and he is a big guy), fortunately for me (and him) I also am a big guy and have trained physical combat for most of my life. I say that because there was a strong responsibility on my part to not hurt him any more than it was required to control and disarm him. You have to realise it's not the person attacking you, it's the disease and for this reason I think that it is also can become contagious (so to speak) who do not have this capability.

I can't say whether the drugs are good or bad (just that there is a lot of them and he takes them e-v-e-r-y--d-a-y) but I do know the drugs have changed his brain chemistry forever, I often wonder if the person I grew up with is still in there, occasionally I see a glimpse. I have studied all I can about depression to learn everything I could to help him and I look forward to reading about other peoples experiences in this discussion. What I learned is that the medications are a commitment for all the people around to be aware that the critical time is when they are coming off the medication and they finally lose their apathy towards self harm, i.e they finally have enough energy to do it, signs that must be watched for if you want someone you care about to actually survive depression.

I also learned that regardless of the drugs there are two core issues that every person who suffers depression will have to face;

1) Rigorous physical excercise is that path back to mental well-being, the sooner the better and something fun and positive that helps self esteem and confidence.

2) The issues that triggered the depression will eventually have to be faced.

I hope one day it will be gone, because I don't want my family member to die from it or with it. I call it the black dog because it chases and hunts you down and occasionally I sense it coming after me, but I fight it and you have to fight it. Perhaps if people who were susceptible to depression were made to excercise it would disappear, but then the drug companies wouldn't get to sell all that expensive medication and I definitely think it is a factor in the diagnosis of this modern curse. I also think that good spinal care is a factor as I also noticed an improvement in his demeanor when this was done. Additionally I think that depression is a natural consequence to some overload of emotional stress, alas IANAP, that triggers a change to the brain chemistry.

I suspect the Metalica song Until it sleeps [google.com.au] was written about depression as it aptly describes what is truly the modern plague of our time.

Re:This just in!

Spoken by someone who's obviously never suffered from depression.

Re:This just in!

What? It's a placebo? AAH DON'T TELL ME!

*plugs fingers in ears*
la la la la la

Re:This just in!

Just like you can decide not to feel pain when someone hits you, right? I mean all the beating did was send a bunch of electrical signals into your brain. Pain itself is all in your head.

Re:This just in!

No, seriously, he's right. It's not so simply like you can just say, "I'm not going to be depressed" but just being depressed is itself a real downer than sucks you in deeper. Antidepressants, even if they only work through placebo affect, provide a patient with hope, which could help the roller coaster move gradually upward.

The best days are usually the days you've made a plan of action and convinced yourself it will change everything and you'll be better--you're thinking positively and not fixated on your depression. The worst days are when you realize you plan of action didn't do shit and everything still the same.

Re:This just in!

It's funny, I used to be among the camp of people that would say "just make yourself be happy". For me it was really that simple. Anytime I was in a bad mood I could just will myself out of it and simply could not understand other people that couldn't.

That was of course until I started taking steroids [webmd.com], no not the shoot 'em in your ass and get big kind, the prescription kind. Now a normal dose for this drug is 5-10mg usually given for skin problems and sometimes for asthma. The bottle specifically states that you should not suddenly stop taking this medication and there needs to be a weening period to help you get off of this drug. The dose I was given was 120mg that I was instructed to start on the first day of the month, take for 5 days and then stop altogether. The goal was to try to make my immune system recover from months of intensive chemotherapy. After the second day of taking this medication, my mood could only be described as extremely optimistic about everything and a view that I was, for the most part, wholly invincible. This feeling lasted until the sixth day at which point I had stopped taking the drug and started to feel like the world was literally crumbling around me. I would see a commercial on TV and start to cry when I realized that I do sometimes get that 'Not so fresh feeling'. It was ridiculous. At one point I got into an argument with an old friend who did not know what I had been going through, and for a moment considered jumping 3 stories to my death so she could see how much she hurt me.

It was at that moment that I realized what true depression was. I looked back on the moment a week later after the side effects had dithered and thought about how irrational those thoughts were. At the time when I was having them however, they seemed a perfectly logical solution. Now I realize this is an extreme case brought on by side effects of a powerful drug, but it does represent to me how an unbalancing of chemicals in the brain can greatly affect a persons mood and I will never again jump to the conclusion that a persons depression is not affected by a real problem with their physiology.

With regards to the placebo effects of anti-depressant drugs, I will say that at one point I was prescribed Lexipro by my doctor for what at the time was really situational depression. This drug was certainly no placebo. While it did not make me happier, it had the affect of making me extremely anxious and angry. I developed very violent tendencies over the 2 weeks I was on it. This drug was obviously mis-prescribed by a bad doctor, but it most certainly altered my brain chemistry. My cousin, who is more similar to me that our parents are to each other (sisters), was prescribed the same drug with very similar effects. So there may be some drugs out there prescribed for depression that don't work for a lot of people, and others that have unintended effects, but this may be due more to doctors not understanding the illness of their patients and not understanding the drugs intended uses.

Re:This just in!

If someone has real severe clinical depression, drugs are the only scientifically proven way to get back to leading a normal life.

Yes, this is not under dispute

The research does in fact say that for the most serious cases of clinical depression, the drugs do have a benefit. They don't work any better in such cases you understand; it's just that the placebo effect drops away sharply at the extreme end of the severity curve, so that drugs become more effective by comparison.

The point here is that for the vast majority of cases where the four anti-depressants in question are usually prescribed, they have roughly the same effect as a couple of grams of chalk wrapped up in a sugar coating. Which rather brings into question their value in all but the most extreme cases.

[ Info based on an interview on Radio 4's Today Program, this morning. They had an interview with one of the researchers, and another with a rep from the drugs industry. ]

Re:This just in!

He said "real severe clinical depression". That's the 1/3 you're talking about where the drugs work. Many people are diagnosed with depression based on just the most general definition (feeling "down" for longer than 2 weeks). And most people should only be treated with therapy. Today the drugs are handed out like candy. If they were only handed to the people that genuinely need them you'd find anti-depressants work quite well, which seems to be what TFA is saying.

Re:This just in!

As its been widely noted this study does not take into consideration as a variable those patients that talked about their depression with a psych or councilor and those that didn't.

Anti-dep medication allows you to handle your current situation enough so that you can go and talk to someone about your wider issues.

Its a band aid. The real fix is to find the thing making you depressed and fix that. And you need to talk to someone for that.

Re:This just in!

I have to agree. My sister and mother are both are anti-depression meds... And I used to feel I was depressed, but wouldn't do anything about it.

I no longer feel depressed and I know why: I have hobbies now.

My mother and sister don't have hobbies at all... They just sit around and play games or watch tv... They have nothing to look forward to each day, or even each week.

Me, I can't -wait- to get home and mess with one or more of my hobbies at any given time... I've got so many that it's actually a burden at times to decide what I want to mess with... And I want to add more.

It really was the difference between wondering what life's about and loving my life.

I'm not a doctor, and this isn't the solution for everyone... But I'd bet a -lot- of people would be better off if they had things to look forward to, instead of living life minute-by-minute and never looking forward. Having friends is not 'having a life'. Having a future is, and that -should- include friends to do those things with.

Re:This just in!

I actually think this is a wonderful advice. Doing these things makes you forget how shitty your life is and when you actually get at them, your life isn't shitty anymore. The worst thing to do is to just lie around and sulk. You become focused on your own depression and that just makes it spiral out of control. Well, sometimes that actually IS the only thing I want to do when feeling down - and in that way it is maybe not so hard to understand how depression happens to people.

Sometimes just cleaning my room, or doing the laundry helps me get up again. And having a fairly regular life, eating good food, and getting outside, if not only to walk around a bit. Heck, even writing comments on slashdots can help.

The basic tenet of this philosophy is to "keep yourself busy". Don't ever just sit down and let the feelings overwhelm you. By and by, they diminish and life won't suck anymore. I know this isn't enough for many people and I suspect a lot of "you have no idea what _I_ have been through". But I think people should TRY. We are often too quick to judge something as clinical depression and sometimes forget that depression is also a normal state of things that CAN be overcome by effort. Even when it gets so bad that you don't leave your bed for a week - it CAN be normal - or at least inside some manageable neighboorhood of normal.

As for the last thing: Stop feeling sorry for yourselves! This might sound harsh, but feeling sorry for yourself is the worst thing you can do to yourself.

Re:Depression not natural?

I think you're confusing depression as in "Man, I'm pissed off today" and depression as in the medical condition. "Real" depression is a horrible thing and needs treatment. It's as if you're saying cancer neends no treatment, since the cells grow very naturally.

Re:Prozac changed my life

Prozac == fluoxetine, which is mentioned in the article.