Do Antidepressants Actually Work? Research Says Probably Not

British researchers have released a report that claims that antidepressants, for the most part, are ineffective.

The researchers found that compared with placebo, these new-generation antidepressant medications did not yield clinically significant improvements in depression in patients who initially had moderate or even very severe depression. The study found that significant benefits occurred only in the most severely depressed patients.

Keep reading

So what makes this study different?

There are plenty of studies about antidepressants. What makes this one so important -- the results were front-page news across the U.K. on Tuesday -- is that the researchers were able to track down comprehensive unpublished trial results from the drug makers themselves before the drugs were authorized for sale in the U.S., and include them in their review of the literature. The U.S. Food and Drug Administration (FDA) must receive records of all relevant pharmaceutical-company trials, both published and unpublished, before it will approve a drug. Under the Freedom of Information Act, the researchers writing in PLoS Medicine were recently able to obtain those FDA records of industry-sponsored clinical trials. They yield data, they believe, that lets them avoid a bias that often plagues reviews of previous research: the tendency for conclusive positive results to be published, sometimes more than once, and thus over-represented, while mediocre results can be ignored or even swept under the rug.

Keep reading the Time article.

Find out which treatments do work.

Read more about Prozac's inefficacy here.

Find out how researchers came to these conclusions.

Read blogger Dr. Belisa Vranich's recent column about sex and antidepressants.

Do you or have you ever taken antidepressants? What's been your experience with them? Tell us below in comments.

Comments

[LHelm]

"The number to treat" with most antidepressants is 2. "The number to treat" with many cardiac drugs is around 50. (This term is used to describe the efficacy of a drug. The lower the number the fewer patients need to be treated to see a clinical results.) The FDA only determines if a drug is better than placebo in the aggregate.
Before trashing the psych meds - which definitely have side effects (clearly more than placebo) one might want to consider that most depressions have a natural history, where they would ultimately resolve on their own. That doesn't mean that the meds don't work.
As the article pointed out, they do work in severe cases.
The most severe cases of depression are life threatening.

[czarlos]

I have gotten through two depressive spells of varying intensity with the help of antidepressants, the longest one lasting over a year. What may have been different in my case, was that I took the herbal antidepressant St. John's Wort (containing the active ingredient Hypericum) instead of a prescription antidepressant. While the pills were not a "cure all" (and for depression, no drugs should be expected to be), they made a noticeable impact on my symptoms, which helped me get through the day and allowed me to think straight enough that I responded better to things like therapy. St. John's Wort also has fewer side effects than prescription meds. (NOTE: having tried various brands of St. John's Wort, I have found the brand sold nationally at Trader Joe's to be inexpensive while containing the claimed amount of Hypericum, which can be an issue since herbal remedies are not regulated by any government department of oversight in the US).

[dguller]

Just a few comments on the meta-analysis:

First, the NEJM review showed that most antidepressants DID work (i.e. were statistically significant over placebo), but that their effect sizes were exaggerated to varying degrees depending on the drug in question. The average effect size was still 0.31, and for some medications was even higher (e.g. Effexor 0.40, Paxil 0.41). Furthermore, the FDA studies for Celexa, Paxil and Effexor had NO negative trials at all, and Prozac only had one negative trial that had 42 people compared to the positive trials that had 1,100 people. So, it appears that these medications, according to that more comprehensive review, ARE effective.

Second, this new study only includes the FDA studies performed BEFORE the drugs were FDA-approved, and thus do NOT include the dozens and dozens of newer trials that have shown efficacy. The pre-approval studies are typically skewed towards showing ANY efficacy without side effects in order to get approved, and then better studies are performed to clarify dose ranges and duration of treatment. The authors of this study ignored all subsequent trials, because they felt that they would be biased, because they were sponsored by the drug industry and their negative results could be quietly hidden away. Although this is a legitimate concern, it seems equally suspicious to categorically dismiss an entire set of data without examining it.

Third, the FDA studies typically lasted only 4-6 weeks, and prospective longitudinal studies carried out afterwards showed that most antidepressant efficacy occurs after this time period, and so it is unsurprising that there was a small statistical difference between placebo and medications. Furthermore, other studies have shown that relapse rates are significantly higher in follow-up for those who were taking placebo compared to those on antidepressants.

Fourth, it did not even include all SSRI's, including Citalopram, Escitalopram, and Sertraline. Thus, it's data is incomplete. Also, Effexir is NOT an SSRI, but an SNRI.

Fifth, there is a significant placebo effect, typically 30-40% efficacy, in MOST drug studies, largely because people who are enrolled in such studies get a great deal of attention from physicians, nurses, pharmacologists, social workers, and anyone else involved in the study. The question is what happens once this attention is removed, and studies have shown that the placebo effect typically wares off whereas the pharmacological effects remain to a large degree.

Sixth, the FDA studies excluded individuals who were SUICIDAL. That makes generalizability difficult in any case, but the studies are clearly limited due to the fact that they excluded a priori those MOST in need of these medications.

All in all, an unimpressive study by authors whose past work clearly biases them against medications whose conclusions are not entirely novel. For minor depression, medications are unnecessary; for moderate depression, medications or psychotherapy are helpful; and for severe depression, medications and psychotherapy are needed.

A final thought, the efficacy of psychotherapy is often compared to medications. CBT, for example, has been found to be equally effective as medications, especially for moderate depression. So, if medications don't work at all, then psychotherapy doesn't either, which leaves us with what? Exercise?!

Wonderful.

[shinybear]

I think there is a healthy middle ground between Tom Cruise and willy nilly mass medication.

Many of us are justly concerned about over prescribed drugs and their side effects- especially their withdrawls which in children have been proven to cause suicidal and even violent behavior.

Yes chronically depressed people need their meds.

But what about talk therapy? HMO's would rather put you a lifetime of drugs then spend for the time consuming and expensive but ultimately needed talk therapy.

[nolalily]

I agree with you. You sound like you know what you're talking about.

[Kungfublood]

Antidepressants have certainly made the drug makers and their pill pushing quack doctors very happy.. and isn't that what America is all about today?

[Dots]

I, too, have received enormous help from anti depressants over the years...bu­t the effectiveness always wore off/symptoms returned and I had to switch. (Paxil, Prozac, Cymbalta) Now, at 72, I'm not taking any...and I'm doing well...may­be my body chemistry has changed.

[auramac]

Whatever gets you through the night.

[wheelskeepturning]

All I can tell you is that Prozac worked for me. I had a problem all my life with anxiety. I had no idea there could be a cure however something happened and the doctor wanted me to try Prozac. To my amazement after 4 months I noticed that my anxiety in new situations, meeting people, work situations, completely disappeared. Something that had caused me so much apprehension was now gone and has not reappeared in 10 years. I was cured. The thing that initiated me taking it in the first place was a temporary situation. I decided to quit taking the medication to see what would happen. AT first I experienced what I call "brain buzz" I noticed a little "zzzzz" every once in a while and then it was gone. I am so happy that I got to take Prozac. I think the problem is that people think they have to be on it for ever. It cured me in 4 months and I was taking it for a completely different reason. I never feel apprehensive in new situations now. I just go right in and take whatever comes.

[dora rice]

good...

[wadenelson1]

Anyone who has ever been HELPED out of a serious depression by anti-depressant medication KNOWS the conclusion(s) reached by the author of this study simply are not correct.

[Dvmx]

Absolutely true, This report is unfortunate, because people who have a grave case of depression might not seek the help. If you have watched a friend in severe depression, huddled on the floor in the corner in tears, unable to get up, let alone go out, and seen them rally and return to near-normal in a matter of days with Prozac, you know it's not the same as a placebo.

Basically, if you can get the same curative effect from a placebo, you were not severely depressed.

What's more, with the floor that Prozac (or similar drugs) establishes to prevent the dark-hole free-fall, it seems the patient can learn alot about depression while under treatment, and can eventually ease off and do without it.

[hontonoshijin]

Suffered depression all my life. So did my father, back when nobody did a damn thing about it. So did his father, as near as I can tell.

Smoked maryjane as a youth because it helped me transcend briefly. But in my opinion it backfired. In my fifties began taking first effexor and then an ssri whose name I can't remember. Seemed to help. Then a number of things went wrong, and while still taking the ssri went through the scariest and most ghastly depression I ever had. Plus constant nausea. Plus as mentioned, lower libido. Lower libido depresses me. Rightly or wrongly, I concluded that the pills were counterproductive and quit them. Have not had any for more than four years. Had always exercised, and was familiar with the antidepressive effect in me long before it became clinically well-known. Also exposure to sunlight. Also working in the dirt.

Began yoga about the same time I quit the pills. Still have the pull to depression, but for me hatha and prana yoga, exercise, sun, gardening or landscaping, a careful diet based on my observations of cause and effect in my own being, and general if not total abstinence from alcohol and other psychoactive substances (also based on observation, because I LIKE them) keep me on a pretty even keel.

Do not say any of these things to condemn any behavior, just to add a bit of anecdote that may be helpful to some.

[jhamm1]

I can relate. As one diagnosed with type-2 bipolar and OCD, I intiated anti-depressants when I was a freshman in high school, at which point I found it progressively difficult to concentrate, and the symptoms of my depression appeared to excacerbate themselves. Under the impression that my disease had gotten worse, rather than face the prospect that the medication might actually have been compounding the problem, I proceeded, and as a result became further distanced by some of my friends, who by now had inquired to some of my family members behind my back as to why I was acting "so strange". Eventually, I was forced to drop out of college, and only upon rejecting the medication altogether, did I finally manage to resume schooling and obtain my degree. Admittedly, symptoms of my illness continue to manifest themselves, but hardly arrive in such an unmanagable fashion as those that transpired when I was on anti-depre­ssant.s

[hontonoshijin]

Cannot refrain from further comment. Depression, as someone in the comments section noted, is terribly painful. It is comparable to, but worse, than being gnawed to death from the inside by larvae. So can hardly blame anyone for trying to escape it by any means possible, short of harming others.

What follows is speculation. Based on personal observation, but speculation nonetheless.

It struck me a long time ago that depression involved a nasty feedback cycle, amplifying its own destructiveness. Feedback cycles are very very hard to break. Have gradually learned to simply refuse to follow out lines of thought which I know from experience lead to despair and nothing else. But developing the ability to refuse these habits of thought is a long process, and requires a great deal of effort and attention.

I wonder if this is not why I have found yoga so helpful: Yoga trains the being, not the intellect, to master states of mind (as well as states of the body--and fear, usually a powerful component of depression, is a BODILY state). Yoga requires regular practice over a long period of time. It is a matter of retraining perception and habits. It is impossible to think your way out of depression. Mere intellectual recognition does not avail. I recognized the dangerous habits of thought a long time before I learned to control them. New habits are required, and they may be built only slowly, with practice.

Too bad, but it's a lot better than despair

Will add this: Depression is not, in my opinion, caused by outside conditions. One may function as well as possible though the world is a mess. The most useful response to the pain and trouble of life is not internal pain and trouble, but honest recognition of the situation coupled with equanimity.

[Libby29]

If I were diabetic, I would take insulin. I have a chemical imbalance which causes the constant reuptake of serotonin(it never gets to where it needs to go), so I take selective serotonin reuptake inhibitors to keep that from happening. Exercise has the same effect, at a much smaller level. In order to achieve the same effect as an SSRI, one would need to quit their jobs to exercise enough. And just like insulin saves diabetics, paxil saved my life. Without it, I am suicidal, cannot function for thoughts of loved ones dying, suffer from extreme agoraphobia which I have had since birth, OCD that gets in the way of living, and panic attacks galore. My condition is not mental, and cannot be solved through counseling. I really have not had any bad situations in life, so nothing has caused my constant depression, fear and anxiety except a chemical imbalance. Without paxil(I tried many, it works for me), I function very poorly. Just like if someone suffering from diabetes, hyper/hypo­thyroidism­, pituitary problems did not take their medication. It is very real, and many individuals would be saved if researchers and critics would quit trying to prove that it isn't.

[RobinLandseadel]

I have little doubt that the drugs work for you. The real issue is how lazy the Psychs are, doling out such potentially hazardous chemicals to folks who have problems that require address by means other than one of these wonder drugs. Doubtless many have been saved by Lithium as well. The real issue here is over-prescription of drugs that have rather specific uses, applying the drug to situations that clearly require actual personal interaction between doctor and patient. But the world's load of crazy people increases as our collective shit approaches the fan. Folks who get [increasingly] depressed have damn good reasons to be depressed. That doesn't require a pill, that requires a makeover of the world.

[Phaedrusnyc]

I wouldn't be so quick to blame "lazy" psychs. The vast majority of psychiatrists and psychologists I know of recognize the efficacy of the talking cure and other methods when dealing with depression. If the HMO's and insurance companies actually PAID for these things, they could be used successfully in conjunction with medication, which IS effective on the micro scale, even if a meta-review sees that it isn't on the macro-scale. unfortunately, those people lucky enough to have insurance are rarely lucky enough to have insurance which pays for the full range of psychiatric treatment. Drugs are cheaper, so drugs are what we get.

[Clem2]

I don't know if they work or not, tho I suspect they do work. I was on Zoloft for a time and definitely it helped me sleep, which was my main problem. After 25 years of trying anything and everything, this was great.

However, then I developed arthralgia (took me a while to realize the Zoloft caused this and at the time my Dr. said this was impossible). But found someone else on the internet who said she, too, had the same problems!

It took over a year for the pain to go away. I tried Zoloft again, several times, and now only a small amount of it caused the pain to come back much more quickly.

So... gave it up.

I've never been able to handle the side effects of any other antidepressant, either.

OTOH, I do have friends who say these drugs really have made a huge difference.

I don't know... I'm not very suggestible, which is maybe why they have not worked for me. But the Zoloft did something that was good.... until I got the side effects which were debilitating and certainly NOT imagined.

I wonder if the article notes that about l/3 of those who try AD's cannot take them due to side effects.

[amanda85]

I don't know if antidepressants actually work or not, or maybe partially work. I'm not a doctor or even a student of medicine.
What I know is that antidepressants are excessively prescribed in America, by doctors who are totally in the pockets of big pharma, and the results are nothing short of disastrous. Prozac and similar drugs are prescribed to SMALL CHILDREN on a regular basis for extremely mild cases (IF there is a case at all...), when good ol' "sun therapy" (i.e. take your kids out instead of letting them spend all their free time watching tv or playing computer games...) would work just as well.

[middleofnowhere]

actually, I work with adults and children with severe psychiatric disorders. I guess until you're faced with a young child who is actively homicidal.­.. well, you may not get it. sunshine is helpful (as is any light therapy) in mild depression. many anti-psychotics are prescribed for very real problems; sometimes those problems come packaged in a very sweet-looking five year old; who likes to kill animals, set fires, molest other children, suffers from hallucinations and delusions.­..

oh, yeah... you're right! don't medicate any of these problems. just let the poor child go on; become an adult, not learn any coping skills, stay off of any helpful medication, and... well, end up in prison, as adults. yes, I work with the severe of the severe. but I do agree that mild cases should have alternative treatments for children and adults. it's just that not many people receiving medication for psychiatric disorders are mild cases.

oh, and of course I find it irresponsible for people to be obtaining psychiatric medications from their MDs. there definitely should be a definitive diagnosis made by a psychiatrist or LCMSW, and therapy should be in conjunction with medication.

[johntal]

Tom Cruise financed this research for sure. Scientology works far far better than any pill

[MrsWakely]

people who have suffered, as I did for 20 years, from depression, anxiety, panic and ocd, and then found relief they never thought possible through the right ssri, don't really care about this kind of a post, or those who "agree" with it. I tried everything: cognitive behavioral therapy, talk therapy, I've always exercised, ate fine. everything. I never imagined an ssri could work. they do. they saved my life. literally. yes, they need to be closely, and I mean closely monitored in children, AND adults, yes, you need to taper off ONLY with a doctor's oversight, if you try to go off, yes, you gain weight, yes, you lose some/a lot of your libido, all of these things have made me very upset at times over the five plus years I've been on paxil. and you should ONLY be prescribed by a GOOD psychiatrist, with a lot of experience with the various drugs, NOT ANY OTHER TYPE OF DOCTOR - they simply don't know enough about mental health or the various medications, but, the alternative? I read once where a woman had suffered from depression as well as battled cancer, and she said depression was much worse. I undestand. when you are clinically depressed, you, on some level, wish you could just not be in so much pain. that's all. It's excruciating. ONLY people who have experienced that hell understand that YES THERE IS something to chemical imbalance, and these are life saving medications. everyone, and I mean EVERYONE else? should shut the fuck up.

[Nutcase]

You are entitled to have your opinion and base it on whatever misinformation you have been gullible enough to swallow. You are not entitled to tell me not to express my opinion.

I suffer from manic-depression. I lost my first wife who had depression. My eldest surviving son has depression. I have endured suicidal ideation for months at a time. I have served as a full-time advocate and lobbyist for those with mental illness (you included). I served as a field director for the National Institute for Mental Health. I have worked as a neuro-researcher. Your 20 years is far less than half the time I have experienced mental illness. You are not the only person afflicted with mental illness entitled to express an opinion.

[eddiestardust]

Nutcase,

Why choose "Nutcase"? Why would you belittle yourself buddy?

Look, as a past member of NAMI, member of the congressionally mandated hospital monitoring project and general advocate of those mentally infirmed, I have seen folks benefit greatly.

I'm sorry that you have not.

And my youngest brother lies 6 feet under because of all those who helped him to refuse
medication!

Seeing him suffer, and seeing some of the results of the medications, I know that he could have found a balance if only he had decided NOT TO REFUSE TREATMENT!

Maybe one of the better known American citizens who has struggled and won her fight with Manic Depression is ...

PATTY DUKE

Why don't you google her story???

[sawdustinhershoes]

Well, gosh, I guess you've named yourself aptly. Now it's a contest to see who's the most mentally ill?

I don't give a rat's ass what your and your family's experience has been, it's irresponsible to denigrate drugs that have helped millions of people over the years.

I'll guarantee you that I wouldn't be here if it weren't for antidepressant drugs. In fact, I know five other people who wouldn't be here either. We've all remarked this point to each other over the years.

I ended up in the hospital with depression when I was 30. It was the first time someone was able to tell me what was wrong with me. I am bipolar. That was 21 years ago and I have been on antidepressants since then. I still have depressive episodes but they are much less severe and shorter.

My friends were contemplating suicide, one was even planning to take her 3 yr old son with her, because she felt no one else could take care of him after she was gone. The antidepressants saved all our lives - and the life of that little boy.

What people don't understand is how insidious depression and mental illness are, and how it's so easy for someone to succumb to the pain of depression and kill themselves.

I'd imagine MILLIONS of peoples lives have been saved by antidepressants and many more millions have had better lives due to these drugs.

I for one, KNOW I can't live without them, believe me I tried.

The issue with doctors overprescribing these drugs is separate and should be addressed. But in the meantime, erroneous reports such as those cited in this "study" are irresponsible and will result in people dying because the best avenue for them, the drugs, are being attacked by people for whatever reason.

When someone like me has a biochemical imbalance that can be treated, just like someone with diabetes, or thyroid problems, then it is criminal to try to withhold these drugs due to some misguided judgements usually made by people who know nothing about what they're saying.

Biochemical imbalances generally don't fix themselves, and all the sunlight and proper diet and exercise doesn't fix it either. I know, I've tried for 21 years. The pills, however, do work and they make me far more able to interact with my family and friends on a sane productive basis.

My life is livable because of the medicine.

[sawdustinhershoes]

Well, gosh, I guess you've named yourself aptly. Now it's a contest to see who's the most mentally ill?

I don't give a rat's ass what your and your family's experience has been, it's irresponsible to denigrate drugs that have helped millions of people over the years.

I'll guarantee you that I wouldn't be here if it weren't for antidepressant drugs. In fact, I know five other people who wouldn't be here either. We've all remarked this point to each other over the years.

I ended up in the hospital with depression when I was 30. It was the first time someone was able to tell me what was wrong with me. I am bipolar. That was 21 years ago and I have been on antidepressants since then. I still have depressive episodes but they are much less severe and shorter.

My friends were contemplating suicide, one was even planning to take her 3 yr old son with her, because she felt no one else could take care of him after she was gone. The antidepressants saved all our lives - and the life of that little boy.

What people don't understand is how insidious depression and mental illness are, and how it's so easy for someone to succumb to the pain of depression and kill themselves.

I'd imagine MILLIONS of peoples lives have been saved by antidepressants and many more millions have had better lives due to these drugs.

I for one, KNOW I can't live without them, believe me I tried.

The issue with doctors overprescribing these drugs is separate and should be addressed. But in the meantime, erroneous reports such as those cited in this "study" are irresponsible and will result in people dying because the best avenue for them, the drugs, are being attacked by people for whatever reason.

When someone like me has a biochemical imbalance that can be treated, just like someone with diabetes, or thyroid problems, then it is criminal to try to withhold these drugs due to some misguided judgements usually made by people who know nothing about what they're saying.

Biochemical imbalances generally don't fix themselves, and all the sunlight and proper diet and exercise doesn't fix it either. I know, I've tried for 21 years. The pills, however, do work and they make me far more able to interact with my family and friends on a sane productive basis.

My life is livable because of the medicine.