Beyond Blue

Beyond Blue

The Latest on Antidepressants: Be Careful Where You Get Your Facts

James Gordon, author of “Unstuck” and Charles Barber, author of “Comfortably Numb” present some interesting statistics on antidepressants. However, for persons like myself who suffer from severe depression, some context is needed to their facts. An article in the Summer 2008 issue of “Johns Hopkins Depression and Anxiety Bulletin” fills in the blanks that leave people thinking that antidepressants aren’t effective at all. Excerpted from the article, “Report Card on Antidepressants” by J. Raymond DePaulo, Jr., M.D., are these paragraphs:


A study released last week reported that depressed patients put on antidepressants get better at only a slightly higher rate than those treated with a placebo, which is essentially a sugar pill. This is, of course, a potentially concerning finding for people like me, who prescribe antidepressants, and for those of you who take them.

The results, reported in the open-access journal “PLoS Medicine,” come from a combined analysis of 35 studies with more than 5,000 patients, evaluating four of the newer antidepressants–fluoxetine (Prozac), venlafaxine (Effexor), nefazodone (Serzone), and paroxetine (Paxil).

The new twist is that this report includes data from many studies that were conducted by the drug companies and filed with the U.S. Food and Drug Administration but never published in academic journals.


What the PLoS study found is that, on average, patients taking medication had a substantial response as measured by a depression rating scale. Whereas they started with a score of roughly 26 (on a 54-point scale, where higher means more depressed), they dropped after six weeks of treatment to about 16.

But the patients taking placebos also, on average, had a strong response, dropping to about 18.

However, the placebo picture was a bit more complicated. Unlike the antidepressants response, which did not vary based on how initially depressed patients were, the placebo response was strongest in the LEASED-DEPRESSED folks, dropping off in those who illness was more severe.


So here’s take-home message No. 1: Antidepressants showed a significant advantage over placebo for the severely depressed patients but not for the mildly and moderately depressed patients.

Maybe that’s not really so surprising.

It is well established that mild and moderate depression can respond to psychotherapy alone, without medication. For example, Dr. Michael Thase, a psychiatrist at the Western Psychiatric Institute, and his colleagues found in a 1997 study that the advantage of antidepressants added to psychotherapy only came when depression was more severe.


It is not unusual for a depressed patient of mine to come into my office sad and weepy, and leave after an hour feeling buoyed up. There is a sense of relief that comes from being with someone who understands and a sense of hope that comes from being with someone you feel has the power to make things better.

These are important aspects of what happens in psychotherapy, and they are likely important aspects of the placebo effect. Patients who receive placebos are being seen by medical staff and are getting some of that relief and some of that hope.

Sometimes people fail to realize that what medication does and what psychological factors do both have an impact on the brain. Dr. Helen Mayberg, now at Emory University, studies brain circuits in depression. She used a neuroimaging method to study metabolism across brain regions in patients who responded to Prozac and in those who responded to a placebo.


She found that, among the placebo responders, there were a number of specific regions with metabolic increases and others with metabolic decreases. These same changes were also seen in the Prozac responders, suggesting that this is what the brain needs to do to feel better, regardless of how it gests there.

But that’s not the whole story. Because there were also some changes unique to the Prozac responder brains, Mayberg and her colleagues speculate that these other changes might be important in maintaining longer-term response and preventing depression.

Indeed, to return to the PLoS study with which we started: It would be interesting to know what happened after the six weeks that most of the individual treatment studies lasted. Were the patients who responded to antidepressants more likely to stay well longer than those with a placebo response?


A recent study by Dr. Arif Khan and colleagues at the Northwest Clinical Research in Bellevue, WA, addresses exactly this question. They analyzed antidepressants studies in which drug and placebo were continued in responders for at least four months. The result: Placebo responders were more likely to suffer a recurrence of depression than antidepressant responders.

And now for take-home message No. 2: There still might be some advantage to antidepressants even for mild and moderate depression.

To read more Beyond Blue, go to, and to get to Group Beyond Blue, a support group at Beliefnet Community, click here.

  • Wendi

    I’ve reached a point where I don’t care anymore what “experts” or studies say about anything, especially in regard to mental illness. Every brain is different, and there is no magic solution for everyone. So I’m the expert on my brain chemistry now. And here’s what I know: Prozac saved my life. Period. Without it I wouldn’t be here. Period. I don’t need to know anything more than that. 😉

  • Sally T.

    I’m with Wendi.

  • Melzoom

    I probably fall in the severe depression category, but I also agree with Wendi. When Zoloft stopped working and my doctors didn’t realize it, they kept upping my dosage. My depression got worse–ending with the “I hope the ocean would help you see” story Therese posted. If it had just been a placebo-effect, why did the depression get worse when they increased my dosage?
    My current med (Effexor) is really working for me. And that is all I truly care about.

  • Kathleen

    I’d like to say that while I firmly believe that antidepressants helped me considerably after I developed severe postpartum depression, there were also some very significant side effects of ….. manic behavior (sometimes subtle, sometimes not so subtle) that ruined my relationship with my husband and led me down a path of one bad mistake after another and then years of stress trying to fix those bad mistakes. It’s very important to have someone in your life who knows YOU and can articulate to you in a way that makes you understand when irrational behavior sets in. I caution all of you on antidepressants to watch out for this.

  • Patty

    I agree with the both of you. I have had seven deaths in my family in a years time and only feel mildly depressed. I rely on God to be my medication, he is all the strength I need. And speaking of God, that’s what doctors aren’t! They can only guess/think what we need. The one who knows what we need is God and us. We (the patients) know what works for us….and at what strength/dosage.
    Thanks, and God bless,
    You’re in my prayers sisters and brothers.

  • Larry Parker

    Given that I’ve been battling the anti-medication crowd on my own Bnet blog lately, it’s good to have some cavalry as reinforcements …

  • Larry Parker

    And, on the ongoing New York Times Well blog on bipolar, I am just floored how many people writing in are actively anti-medication (http://)

  • Barbara formerly Babs

    I believe that anti-depressants have a place in the treatment of mood disorders. I have been on and off them for probably ten years. I do better when on them.
    I, too, question the length of the study. I also wonder how the expectations of the persons taking the medication can be evaluated? That would also figure into the length of the study. Do people expect rainbows and sunshine; that their troubles will melt away? Do the placebo people fall back into depression when the initial response wears off/ Do those on medication do better in that case?
    Finally, I believe that God plays a significant role in *any* healing that takes place in us. I also think that the use of medications does not show a lack of faith the healing power of God, any more than seeing a doctor for the repair of a broken bone does.

  • clarie

    it’s really, really important to see the best doctor, psych, not just medical doctor, and get the right diagnosis of depression or bi-polar. before using anti-depressants, because they only do a little if you’re bi-polar or worse.
    in my exp. doing anything it takes to get you out of your quicksand, or mania is what works. you know how a stocking runs, or when you’re knitting you drop a stitch? well, that’s what happens. it may be one dropped stitch – a bad job – but it can pull the rest of your treatment down with it. then the meds don’t work like they’re suppose to. maybe that’s why these conflicting studies are so hard to understand.
    stitches can be picked up in treatment and a piece of knitting, it’s just a lot of careful work

  • Larry Parker

    One of the anti-medication bloggers attacking me on this issue said any mental health consumer who does not agree with James Gordon is a “chronically ill, disabled drug addict.”
    Good to hear she’s non-judgmental …

  • Anonymous

    In my opinion, this is more a support for the already proven fact that pACEBOS HELP SOME PATIENTS THAN IT IS AN INDICTMENT OF ANTIDEPRESSANTS. It has ong been know that some people are responsive to placebos for WHATEVER medication they are using and regardless of the illness being treatd, including cancer.I find it interesting that there is no mention of a control group who took neither; doesn’t that skew the results a bit? I know that in my case, my sisters have ALWAYS been able to ascertain through observation when I used to stop taking my antidepressant because of the stigmas attached and the “pull yourself up by your bootstraps” mentality on which we were all raised. Within days, one of them would question my faithfullness to my medication; it was THAT obvious. I think the title of this post says it all, folks. Anyone who has ever taken a statistics class knows that there are erroneous conclusions drawn from nearly EVERY study,which also proves the importance of a highly analyzed control group. when al of the data is disaggregated.

  • Nancy

    Larry…with my heart I hear you and appreciate the fight you are fighting. I do not wish to support the people who are so rabidly anti-med
    …CoReg, a heart med, saved my life as far as I can see. Byetta, a diabetes med, has given me some clarity. My experience with antidepressants was not so grreat. I was fine on 25mg of Zoloft…on 50
    I wanted to gouge my eyes out. It was absolutely bizarre. I was switched to Paxil…it seemed to work great. I have hypertension, since my teens, that responds poorly to meds. On the Paxil I decided that the reason my blood pressure was so bad wwas because I held too much inside…so I proceeded to tell everyone what I thought…unfortunately, in my disinhibition, I wasn’t particularly careful how I told them. Like Kathleen, ten years later, I’m still trying to pick up the pieces. I managed to destroy my relationship with three of my four children.
    I don’t see anyone talking about the Cytochrome P-450 relationship to the metabolism of anti-depressants. People are, INDEED, different in the way they respond to meds…there are genetic reasons for that.
    Because of an interest I’ve had in serotonin, and the reading I’ve done for over two decades, I have been very interested in the SSRI’s. I think a big part of the problem here is the complexity of the human brain. As researchers and doctors try to learn more to help people, they often don’t know all the consequences of the treatments they develop until they are used by a large number of people. Some people have suffered severe negative reactions to antidepressants.
    I don’t think the problem is that antidepressants are bad…I think it’s that not enough is known yet about how they work in different people with genetic variations.

  • Tracey

    I have been taking a drug called Zoloft for some three years. I am definately better on them rather than off. but have now reached the highest does allowed, and plateued. so the next level, if i was to change, which i have to do. zonk me out, i am unalbe to function normally. I wake up with that thick head, like you have had 500 drinks and i dont drink!
    So i dont know what to do really. The placebo effect is certainly something to think about, it clearly states on the packet of zolofot do not stop, you have to wean yourself off. well i’m not so sure, there have been times that i have gone away and not taken them for a week, or times at home when i just forget. nothing happens, i’m still here. still full of grief, but no different. i’m thinking a good councellor, you know, like you see on tv. you lie on the coach we talk. you heopefully get better. but i cant seem to find one. I think personal refferal is the key to that one. but because i am so depressed and full of grief, i dont have any friends to give advise on who to use, catch 22 situation. if you know anyone,i live in seven hills, sydney nsw. i’d love to hear from you,

  • Sandy

    The use of SSRIs like Zoloft and many other meds come with many cautions. The caution of stopping the med without gradually weaning can cause some significant side effects. The fact that you did not experience them may be just luck or the half life of the drug itself which tends to self taper due to a longer half life of the medication. Also with many of these medications your body can build up a tolerance to them and they will become less effective with chronic use. Switching to another type of antidepressant as opposed to an increasing dosage of a simlar SSRI may be of some help. Unfortunately, for many of these drugs, it will take up to 4-6 weeks to feel the difference. This should however be discussed with your healthcare provider and alternative medications discussed along with the risks and benefits.
    For those who are significantly depressed couseling is a must. Finding a good counselor is always difficult as the belief systems and personalities often get in the way. Just keep trying and never just give in to the depression. There are always those of us here who are willing to listen when you need to talk about what is going on in your situation.

  • Desiree

    I have been taking welbutrin for awhile now, and it has really helped. But, I have finally started to realize is that part of my depression, comes from not letting go of past hurts, or anger at myself as well as others, and even toward God. I’ve begun to forgive myself for not being perfect, and to let anger towards others go, although that does not mean opening up old relationships that have been destructive and hurtful, just letting go of the past and learning to forgive a little better. I’m grateful for the medicine. With it that dark heavy feeling lifts, and I stop starting to cry in the line at the grocery store. I’m also learning that the reason I’m crying in the grocery store was the day my husband and I learned of his brain cancer, so maybe I just need to lighten up on myself, and realize that’s normal. Even so, I’m grateful for the medication. There are those out there who are so hostile towards anti-depressants. I guess they have their reasons, but they have sure helped me. It reminds me of the story of the man on the beach throwing the starfish that had washed up on the beach back into the water. Someone comes along and says, there are thousands of these star fish on the beach how can you probably make a difference. As the man threw another one back in he says “well it matters to that one.” Or so the story is told.
    Also, I know that welbutrin is not what really helps me, I know that God helps me. And I always know that

  • blanche

    All I know is that I was switched from 200 mg Zoloft to 10mg Lexipro, and what a difference. Everyone is individual, and whether or not you take medication, best of luck to all of you. God Bless.

  • Jeffrey Wilson

    I took numerous different antidepressants for 23 years with various results. But I did not get my life back and function like a normal human being until I figured out the cause of my depression and got off the drugs once and for all. The drugs clouded who I was and caused me to walk around in a pharmacutical coma for 23 years. Check out for the real story.

  • Brian

    I agree with antidepressants being better for the severely depressed and to prevent remissions. The anti antidepressant crusade seems to be made up of people who either have never been depressed, only mildly depressed, or had depression of an exogenous nature (psychological).
    It’s hard to “get it” if you haven’t stepped in someone else’s shoes.

  • Fuzzlizard

    You use the term “LEASED-DEPRESSED”. Did you mean LEAST-DEPRESSED?
    Dang…if it is Leased Depressed…can someone give me directions to the dealership? I want to trade this lemon in for a new one. :) Maybe a HAPPINESS with financing — 3.29% APR for 30 months?

  • Nancy

    I agree with Blanch that Lexapro is a God sent.
    After trying so many “cocktail” combinations and having my sister-in-law (who is a nurse and seem her husband and their kids use Lexapro) finally said force your doctor to put you on Lexapro (and having a doc try to get me to do another “cocktail” until I said either do it no or I walk)and to feel and see the immediately change….nothing compares.
    It’s hard enough being depressed and suffering anxiety but to find out that a lot of the issues I was mentally suffering had to do with having lower then normal serotin levels…once that increased the other issues triggering the depression was able to be dealt with by counseling.
    Nancy aka sixlittlekitties

  • Melissa

    I’ve been taking Zoloft for a little while with not much improvement. I’ve read on this websight about Lexapro and how it seems to give better results. I’m going to have to refill soon so I’ll ask my doctor to write a script for that instead. Hope it helps cause I’m just not having much relief, I wish they could guarantee one pill that will absolutely, positively, quickly, without any side effects, like eating yourself sick, to work and perform miracles. I’m desperate to find at least something that will work. Tired of not getting more positive and lasting results. Am afraid that I will continue to feel this overwelming sadness the rest of my life. Hope this next one does the job. Lexapro, here I come….. Bye for now.

  • Troy Centazzo

    Hi Therese and All.
    I enjoyed your review. I’m working with Dr. Gordon, the Expert you discuss, to help him educate the public about natural approaches to treating depression. We’re following in Oprah and Eckhart Tolle’s footsteps and have created a free four part online web series called “A Natural Approach to Treating Depression,” starting on November 18th. It includes four video classes plus a bunch of free downloads – all for free. I’ve attached the essentials below.
    Even if people are pro-antidepressant, they may find the info useful without having to buy the book. Plus, Gordon does NOT recommend that someone just go off meds; this program can be used as a complement to mainstream treatment. This is a completely non-commercial event.
    Free Online Learning Event: “A Natural Approach to Treating Depression”
    Lesson 1 – An Overview of Depression and How You Can Treat it Yourself with the Help of a Guide
    Premiere Date and Time: Tuesday, November 18th at 8:30 EST.
    Lesson 2 – Relaxation/Stress Management. Premiere Date and Time: Thursday, November 20th at 8:30 EST.
    Lesson 3 – Exercise and Movement Premiere Date and Time: Saturday, November 22nd at 6:30 EST.
    Lesson 4 – Other Useful Techniques and Advice for Participants Premiere Date and Time: Monday, November 24th at 8:30 EST
    Resources Provided: The “Unstuck Pack”
    Participants can go to the website and download the free Pack, which includes:
    ? The Unstuck Workbook & Journal to use with the course
    ? An audio relaxation exercise for an MP3 player
    ? A guide to relaxation and meditation to use with the exercise
    ? A follow-along video, which demonstrates a relaxation exercise
    ? An excerpt of “Unstuck: Your Guide to the Seven-Stage Journey Out of Depression”
    Sign up and additional information is at

  • Mary

    I used to feel the same way most of you do until I came upon this eye opening site / blog and absorbed all the information.

  • Jen

    Mary- you can be pretty sure that when you find ‘a site’ or ‘a doctor’ or ‘an authority’ who has all of the answers to anything that it should be taken with a huge grain of salt. It’s very easy to find one-sided information on anything, but it’s more helpful to look at those sites and do some research on the studies that they cite, the background behind the videos, etc. No one has all of the answers, and the people who claim to do the most damage. A good background in basic science, the whys and wherefores of peer reviewed studies (and the politics involved), and a respect for something other than anecdotal ‘evidence’ will help you to make more informed decisions.
    Then again, it’s quite possibly your own site, so it could just be blogspam.

  • Meg

    hear hear Jen. A “MySpace” page? *Really*? More fear for the already fearful. What irresponsible dogma.

  • Bev M

    I know Oprah and Eckhard don’t know the first thing about DEPRESSION! And I wonder who this Gordon fellow is too. I’m not one who runs to the doctor for every minor ailment, but Prosac absolutely saved my life, and I’ve been on & off anti-depressants for 20 years. I prefer to stay off – but winter comes and I run the risk of falling into a lengthy depressive episode. I’ve been diagnosed (accurately it appears) with CHRONIC DEPRESSION – was a part of my life as a child, although who talked about depression in the 1950’s – especially in children!
    I was into the “new age” movement that Eckhard is in for many, many years – and not every problem is spiritual or able to be solved that way! Shame on Oprah for naively supporting such poo!
    After watching several friends (in recovery programs), it seems like many doctors are very willing to give almost anyone who presents with sadness or mild depression, a prescription for anti-depressants. Our culture and employers are not willing to let anyone “grieve” a real loss. (I knew a woman in 1992 who lost her husband suddenly and after 2 weeks of her being sad the bosses told her to “get something” to help her get through the day without wasting time crying!)
    It is not surprising to me that anti-depressants would not work very well (if at all) for persons who are not “clinically depressed” but just sad or going through a grief experience. Those people do not have chemical disorders!
    And, let me tell you from years of experience, do not ever listen to people who claim to have “THE ANSWER FOR EVERYTHING THAT AILS YOU” – they’re snake-oil salesmen no matter what they’re selling!
    God bless!

  • http://Http:// Asher Adelman

    Don’t let a Toxic Boss cause you to have Depression. Fight back at
    Nobody should have to work with a jerk.

  • bk

    I had to get antidepressants from the mail(ordered through the company) and in the summer it gets really hot. So for many months I suffered severely from anxiety, depression, and even some paranoyia from living with someone who wasn’t who I thought. It was the most horrific experience I have ever gone through. It was worse than a back surgery, and withdrawel from pain pills. It was horrific. The meds were toxic and I shiver thinking about what an awful experience this was. So never get meds in the mail. They have to be at a certain temperature to work. Please I don’t ever want anyone to experience this. Actually the medicine was Pristiq and it is the worst medicine I have ever taken in my life!

  • Your Name

    I am a therapsit at WPIC and enjoy your articles. they are helpful to
    my clients. Thank you

  • Mary

    I, too, have been on many anti-depressants over the years having been depressed even as a child. You name it, Paxil, Prozac, Effexor XR and too many of the older anti-depressant drugs to remember their names. The last time I went to my doctor’s office teary-eyed and sad as all get out, he talked to me about “recalcitrant depression”. In other words, you can be on an anti-depressant and begin to feel good again and a few short months later, you are back to the same state that you were before. It was discovered that in giving people with Bi-Polar Disorder a particular medication, their depression lifted greatly and stayed that way. So it was found that those suffering from a depression in which other meds only helped for awhile that this new anti-depressant helped immensely. Believe me, for me, who had 5 piles of sorted, soiled laundry on my bedroom floor for six months while taking other anti’s, Symbyax has motivated me ‘beyond belief’…within two weeks all of the clothes were taken care of, the entire apartment was organized and going into my third month of this medication, I have to bend down to pick a piece of lint up off of my carpeting. I haven’t EVER had so much motivation yet I can stop and sit or read, watch TV without feeling that I must be doing something. This does not mean that I have Bi-Polar; it just works for certain others for whom the ordinary SSRI’s don’t help. God blessed my doctor by having him keep up with the latest information and using his knowledge and discretion to help his patients, if you catch my drift!!! You may want to talk to your doc about Symbyax and give it a try if nothing else has worked so far. God bless….

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  • Depression Counseling

    Thanks to James Gordon. Here you have shown really interesting statistics on antidepressants.

  • paxil lawsuit

    A new study published in the Journal of the American Medical Association has revealed that most of the antidepressant drugs in the same class as Paxil that contain paroxetine and imipramine actually do nothing more than a placebo does.

  • Chelsea

    An interesting documentary on Walter Freeman. Let us reflect upon history in this discussion of modern antidepressants.

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