Science

Prozac Schmozac

According to an article in The Guardian, Prozac, the bestselling antidepressant taken by 40 million people worldwide, doesn’t work.

How depressing.

I know I’m depressed. Not because my medication doesn’t work, but because I own shares of Eli Lilly, the manufacturer of Prozac.

Okay, all silly and painfully obvious jokes aside (for now), the article cites a study published by the Public Library of Science that compared the effect on patients taking the drugs with those given a placebo. Apparently when the comparisons were made, no significant differences were found among the two groups. Patients given Prozac had in fact improved, but so had those given a placebo. 

However, an apparent anomaly arose in the most severely depressed patients, suggesting that Prozac may not need to go away completely. The antidepressants seemed to work for them.

But according to one of the study’s authors, Prof Irving Kirsch from the department of psychology at Hull University, the success observed in severe patients is probably because the placebo stopped working so well, rather than the drugs having worked better. Still, there seems to be some benefit for those with severe clinical depression.

Says Kirsch:

“Given these results, there seems little reason to prescribe antidepressant medication to any but the most severely depressed patients, unless alternative treatments have failed.”

So it seems not all of the 40 million plus people that have taken, or are taking, Prozac need to be.

And Prozac is not be the only drug to come under fire from this study. By all accounts, the trial was comprehensive, breaking new ground because for the first time the authors obtained a full set of trial data for four antidepressants. And the results for fluoxetine (Prozac), paroxetine (Seroxat), venlafaxine (Effexor) and nefazodone (Serzone) were all consistent.

Meanwhile, Eli Lilly and the manufacturers of the other drugs cited in the study are scrambling to implement damage control.

Sam Ogden

Sam Ogden is a writer, beach bum, and songwriter living in Houston, Texas, but he may be found scratching himself at many points across the globe. Follow him on Twitter @SamOgden

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36 Comments

  1. This is depressing, and depressingly weird timing for me… Anyhow, it kind of syncs with recent research I'd seen suggesting that a combination of drug therapy and counseling was more effective than drugs alone and counseling alone.

    I'd be interested to see if this is true of second generation SSRIs like Zoloft and Paxil. I don't know a whole heck of a lot about psychopharmacology, but I'm definitely listening.

  2. I'm not sure if I'm ready to write off these antidepressants yet, as it was my understanding that much of this data was pulled together from a variety of studies, none of which I've seen. But I've learned enough to wonder about the validity of any metastudies I encounter before I take 'em as fact.

  3. But according to one of the study’s authors, Prof Irving Kirsch from the department of psychology at Hull University, the success observed in severe patients is probably because the placebo stopped working so well, rather than the drugs having worked better.

    Pardon my ignorance, but what is the difference? If the drugs keep working when the placebo doesn't, doesn't that mean that the drug is more effective than the placebo?

  4. Elyse, the statement they made was regarding the scores taken from the studies and the ratio of drug to placebo difference. They assert that the larger drug to placebo difference had to do with a lessening of the effect of placebo on severely depressed patients, and not on an increased effectiveness of any drug.

    As regards the validity of this meta analysis. It looks like they took their data directly from the effectiveness studies that were submitted to the FDA.

    I'm not qualified to give a professional opinion but this study looks pretty clean.

  5. Oh gosh, perhaps I'm just being silly, but he has published similar in the past here

    . We should all also be aware that this guy is obsessed with finding a placebo effect in antidepressants. Secondly, the claim is that all of the data is from FDA trials, and the drugs got passed by the FDA with a degree of efficacy, then how does his compiled data come up with the fact that they're statistically not significant? Just a couple thoughts. Happy Tuesday all!

  6. the drugs got passed by the FDA with a degree of efficacy, then how does his compiled data come up with the fact that they’re statistically not significant?

    I was going to ask that same question. How did these drugs get FDA approval if they couldn't pass placebo controlled trials?

  7. We learn, we readjust our opinions and learn more. Dogmatic opinions are usually not useful when trying to apply science and given the amount of time many folk have been on these medications a large number of people are likely to hold strong opinions about their efficacy that may not be based on real benefits of the medications. We need to be willing to change our minds given the weight of reliable evidence. It’s likely that this study is a significant step toward new prescribing guidelines or a strong impetus to have more independent studies with regard to certain classes of medications.

  8. It just seems that with a meta analysis ( or as Mark Crislips says meta analysis, shmeta analysis ) you need to take the results with a grain of salt. This just would open the door to more study and like kevyjohny said how did it get through the FDA testing with a degree of efficacy. Something doesn't sound right.

  9. Scientology is going to take advantage of this more than anyone else.

    Exactly. I was trying to find SOME kind of link between this experimenter, and homeopathy, or Xenu: Warrior Alien, or anything equally pleasant.

  10. Also… I declare the need for a Skepchick/geek chatroom! I'm sure that there are sometimes late at night when we are working on serious amounts of work/homework and want to procrastinate with our fellow nay-sayers. I'm sure, if you'd like that, we could find a script for one for freeeeeeeee.

  11. My understanding has been that there have been studies in the past that indicate that exercise is better for mildly depressed persons than antidepressants. The difficulty comes in deciding who is mildly depressed and who is not. I do think there are times that there is over prescribing of antidepressants especially for women (I have seen men who I thought were clinically depressed but their doctors weren't treating them for that) (I am a physiotherapist and have seen many men and women over the years who while suffering pain also seemed to be depressed but there was nothing I could do about it except in a very round about way as I am not qualified to make that kind of diagnosis) I think this study adds to our understanding of the whole arena of antidepressant use but as always more study is needed.

  12. The accuracy of metaanalysis aside, if 40 million people are taking a certain class of drug, is it maybe overprescribed? Maybe there is a [smaller] group of genuinely depressed people SSRI's can help, and a whole of lot of morose, weary, or malingering people popping SSRI's because that's been the common tool in the box to treat the problem of depression.

  13. If the drug does help deep depressives…what does that say about all the people who perked up just as much over a placebo?

    I think that's the only major argument in favor of continued use of the various antidepressants.

    In less severe patients, there was no discernable difference between the placebo group and the Prozac group.

    However, placebos ceased to be effective for severely depressed patients after a period of time, while patients receiving the drug actually maintained levels of improvement.

    So the argument now, at least in light of this finding, is that antidepressants should only be prescribed for severe patients.

  14. So the argument now, at least in light of this finding, is that antidepressants should only be prescribed for severe patients.

    Which raises the question about all the other more mildly depressed people who wouldn't be getting their drugs, then. If the mere IDEA of the drug helps them, should it still be OK for them to continue with their prescriptions? Does it matter if it's the drug itself or just the idea of it, as long as it helps?

    For myself, I'd want to know if it was just the concept of the drug that was helping instead of the drug itself, which is why I managed to avoid being prescribed anything when I went through a period of depression a few years back — mine was treatable through light therapy and exercise, and I've always been glad I didn't end up with a psychological dependence on an antidepressant.

    But I have several friends and acquaintances who are firm believers in them, and they would be MOST displeased to have to go off them, or to be told that it had been a placebo effect all along. For them, it works, whether it's chemical or psychological — which makes me wonder (for them) if it really matters which it is.

  15. Therapist here,

    Regardless of whether the effectiveness is due to placebo or not, people should be careful about coming off of SSRI's cold turkey if they plan on stopping. Probably should consult your psychiatrist or PCP (although PCP is more likely to give less than a therapeutic dosage), before going off SSRI's, or else risk feeling worse than if you never started taking anything in the first place.

  16. Also… I declare the need for a Skepchick/geek chatroom! I’m sure that there are sometimes late at night when we are working on serious amounts of work/homework and want to procrastinate with our fellow nay-sayers. I’m sure, if you’d like that, we could find a script for one for freeeeeeeee.

    I suuport it.

  17. I am more than a little suspicious about these findings. First it's a metaanalysis, which have real problems associated with them. Secondly why is this published in the 'Public Library of Science'? Perhaps I am ignorant for not having heard of it, but surely such groundbreaking research should have made it into one of the major psychiatry or medical journals. I wonder if one of the guys at Sciencebasedmedicine.org will write something on it.

  18. Improbable Bee wrote:

    Which raises the question about all the other more mildly depressed people who wouldn’t be getting their drugs, then. If the mere IDEA of the drug helps them, should it still be OK for them to continue with their prescriptions? Does it matter if it’s the drug itself or just the idea of it, as long as it helps?

    This is the one argument homeopathists never seem to grasp. Yes, it might all just be your imagination, but dammit doesn't that make your imagination a very interesting subject to study? With some luck, we might be able to employ the placebo effect to achieve some real results. There lies the true "healing power of the brain".

  19. Improbable Bee wrote:

    Which raises the question about all the other more mildly depressed people who wouldn’t be getting their drugs, then. If the mere IDEA of the drug helps them, should it still be OK for them to continue with their prescriptions? Does it matter if it’s the drug itself or just the idea of it, as long as it helps?

    Well, and I come back to the fact that even if the effects are due to the placebo effect, the side-effects are likely not (though some of them likely are…) Frankly, taking my placebo with a side effect of weight gain, total lack of sex drive, and inability to cry is not real appealing.

  20. Also, as an fyi, we’ve known for a long time that exercise is just as effective in treating mild depression as drugs. (Yea for endorphins.)

    This actually wasn't true for me; I don't know if it's because I was already exercising regularly and had been for years. In fact, one of the symptoms of depression for me tends to be that the whole endorphin effect of exercise quits working for me.

    I could totally see exercise having quite an effect if you started a new exercise regimen after becoming depressed. So my experience is anecdotal but I'm curious as to whether anyone has looked at that.

  21. Total lack of sex drive? Now wouldn’t that just transfer the depression from you onto your husband?

    Actually, all kidding aside, aren’t those common observances among recent mothers? Just wondering …

    Not exactly. Lack of sex drive, yes, but that is a commonly reported side effect for both genders, especially with Zoloft. I did not personally experience weight gain postpartum, quite the opposite (which is the more common scenario, especially if breastfeeding), and inability to cry is also quite the opposite of usual postpartum experience, and was more a result of the sort of emotional "plateau" type effect you can experience on SSRI's. Now, it also depends on what you consider the postpartum period. I wasn't treated for PPD until about 4 months postpartum. So I was actually citing those side-effects as more general and not just as my personal experience. Many of the people I know on SSRI's who have experienced these type of side effects are neither female nor recently postpartum…

  22. That said, considering the side effects, wouldn’t that make anti-depressants a good drug to take for PPD? Seeing how the natural responses counteract the side-effects …

    Eh. I mean, weight loss is a GOOD thing when you're postpartum. I don't think the weight gain thing happens for everyone. As for anti-depressants keeping you from crying all the time, yes, that is definitely a good thing. :)

    Zoloft in particular is often prescribed because it's considered safe(er) for breastfeeding. Placebo or not, feeling better when you've got a little one is a good thing, don't get me wrong.

    All I was getting at is that for most people, a) even if the positive effects of anti-depressants are a placebo, the side effects may be quite real and b) the platitude that exercise is just as effective for mild depression (which I know the Scientologists love) might not be true in all cases.

    And thanks for thinking of my dear, dear, hubby, Exarch. :) He weathered it all just fine.

  23. I could totally see exercise having quite an effect if you started a new exercise regimen after becoming depressed. So my experience is anecdotal but I’m curious as to whether anyone has looked at that.

    I'd have to check, but I'm betting the studies were done with assigning random groups: control, exercise, drug. If that's the case then it would have been for those not on a previous exercise plan.

    Some poking around on PubMed would probably come up with a few papers on exercise before depression.

  24. Some poking around on PubMed would probably come up with a few papers on exercise before depression.

    But then I'd have to admit to myself that I'm actually frogging around on the internets and not working. But I am curious enough to check it out later on. Thanks!

  25. I don’t enjoy defending big pharma, but I wonder at the validity of this study as it is a meta analysis and other papers published by Irving Kirsch in PubMed are:
    “Placebo analgesia: findings from brain imaging studies and emerging hypotheses”
    “Hypnotic history: a reply to critics”
    “Illness by suggestion: expectancy, modeling, and gender in the production of psychosomatic symptoms”
    “Remembrance of hypnosis past”
    “Clinical trials and the response rate illusion”
    “Effects of misleading questions and hypnotic memory suggestion on memory reports: a signal-detection analysis”
    “Suggestion reduces the stroop effect”
    …and it goes on.

    There’s a really good write up at badscience.net that goes into both sides of the issues.

    Also, as an fyi, we’ve known for a long time that exercise is just as effective in treating mild depression as drugs. (Yea for endorphins.)

  26. Frankly, taking my placebo with a side effect of weight gain, total lack of sex drive, and inability to cry is not real appealing.

    Total lack of sex drive? Now wouldn’t that just transfer the depression from you onto your husband?

    Actually, all kidding aside, aren’t those common observances among recent mothers? Just wondering …

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