Antidepressants Do Work Well — We’ve Simply Been Evaluating Them Incorrectly

Rob Wipond
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The reason that SSRI antidepressants have seemingly not performed better than placebo is because their effects have been measured incorrectly, according to a reanalysis of clinical trial data published in Molecular Psychiatry. A more appropriate way to measure SSRI efficacy, the researchers argued, is to ignore the answers to 16 of the 17 questions about patients’ feelings that were typically asked during the drug trials.

“The recent questioning of the antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is partly based on the observation that approximately half of company-sponsored trials have failed to reveal a significant difference between active drug and placebo,” explained the team of researchers from the University of Gothenburg in Sweden. “Most of these have applied the Hamilton depression rating scale to assess symptom severity, the sum score for its 17 items (HDRS-17-sum) serving as effect parameter.”

The University of Gothenburg researchers chose to focus instead on the answers to just one of the 17 questions from the common depression rating scale. The question they chose was the one in which patients are rated by clinicians on their overall “depressed mood,” or feelings of “sadness, hopeless, helpless, worthless.” According to a copy of the test posted by the National Institute of Health, other questions on the HDRS-17, which the researchers decided to ignore, revolve around topics like suicidal feelings, insomnia and struggles to work.

Answers to the question about “depressed mood” are entered on a scale of 0-4, where 0 is “Absent” and 4 is “Patient reports virtually only these feeling states in his/her spontaneous verbal and non-verbal communication.” Evaluating only the answers to this one question, the researchers found that the SSRIs seemed to have stronger positive effects than placebo in 29 out of the 32 clinical trials they examined. Placebo also produced positive scores on the answers to this question in most of the trials, but by fractions of a point less overall.

“While not claiming that assessing depressed mood only is the optimal way of recording symptom severity, or that other symptoms are irrelevant, we do suggest that a treatment faithfully outperforming placebo in reducing depressed mood can hardly be regarded as ineffective,” wrote the authors. They concluded that the reason SSRIs have seemed to fail to outperform placebo in clinical trials is due to an “insensitive measure of efficacy.”

Hieronymus, F., J. F. Emilsson, S. Nilsson, and E. Eriksson. “Consistent Superiority of Selective Serotonin Reuptake Inhibitors over Placebo in Reducing Depressed Mood in Patients with Major Depression.” Molecular Psychiatry, April 28, 2015. doi:10.1038/mp.2015.53. (Full text)

Hamilton Depression Rating Scale (HDRS) (National Institute of Health)

34 COMMENTS

    • Actually, in reading this check list for depression, it’s no wonder so many are being diagnosed as depressed. And this checklist does not describe a specific illness, it describes life’s normal frustrations, at any particular point, within every human.

      According to this depression check list, it seems anyone suffering from sadness, guilt, frustrations of any kind including at work, which is common, insomnia, retardation, any kind of agitation whatsoever, warranted or not, unexpressed fears or worrying about small matters (which is apparently considered “anxiety psychotic” – thus a potentially major mental illness), any kind of actual physical symptoms (which is considered “anxiety somatic” – also likely claimed to be one of the major mental illnesses), gastro-intestonal symptoms, any kind of backaches, head aches, muscles aches or fatigue, loss of libido, PMS, any medical complaint whatsoever (which is claimed to be hypochondria), any loss of weight, even upon the recommendation of a doctor.

      These are the “symptoms” for a “depression” diagnosis, according to this checklist. These are also the “symptoms” of being a human being.

      I’m shocked the psychiatric industry published this. It’s so ridiculous it staggers my mind.

      And the antidepressants don’t work for smoking cessation, but antidepressant discontinuation syndrome symptoms do get misdiagnosed as ‘bipolar.’ What a sick joke the psycho / pharmaceutical industries have made of the entire mainstream medical industry.

  1. Last listed, but corresponding and apparently senior author: “Correspondence: Professor E Eriksson, Department of Pharmacology, Sahlgrenska Academy, University of Gothenburg, POB 432, Gothenburg SE 405 30, Sweden. E-mail: [email protected]” AND, guess what? “Conflict of interest… Elias Eriksson has been on advisory boards and/or received speaker’s honoraria from Eli Lilly and H Lundbeck.”

  2. If anti depressants really did work they would be destructive to humanity because people could be happy without having to do anything.

    The Original Star Trek episode “This Side of Paradise” was sort of a cautionary tale about this.

    Think about what would happen if people no longer had depressed moods.

  3. The writeup of this seems a little unclear. Regarding Someone Else’s question, above, I’m pretty sure all the questions at issue here are answered by the patient and that what this summary refers to as “clinician rating” is simply the clinician’s scoring of all the patient-answered questions together. No?

    Although I am, as always, alarmed by the authors’ drug company affiliations, and place myself firmly in the anti-SSRI camp, it seems to me there is something important to pay attention to here. Is there not something valid in their paying attention to the question about actual feelings of “depression” (sadness, hopelessness, etc.) and not the ones about insomnia, work life, etc.? Is it possible that this shift of focus helps explain the disparity between previous studies like this suggesting minimal effect and the fact that so many people say that SSRIs have helped them dramatically?

    Of course, all that begs the question of why no one has looked at this before, and I realize it may be just another attempt at legitimation. Still, if anyone here can shed more light on whether there really is something of value in this piece of research I’d love to know.

    • Danny:

      I’m not sure what your point is but I want to understand it. Could you reframe this? Are you suggesting that that there is a huge disparity between what clinicians are observing after administering SSRI’s and what patients are reporting after using SSRI’s? If so, I am unaware of this disparity. If I had to guess, I would predict that clinicians tend to report overly optimistic findings (unless they are participating in a double blind study) not the patients because patients often are afraid to appear resistant to treatment and have this strange desire to ‘please’ their provider. Could you please describe this disparity in greater detail? (are you referring to a study and if so, could you offer a citation) Are you saying that ignoring the sixteen questions about sleep, work, etc. and focusing on the single question having to do with “feelings” of depression is resulting in some kind of explanation for this disparity in findings, about which I don’t know anything?

      • Hello Madmom,

        My wording may have suggested more of a disparity than I intended. I have not made a terribly close study of it, but I’ve been inclined on the whole to buy what we’ve heard from people like Irving Kirsch, that if you look at the full scope of the data (e.g., if you include studies that drug companies withheld from publication) the supposed (never all that great) effectiveness of SSRIs mostly disappears. i.e., they are hardly better than placebo–on average, of course, at the level of a population examined in research. But then there are many individuals who say they have been helped a great deal by the drugs, and clinicians who say they see this in many of their patients. (For instance, if you look in the comment sections of articles and editorials in the NYTimes on SRRIs you find a preponderence of people writing in and saying that they have benefited, that the drugs “saved my life,” etc.)

        That’s what I was referring to as a disparity. (I know only too well there’s another, less publicized, side of this coming from people, like me, who’ve been harmed a great deal by the drugs.) I’ve tended to think all this could be simply because the drugs make some people feel better and some worse, so on average there’s little effect (as Kirsch et al. say) but some people find them helpful and insist they “work”…and of course that’s the mainstream narrative and so it gets more press and more validation. It’s seemed to me that this all could be because the drugs have fairly random effects and some people just luck out, or maybe because the placebo effect works better for some than others. (I assume negative experiences do not come from placebo effect.) Of course, individual differences like that get little attention in the research literature (there it’s all averages and statistical significance), which makes it tougher to interpret those individual accounts.

        What I wondered about this article is whether it might show that, if you only measure for what I’ll call the “core” of depressive symptoms (sadness, etc.) and not all those others (insomnia, etc.), MAYbe SSRIs actually are effective, at least on a single symptom measure and over the short run, which would line up better with some of those individual accounts. It wouldn’t, however, at all negate side effects, lack of efficacy (or negative efficacy) over longer time periods, or the likelihood that non-drug approaches may be just as effective, or more so over the long haul.

        So them’s my thoughts, such as they are. Mostly I’d just like to understand it better. Thanks for asking!

        • the article above says, “Placebo also produced positive scores on the answers to this question in most of the trials, but by fractions of a point less overall.”

          This could indicate an active placebo response to the SSRI as, if i read this right, the improvement on SSRI’s over placebo is small.

          • Exactly. The one measure that is MOST likely to respond to placebo is “do you feel better?” It’s harder to say that you’re sleeping well when you’re not, etc., but the “feelings of depression” question they choose to focus on is probably the most vague in the questionnaire.

            It’s also VERY bad science to change the measurement used after the experiment is done. If they believe this, they would have to design and conduct another series of experiments and use this as their only measurement, and report on the results. It’s not OK to re-interpret results after the fact in any scientific study, as it enables you to choose the variable that you already know has changed in the direction you want it to. Which is exactly what they are doing here. It’s totally bogus and clearly just an effort to justify what they already believe.

            —- Steve

        • Hi Danny. I’d like to add a thought regarding the disparity you noted between the science showing antidepressants don’t work very well, and reports of many users claiming the drugs worked for them. Although these observations seem disparate, to my mind they are not. The reason why is that the placebo effect in depression is large. People who take antidepressants, on average (with lots of individual variation around that average, to be sure), experience moderate improvement. This improvement is real, and is mostly a product of the placebo effect.

          What complicates discussions about antidepressants is that we’re working with two different and popular conceptions of what it means for a drug to “work.” Scientists say that a drug “works” if it is reliably better than placebo. Antidepressants are not, especially in young people. But people who take drugs say drugs “work” when they produce the desired effect, and antidepressants do make most people feel less depressed. The large placebo effect in depression helps to explain why antidepressants simultaneously appear to “not work” (to scientists) and “work” (to users).

          • Thanks, Brett. This makes a lot of sense. I am so struck by the lack of attention to these differences–between the dominant research model, averages across populations, on the one hand, and qualitative measures, individual experience, clinical judgement, on the other. Surely there must be people looking at how to bring the two together (and good clinicians do it all the time) but you just never hear much discussion of it and I always wonder how much attention it does get, say, in the training of doctors, therapists, etc. My guess is, not nearly enough.

            Part of what is driving me on this is, despite my belief that these substances are mostly just bad, I feel we need to be careful not to discount the experience of people who have suffered but have experiences different from our own–we, being most on this site. Given all of the above, if we assume placebo is the primary action on the whole, are we sure there are not individuals who are not “really” benefitting, i.e., beyond placebo. How do we judge or sort out all those very individual accounts, and the clinical judgement of professionals working in this area. I want to be very clear that I am not assuming anything substantive with this but rather wondering about process and wanting to make certain we do not risk throwing any babies out with the bathwater. I want to make sure no sincere voices or real effects on the other side are left out (in the way those on our side routinely are) and also feel that the more thorough we are in this respect, the more credibility we have.

          • I’m not sure I understand how the placebo response plays out in the real world when you have people who need to try multiple ADs to find one that works. Even with the poop-out effect confuses me. Seems odd that one day someone just decides to stop believing they work. Although that does have a bit more plausibility.

            Nor does it seem to account for someone like me who doesn’t think any med or supplement works until proven otherwise by trial and error. I’m actually quite surprised when any of them do.

            No, I don’t take ADs, but I have been through various sleep meds taken as needed, and I’m positive 5htp has an effect on the quality of my sleep/dreams.

        • Danny

          And what is usually not mentioned is that these drugs often poop out and quit “working” even for the people that claim that they saved their lives. The dosages have to be increased to absolutely insane levels, people claim that they’re working again, and then the poop out shows up again.

    • Yes antidepressants make people drug happy, and they last for 10-20 years max……../ if you are lucky, then they dont work, you have to go off them, you suffer severe, severe illness, worse than “social anxiety”… by then you got stuffed heart, suffed liver, stuffed kidneys…. but damn, you get your brain back, like awakening from a dream, you laugh again, you cry again……….. Antidepresessants help? Who, the happy person who leaves the psychs office after 6 weeks???, he never sees the mess, when they fail, as they all do.

  4. If you do a certain number of scientific research and leave the data alone for 20 years. Then go back and re-evaluate the data, but adjust the questions or the ‘angle’ of the questions. The answers you will find 20 years later will be different.

    Adjusting the questions to fit your desired answer cannot be called ‘science’?

    I wrote to this professor, since he is also Swedish, but I doubt he will answer.
    I’m so ashamed. How come my Little country could be so involved in this 30-year-scam?
    It must be some kind of “kid-sibling-complex”, small country wanna do big impact.

  5. The conclusions of the researchers of the University of Gothenburg are far from being objective.

    If depression could be cured thanks to the temporary elimination of a few symptoms, a bottle of wine would be one of the best antidepressants of the world.

    Depression must be cured based on psychotherapy. This is an obvious truth that everyone should know, but the pharmaceutical companies that are making a lot of money thanks to the production of useless and dangerous drugs (and the psychiatrists who prescribe these drugs to the ignorant patients who trust them) don’t let the public understand the truth.

    • Problem is antidepressants are handed out like lollies… Husband died? Upset after 2 weeks, ah antidepressants… Feel shy in public? Social phobia, take antidepressants…. then try and go off them, they are damn more addictive than heroin… result, sever major anxiety and depression, suicidal thoughts, when you never had them before drugs. Big Pharma, drug dealers beyond belief…. now they even testing ecstacy as an antidepressant? What? Cant buy it illegally, but take it from your local drug dealer doctor, the psych? Addicts…… and to kick the habit, it is damn hard.

    • I was conned, absolutely conned………………. Psychiatrists are arrogant and ignorant, self important idiots. What a profession? They can lock people up and forcibly medicate them (even though it was their treatment that failed)…….they can add drugs, the drugs make you worse?? no, they say, no it is an underlying what is the one at present? Oh, underlying bipolar.. get sicker, ah underlying psychosis, get sicker, ah underlying…. never ever their treatment failure? The drugs that have never been tested beyond 6 weeks? Arrogant and ignorant. And full of self importance, and who dares question a damn psychiatrist? I reckon they have more fun than crooked cops.

      • And best of all psychiatrists dont have to “prove” their diagnosis to anyone………. more powerful than witch doctors, well that is basically what they are? They control your mind, make you submissive, and destroy your life. And who gives them all the freebies in their cupboard? Big Pharma, yep I was a victim on zoloft baby birth defects… Given the “freebies”out fo the cupboard, before the damn drug was even passed for use. We are human guinea pigs, lab rats……… obscene!

        • Give me a witch doctor anytime over a psychiatrist.

          When I began my journey into the so-called “mental health system” I was held in a medical hospital after trying to kill myself. We didn’t have a psych hospital or unit in the city where I lived so everyone is held in an ICU unit in a med hospital until a bed opens up at the state “hospital”. The nurses wouldn’t talk to me because I’d tried to kill myself.

          But, one morning I woke up to see the face of a beautiful, auburn haired young woman nurse looking back at me. She smiled and said that she was glad that I was awake. She’d been sitting quietly for ten minutes waiting for me to wake up, she didn’t want to startle me out of sleep. As she got the things ready for me to take care of my ADL’s I noticed that she was wearing mala beads wrapped around her wrist, what you might call a Buddhist rosary. I mentioned the beads by name and she stopped what she was doing, looked at me and said, “You know what these are?!” I laughed and stated that I was Buddhist so of course I knew what the beads were. She asked if she could come back and spend some time with me after she got her duties taken care of for the other patients on the unit and I said she’d be very welcome to come back and talk with me. I’d been there five days and no one talked to or with me. We spent about 45 minutes together during which she told me, in great secrecy, that she was a Wiccan, what some people call a “witch”. She begged me not to tell any of the other nurses because she would lose her job du to bigotry (I live in a very backward state here in America). She listened respectfully to my story as to what brought me to wanting to kill myself. No one had bothered to find out up to that time. It was one of the kindest things I’ve ever experienced on this “journey” of my “mental illness”. She valued my story, listened intently and deeply to me, and then shared some very wise observations. She was the beginnings of my desire to live again. So, I say, if that’s what “witches” are like then give me more “witches”!!!!!!!

          Sorry for sharing such a long story but talking about witch doctors reminded me of this very important experience of mine. Not one of the five psychiatrist who worked on my “case” ever asked me why I tried to kill myself. Only this Wiccan and one student nurse ever cared enough to try to find out what caused me to try to do what I did. These two were more therapeutic for me than all of the doctors and nurses that I’ve dealt with on my Journey! So, give me more witch doctors! They’re actually of some use to me!

  6. It is also hard to evaluate the efficacy of antidepressants. They do have an effect on our brains otherwise we wouldn’t have such withdrawal effect or they would not be able to cause adverse symtoms like mania. However, there are a lot of speculations about how exactly they work. The chemical imbalance theory is being disproven and inflammation seems to have a major role in mental illnesses and almost every disease. The question is what causes the inflammation ? Probably both physical and psychological reasons. Being under stress has an effect on your immune system and thus on disease. Diseases are just so more complex than the medical community wants us to believe. (especially the mental health community). It just baffles me that people with mental illnesses don’t get a full health examinations but instead get described pills that may or may not work and that not tackle the root cause. Mental health is both physical as psychological but as very little to do with being deficient in serotonin.

    Placebo, natural improvempent of mood, getting attention, … can all be helping with depression instead of the drug in the trials.

  7. I also think there is a huge pressure for humans who don’t feel so well to fit a certain category for illness.
    For example will feel really tired suddenly experience brain fog, stomach problems other ills and will go to the doctor the doctor will do a very random check up and will not find anything. However the persons symptoms will not go away and the doctor will suggest depression and because we have learned that we need a diagnosis to justify feeling bad the patient will embrace the term. We need diagnosises to justify ourselves to society for not performing like we should. And because the medical science has this tendency to call every thing they can’t explain mental, many depression diagnosises will be made. Furthermore, you need a diagnosis to justify your absence at work or school. You can’t just say sorry but I don’t know what is wrong but I feel like shit and can’t come to work.
    The way psychiatry is today is very logical, it fits perfectly in our modern society. Diagnosises will only drop when societal pressure to be productive will drop. And they will only drop when the social aspects in society regains his importance again. We are social animals so we need a social society.
    Many people have lousy jobs, they may be lonely, they don’t fit in and illness is there only way out. Often depression and axiety is the only way they know how to “deal” with there problems. We need to learn alternatives to dealing with emotions.

    (sorry for poor grammar or spelling I am not stupid 🙂 I am just not English speaking)

  8. groentje:

    This comment needs to be copied (after a few typos are fixed) verbatim and sent to every editor of every daily newspaper, church newsletter, and medical jourmal in the US. Don’t change or add a single thing; This is one of the best comments I’ve read on this site, ever. It needs to be circulated far and wide and shouted from the mountaintops. Thanks for sharing groentje.

    Sarah