Is There a Small Group for Whom Antidepressants Are Effective?

In a new study, researchers found no evidence of antidepressant group variance, which means that there's no particular group of patients who improve more than others on the drug.


In a new study, researchers tested the theory that some groups of people might improve dramatically on antidepressants, while others fail to improve. Their analysis found no support for such antidepressant group variance. Instead, they found that all patients experience about the same minimal effect from antidepressants.

“No or only very small subgroups of patients respond particularly well to antidepressants. Thus, the scope for personalised treatment with antidepressants seems to be limited,” the researchers write.

one yellow game piece among blue game pieces
Photo credit: Marco Verch, CC BY 2.0

In recent years, some researchers proposed a theory: that the average slight effect (over placebo) of antidepressants might be due to a group of patients that benefit highly, while other people do not benefit at all, experiencing just the adverse effects of the drug. The two groups would cancel each other out, leading to the minimal average improvement seen in drug trials.

If this were true, and the subgroup that benefitted from the drug could be identified, then doctors could prescribe the drug only to those who would improve after taking it. This would reduce the number of people who take the drug and experience no improvement, worsening experiences of depression and anxiety, and/or the harmful effects of the drug.

Unfortunately, no such subgroups have yet been found in previous research. The researchers write that “Despite substantial research efforts, no predictors of treatment success with ADs were found that were robust and reliable enough for use in clinical practice.”

And now the theory itself has just been debunked, according to a study published in BMJ Open.

Researchers Martin Plöderl and Michael P. Hengartner conducted the first-ever study to test the underlying theory of antidepressant group variance. Their statistical analysis included both published and unpublished antidepressant trials to avoid the trap of publication bias (positive results are more likely to be published). They write that their dataset “is one of the largest so far, resulting in precise estimations of the main outcomes.” It included 169 clinical trials of various antidepressants for people with a diagnosis of major depressive disorder.

If the theory were true, then the variance within the antidepressant group should be larger than that in the placebo group. If the drug worked for some people, but didn’t work for others because of biological differences, then some people would experience no change, but others would have significant improvement on a depression scale. No such difference should be found in the placebo group, as there is no drug x biology interaction in that group.

Plöderl and Hengartner tested this by comparing the variance within the antidepressant group to the variance within the placebo group. They found that the two variances were virtually the same. This means that the antidepressant group did not, in fact, have the large variance predicted by the theory. The simplest explanation is again the most likely: antidepressants are only slightly better than placebo for almost everyone.

The researchers then ran a simulation to test whether similar variances (VRs) could happen even if the theory was true. But their simulation found that if the theory was true, there was no way it could lead to such findings. They write, “Our simulation analysis confirmed that equal VRs can only be obtained if there are not more than a few patients who respond slightly above average.”

There are still some peculiar and unlikely explanations that could also lead to this finding. For instance, it might also be found if there was a tiny group of “super responder” patients who did incredibly well. But this should lead to severely non-normal distribution of scores, which has not been detected in any statistical analysis to date.

Although each successive class of antidepressant medication has been initially touted in industry-funded studies as powerful treatment for mental illness, further research has consistently found that their effects are minimal when compared with placebo. When published and unpublished data are included, researchers found that about half (49%) of the trials of antidepressants actually show no benefit over placebo for the drug. More recently, multiple peer reviewed articles from last year found that the placebo effect may account for almost all of the improvement supposedly due to antidepressants.

According to Plöderl and Hengartner, “With the ADs currently available, the scope for personalised AD treatments is probably limited and it is unlikely that precision psychiatry will succeed in finding clinical or biological predictors of differential treatment response that would account for a therapeutic effect that goes beyond a minimal clinical improvement.”


Plöderl, M., & Hengartner, M. P. (2019). What are the chances for personalised treatment with antidepressants? Detection of patient-by-treatment interaction with a variance ratio meta-analysis. BMJ Open, 9(e034816). doi:10.1136/bmjopen-2019-034816 (Full text)

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Peter Simons
Peter Simons was an academic researcher in psychology. Now, as a science writer, he tries to provide the layperson with a view into the sometimes inscrutable world of psychiatric research. As an editor for blogs and personal stories at Mad in America, he prizes the accounts of those with lived experience of the psychiatric system and shares alternatives to the biomedical model.


  1. thanks Peter.

    “….unlikely that precision psychiatry will succeed in finding clinical or biological predictors of differential treatment response that would account for a therapeutic effect that goes beyond a minimal clinical improvement.”

    I’m confused. I thought precision psychiatry had found clinical relevant information on WHO would benefit.
    Was it not serotonin depletion? And in that case, since only “some” people respond or become “super responders”, how do you try to identify subgroups? Seems to me, since it is a “chemical imbalance”, one would try to identify the subgroups by measuring them for those “imbalances”? via-extracting those chemicals, placing them in balancing scales? Obviously if you propose theories, one has to measure it by the chemicals, not the drugs?
    Call me stupid.
    I am still interested how exactly the “sub groups” were chosen. By their behaviours and “symptoms”/diagnosis, or by measuring them for the chemicals.
    Lol, it is very difficult to take any part of psychiatry seriously. If they would stop labelling every part of the human experience as an illness, it could reduce the wild theories and reduce exposing the whole lot of them as quacks.
    If it takes a hundred years to notice yourself going backwards or being stuck, as a practice, perhaps one has to examine the practice.
    But so far, it is the business that keeps it going, not any evidence. And there is always new blood for the bedbugs.

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      • LOL Steve.
        Sometimes I want to make appointments with psychiatrists just to toy with them.
        A bit of payback. But I fear they are a step ahead of me, those mind readers and can probably ‘see’ what my intentions are.
        I can see psychiatry being on edge, fearing people are in there as spies. You know, since the experiment some while back, where they could not tell the dif.
        I think they just developed more paranoia since then.
        I thought I was paranoid, until I really examined what paranoia looks like.
        It would be very difficult to continue, without paranoia, in a system that harms people. A certain conspiracy theory has to underlie such narrow views of the society they feed of and participate within. Not once do they see the irony within their jobs.
        Weird and fascinating at the same time.
        Truly, I cannot fault them, but their interest lies not in others brains. That died a long time ago. They became innocents trapped in a belief. And here I am deeply interested in the kind of brain that blindly follows a belief that has the ability to harm.

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        • I don’t think most psychologists and psychiatrists are “innocents trapped in a belief.” In part because all doctors are taught in med school that both the antidepressants and antipsychotics are anticholinergic drugs, that can make people psychotic, via anticholinergic toxidrome. Resulting in the psychiatrists setting up an entire industry, with the goal of profiteering off of harming people, by making them psychotic, with those drug classes.

          As to a payback, and the psychologists, I recently had a second Lutheran psychologist sicked upon me. The first psychologist had as a goal, covering up the abuse of my child. The second one had been told I knew all about the psych drugs, and was trying to educate the “mental health” workers, so they’d stop turning millions of children into “bipolar”/”schizophrenics” with the psych drugs.

          My paternalistic childhood religion apparently doesn’t want to get rid of their child abuse covering up “mental health” minion, however. And since my artwork “too truthfully” describes that religion’s, and their “mental health” workers’, systemic child abuse covering up crimes. They wanted to steal all my work, and silence me.

          So that second Lutheran psychologist spent a bunch of time coming up with an “art manager” contract that he had hoped would allow himself to steal all profits from my work, my work, eventually all my money, not to mention take control of my story, accountants, and lawyers. You know, a slavery contract, under the guise of an “art manager” contract.

          Unfortunately for him, I wasn’t dumb enough to sign that contract. But I agree, a little payback is in order for such ungodly disrespectful and criminal behavior, at times. And since there is at least one former Lutheran who shares my disgust at the ELCA’s systemic child abuse covering up crimes, and wrote a book about these systemic crimes.

          I was able to embarrass that psychologist pretty quickly, by pointing out his religion’s, his industry’s, and the psychiatrist’s systemic child abuse covering up crimes, with a few little links.

          That’s about when this song came out.

          And, yes, that psychologist had to face the reality that, “I’m the bad guy. Duh!” The psychologists can claim the musicians don’t have muses, but that’s not what many of the musicians say, and it’s still not what it looks like to me. Ironically, that psychologist was also a musician, perhaps, aptly named “doubting” Thomas?

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  2. This trial was bound to fail, given the molecular nature of “depressions”, which are likely to be as varied as the other “mental disorders”. They’re in the same league as the Michigan shrinks many years ago, who couldn’t understand why a state hospital’s “schizophrenic” patient’s hair turned green (Wilson’s Disease should be coming to mind for you MIA MD’s).

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    • They stopped being interested in MI eons ago.
      It shifted into a belief system where now spoiled cranky brats go to college to
      learn about “diagnosis” and “disorders”, NOT about the human condition.
      The disinterested, disillusioned, discontent are in “practice”. And this practice
      has zero to do with integration or acceptance, not unless a shrink kindly allows acceptance lol.
      We can walk the trail of shrinkage back and forth and come up with nothing good that came out of it.
      IF there is any interest left within psychiatry, I am at a loss of where it exists. And as long as “interest” lies in wanting to make others in the image of ourselves, then we are indeed doomed.

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  3. “Is There a Small Group for Whom Antidepressants Are Effective?”

    The simple answer is no, but define “effective.” Then define “antidepressant.”

    If by effective we mean the increase in suicides, then yes, “antidepressants” are very effective.

    But even the word “antidepressant” is misleading, because it hinges on the chemical imbalance hoax. There is no chemical that corrects a supposed chemical imbalance.

    “Antidepressants” are, in reality, dangerous, brain disabling, chemical compounds. Peter Breggin has repeatedly shown that most supposed “benefits” from so-called “antidepressants” arise from the effect of medication spellbinding.

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    • I’ll play devil’s advocate.
      Do drugs called “antidepressants” ever make people feel good? Yes they do.

      I enjoyed two SSRIs when I first went on them.

      I took Anafranil back in 1993 because of intrusive thoughts brought on by anxiety. It felt good at first–but like a horror movie it soon turned scary. The buzz turned into full blown hallucinations and I didn’t sleep the whole 3 weeks I took it.

      After getting put on massive amounts of neuroleptics and kicked out of college because of seizures and other stuff, I became suicidal in 1994. They put me on Zoloft. It too gave me a buzz–but mild enough I could control it.

      I didn’t need a buzz, but friendships and a purpose in life.

      So, if someone says, “These antidepressants make me feel great. They ended my depression,” I agree with them. They are probably right.

      Any “upper” from a street dealer could have similar benefits though.

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      • From my observation, antidepressants essentially induce a manic-like state, where a person is more spontaneous and less concerned about consequences. A friend of mine called it “Zolofting.” It’s kind of a “who gives a f*&k” attitude that can feel really good, especially for someone who has always been worried a lot about what other people think or feel about them. But as with all drugs, messing with the neurotransmitter system, however good it might feel, has long-term consequences that are often quite destructive. Some people seem to be able to tolerate them long term, but it’s a very risk way to “feel good,” and of course, does nothing to address why you might have been feeling bad in the first place.

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  4. Jordan Peterson (the Canadian teacher who was threatening to go on a hunger strike because of pro-nouns) swears by SSRI’s (in combination with Wellbutrin). Could it be that he is so volatile (or dull?) (emotionally) that increasing serotonin in his brain (until the brain compensates, which it eventually does) is like a vision of god? He does have 4 full-time jobs. That’s a 32 hour working day …

    Just try it man, what have you got to lose? So says the drug dealer.

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  5. Part of the problem is that there can be no satisfactory or even sensible answers when people ask the wrong questions. What is meant by “effective” — that people are no longer suffering because the switchboard in their brain which alerts them to the fact that they are suffering has been short circuited? I imagine there are a number of psych drugs which are effective at that. They also make it easier for mass shooters to feel like they’re playing a video game.

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    • My mother and sister-in-law swear by theirs. Doctors prescribe them. Doctors never make mistakes or lie.

      At least they enjoy some placebo effect.

      Mom has become like a zombie after ten years on at least one SSRI. Complains of feeling “meh” and joyless.

      My sister-in-law breaks down into tears she can’t control from time to time. I have seen Jordan Peterson go through a similar break down.

      Truly sad.

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    • seeing as I can’t reply yet, the comment, other one not actually approved of, would here say:

      There are better ways of going psychotic, in order to be deemed a non reliable source, just in case you’ve got the nerve to get yourself into obliviousness, but it’s of course really about aliens with spaceships that come and pick you up, if you’re in need of an air lift, and on anti-depressants, because I really don’t think that you would get shipped over to the USA, just because Russia wanted you treated right.

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  6. ….WTF?….”precision psychiatry”? That makes as much sense as “random specificity”. In other words, it’s NONSENSE….
    Twas brillig and the slithy toves did gyre and gimble in the wabe, all mimsy were the barrowgroves, and the momewraths outgrabe…. Let’s be honest here, ok? Psychiatry is a bullshit drug racket and means of social control. It’s a PSEUDOSCIENCE!….

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