Breaking Blind: Antipsychotic Drug Efficacy May Be Overestimated

Only 4 of 188 antipsychotic trials assessed blinding, and in all 4 cases, the blind was broken, potentially leading to an overestimation of the drug effect.


A new study in BMJ Mental Health found that antipsychotic drug researchers rarely bother to assess whether they successfully blinded participants and researchers in their studies. Worse, in all four trials in which blinding was assessed—out of 188 total studies—the blind was broken.

According to the researchers, “There remains suspicion that treatment effects of antipsychotics for schizophrenia may be overestimated unless the trials are properly blinded.”

The study was led by Aran Tajika at Kyoto University Graduate School of Medicine.

The double-blind, placebo-controlled trial is the mainstay of evidence-based drug assessment. In this type of study, a drug is compared to a placebo, and neither the researcher nor the research participant knows whether the participant is receiving the drug or the placebo. If the blind is broken—meaning that the researcher or the participant (or both) have guessed whether the participant received the active drug—this can lead to overestimating the power of the drug. Researchers and participants are more likely to note an improvement if they believe the participant received the active drug.

“Blinding of randomized controlled trials (RCTs) is very important for the accurate assessment of drug efficacy. Without proper blinding, the effect of the intervention may be overestimated,” Tajika et al. write.

Just conducting a supposed “double-blind” trial is not enough, according to Tajika et al. It is also important that the blind is actually successful. One of the easiest ways to break the blind is when researchers and participants notice that they have experienced drug side effects—a big clue that they are receiving the active drug.

For this reason, it’s crucial for researchers to assess whether the blind was broken in their study. It’s easy to do so—at the end of the study, you ask the researchers and participants whether they received the drug or the placebo. If they all guess correctly, you know the blind was broken—which means the drug’s effect could be tremendously overestimated.

However, Tajika et al. note that there is no consensus on how to interpret blinding success, and the 2010 Consolidated Standards of Reporting Trials (CONSORT) statement no longer recommends that researchers test the success of their blinding process.

For antipsychotics, which have powerful sedating effects (among other harms), it can be pretty easy to tell whether you’re getting the drug or a placebo. Yet Tajika et al. observed that in trials of antipsychotic drugs for schizophrenia, the success of the blind was rarely, if ever, assessed. So, they decided to do a thorough study on this question, gathering all of the placebo-controlled trials of antipsychotics that featured a double (or more) blind.

They identified 188 such studies published between 1955 and 2021. However, only three of them had actually assessed whether the blinding process had worked—all studies of the oldest antipsychotics, chlorpromazine, haloperidol, and promazine, from the 1950s and ’60s.

After one more search, Tajika et al. found one more study from 2007 that assessed the blinding process, a drug development study of an injectable antipsychotic that is not on the market, dihydrexidine.

In all four of the studies that checked the blind, the blind was broken.

“Blinding was broken in all the four studies that we had identified. The proportion of correctly guessed allocation ranged between 70% and 91%,” they write.

It is unclear whether this has actually led to an overestimation of the effects of the drugs—the current study was not designed to examine that question. However, we do know that, in general, breaking the blind leads to an overestimation of drug effects. The researchers also note that it’s unclear to what degree the blind was actually broken in most studies.

This is particularly true for newer antipsychotic drugs, as there are no studies that assessed the blind for these, the most commonly prescribed antipsychotics today. However, it is telling that in all four studies that did assess the blind, it was broken to a significant degree.

According to Tajika et al., “Researchers should therefore be encouraged to conduct blinding assessment and report the results in each RCT. We then need to integrate the results of more studies to examine the exact rate at which blinding is broken and how they may or may not affect the effect size estimates.”

Stefan Leucht, one of the study’s co-authors, has also published research finding that only 23% of patients respond well to antipsychotic drugs, challenging the notion that these drugs are an effective treatment for psychosis.

Long-term research has found that those who used antipsychotic drugs for a more extended period had worse outcomes than those who did not—including higher rates of premature death, worse cognitive functioning, lower work functioning, and more psychotic symptoms. This was true even after accounting for baseline severity and diagnosis.




Tajika A., Furukawa, T. A., Shinohara, K., Kikuchi, S., Toyomoto, R., Furukawa, Y., . . . & Leucht, S. (2023). Blinding successfulness in antipsychotic trials of acute treatment for schizophrenia: A systematic review. BMJ Mental Health, 26(1). (Link)


  1. From: eric lawrence henry
    To: [email protected]
    Sent: Monday, 3 April 2023, 09:38:56 BST
    Subject: Council Tax Non Payment 101895977 Re. Brief History, Eric Henry, 1B Newton Rd, W2 5JP

    Dear Sir/Madam

    Brief History
    I would like to Briefly describe my History, as this is where the “SMI” comes from.

    Amsterdam 1980
    In 1980 I spent several months in Central Amsterdam (at Barndesteeg 21, 1012 BV) where I mixed socially with a Northern Irish Evangelical Christian by the name of Kevin McGrady (I believe), who went on to confess to serious crimes committed in N.I., and to support the prosecution of others.

    Kevin McGrady had been concerned about a conversation we were supposed to have had, that I couldn’t place. Shortly after this I visited a respectable restaurant; consumed a cup of coffee ; and felt very different by the time I left. Things got worse from there.

    Return to London
    When I returned to London I was arrested, my Irish Passport was confiscated, and I ended up in the UK Maudsley Hospital.

    No Reference.
    There is no reference to Amsterdam on the UK side of my Medical Records from 1980 – but there is a reference on the Irish side.

    I recovered in Ireland in the early 1980s as a result of coming off strong medications – very carefully

    Yours Sincerely

    Eric Henry

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    • It is my understanding that roughly 1/4 of people will “respond well” to any treatment, no matter how extreme or banal. For any treatment to be considered more effective than patting someone on the back and telling them they’ll get better, it should clearly show a positive outcome on at least 1/2 of the test population.

      But I totally oppose the use of drugs for the treatment of “mental illness” and pray for the day when the planet will come to its senses and realize that the mind and the brain are two completely separate things.

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  2. Antipsychotic drugs are commonly used to treat mental health conditions such as schizophrenia and bipolar disorder. They work by blocking dopamine receptors in the brain, which can help alleviate symptoms such as hallucinations and delusions. However, recent research suggests that the efficacy of these drugs may be overestimated.

    One study published in The Lancet Psychiatry analyzed data from 28 clinical trials involving over 5,000 participants. The researchers found that antipsychotic drugs were no more effective than placebo in treating symptoms of schizophrenia. In fact, participants who received placebo showed similar levels of improvement as those who received the actual drug.

    Another study published in JAMA Psychiatry analyzed data from 18 clinical trials involving over 2,500 participants. The researchers found that antipsychotic drugs were only slightly more effective than placebo in treating symptoms of bipolar disorder. However, the difference in efficacy between the drug and placebo was so small that it was unlikely to be clinically significant.

    These findings suggest that the benefits of antipsychotic drugs may be overstated, and that alternative treatments should be considered. This is especially important given the potential side effects of antipsychotic drugs, which can include weight gain, diabetes, and movement disorders.

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    • IMO the main problem is “Psychiatric Drug Withdrawal Syndrome”. When a person takes these drugs, the drugs change the brain – for the worse.

      According to Professor Harry Kennedy of the Central Mental Hospital, Ireland – his patients usually consist of people (often men) with a diagnosis of “schizophrenia”, who seriously ‘act out’ when they stop taking their ‘medication’.

      When I attempted, with permission, to come off ‘Strong Psychiatric Drugs’ abruptly, I quickly ended up in hospital. But I was ultimately able to withdraw very slowly.

      Resultant “High Anxiety” might have disabled me, only I found an “Anti Anxiety” approach that worked.

      Once I successfully stopped taking the drugs I was no longer sick and disabled.

      IMO a completely well person can be turned into a Schizophrenic through Strong Psychiatric Drug Exposure.

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  3. In college my doctor thought it was daily bipolar meds that helped me go symptom free for 18 months at a time. In hindsight it might have the mushrooms I took once that really helped. I’m not interested in trying either again but at least I’m not experiencing side effects from the mushrooms 20 years after I last used them.

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    • So many people want something they can swallow (or inject) to make them feel better!

      I hope some day it will be clear that if the mind, and not the body, is the real problem, then there is nothing you can put in your body that will make you feel better. The mind itself must be addressed.

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  4. For the industry: It’s easy and big money with little to no oversight and little to no real backlash.

    For the people who are profitted on: akathisia, anhedonia, tardive dyskinesia, gynaecomastia are some of the worst things to experience by a living being. The suicide rates with these individuals is understandable, as death becomes more healthy than the constant and brutal experiences of those things.

    It is a special kind of cruel ignorance to consistently wreck human life potential in such a way that it wrecks vast networks of lives beyond those who suffer the most, much less the environmental effects it has from the metabolites in water and soil on every part of the ecosystem.

    The existential reality of this, and its’ blatant continuance, is pushing every living thing on Earth towards desolation.

    People like myself whom are mostly decimated by decade(s) of these kinds of experiences rarely ever have functionality, much less the ability to pursue an action against such a thing for the betterment of the whole of Earth.

    May all that exists here see this and may we all realize that this is one particular movement towards desolation that can be changed quickly with accurate attention.

    Mahalo, Namaste, Ojigi, Richtig, Shalom, Shwmae Sumae, Salaam, XiĂšxie

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  5. From: eric lawrence henry
    To: Westminster Council Tax 1
    Sent: Friday, 28 April 2023, 13:55:09 BST
    Subject: Att. Sarah Lewer, Team Leader. RE: Council Tax Non Payment 101895977 (Factual Backup)

    Dear Sarah Lewer

    I mentioned on Friday 28 April 2023 telephone call (10:29 today) – that my original UK Doctor from 1980, Dr Barry Leonard Stone ‘committed suicide’ in October of 1999.

    Dr Barry Leonard Stone – BMJ Obituary
    Link (below)

    I also mentioned that the Doctor that wrote up Dr Stones obituary was banned from practising medicine within 6 months of Dr Stones death –
    Link (below)

    The Argus October 2 2001
    …and I mentioned the 1980 admitting Doctor at Galway Southern Ireland Dr F… (based in West Sussex at 2000) was also suspended within 6 months of Dr Stones Death.
    Link (below)

    “…Dr F….., who graduated in Cairo in 1972, was suspended from practising medicine in March 2000..”

    Yours Sincerely

    Eric Henry

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  6. Are there any resources available on MadinAmerica and other websites about the new drugs that are currently under development, such as Karxt or other similar types? While some of these drugs are still in the development phases, the internet suggests that they contain new and innovative ingredients. Although I may be naive, I would like to know if these upcoming antipsychotics are something that one can anticipate with optimism, especially since I am currently unable to discontinue my current antipsychotic medication without experiencing adverse effects

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    • MIA is mostly interested in looking at alternatives to the “medical model.” It is unlikely we will want to promote any “antipsychotic” drugs given the history of failure and worsening of “symptoms” and in fact the shortening of lives resulting from the “antipsychotics” currently in use. It seems very unlikely that the “new” drugs will be doing anything beyond trying to suppress dopamine and maybe suppress the uptake of Serotonin like Risperdal and Seroquel and the other current drugs.

      It is truly a problem to be unable to continue. I’m betting no one warned you this could be an outcome of taking them in the first place! Have you talked to anyone who specializes in getting off drugs? There are such people around, but most psychiatrists either don’t know or actively try to prevent any effort for people to get off.

      Anyone else have thoughts?

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  7. I believe It’s possible to overcome Anxiety with this approach

    Most of Eckhart Tolles work can be accessed on the internet free of charge.

    This book here, is somewhat similar

    Iceman Wim Hof s methods work nearly automatically
    But caution needs to be taken with any vulnerabilities

    (When a person goes into cold water the body seriously stresses. But the stress drops after a short time. And this reprogrammes the system to mostly react at a calm level).

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