How Do We Test the Effects of Long-Term Exposure to Antipsychotics?

A new attempt to study the neurological effects of long-term exposure to antipsychotics uses healthy volunteers on minimal doses for 15 days.


Although people with a schizophrenia diagnosis are often expected to take high doses of antipsychotic medications indefinitely, research on the effects of long-term exposure to antipsychotics is sparse. Now, a study claiming to investigate the effects of chronic use on the brain has started recruiting participants at McLean Hospital in Massachusetts. However, the study only lasts for 15 days and the participants will only take a minimal dose of the drug.

The recruitment information for the study suggests that the effect of long-term antipsychotic use on the brain is currently unknown. However, previous researchers have found that brain changes are associated with antipsychotic use, which the researchers acknowledge. They write that “accumulating evidence suggests that exposure to the effects of psychotropic drugs may contribute to the structural and other changes in the brain.”

Nonetheless, the researchers wanted to study whether these changes are really due to the drug. In order to do so, they propose giving antipsychotic medication (olanzapine) to “healthy volunteers” — people without a mental health diagnosis. Using healthy volunteers makes it possible to assume that any observed brain changes are due to the drug rather than the symptoms associated with the schizophrenia diagnosis.

It is unclear how a 15-day study will be able to detect brain changes that may emerge after years, or even decades, of antipsychotic use. However. the researchers state that they could not ethically give the drug to people for longer than 15 days, as this is “the longest but historically safe olanzapine usage period in healthy individuals up to now.”

Additionally, although the recommended daily dosage (according to the American Psychiatric Association guidelines) is up to 30 mg of olanzapine, the researchers plan to give the participants only 5 mg of olanzapine a day. They state that this is to “protect the participants from adverse effects of treatment.”

The researchers expressly acknowledge that the recommended dose is unsafe and that it would be unethical to expose their subjects to the effects of the medication.

If the researchers do not detect any significant brain changes after 15 days, the results may be used to suggest that olanzapine has little to no effect on brain metabolism. They write: “A not-statistically significant finding with this sample size will suggest that any effects of olanzapine on brain metabolism are small at most.”

The researchers don’t say whether a larger dose, or a longer period of administration — something more akin to how the drug is prescribed in the real world — might have a larger effect on the brain.

Known adverse effects of antipsychotic drugs include parkinsonism, weight gain, metabolic problems, diabetes, cognitive decline, and akathisia, an intense inner agitation that’s been correlated with suicidal thoughts.

The drugs are also known to cause dopamine supersensitivity, which may lead to a relapse of psychotic symptoms. A number of studies have demonstrated lower relapse rates for people who did not take antipsychotics long-term.


**** Identifier: NCT02536846

Link to Study:

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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. Who is going to agree to this? How much will they have to pay study participants to get them to comply? And how many will drop out before the 15 days are up?

    Olanzapine has been out for about 20 years now. So now they’re doing this study? So now they suspect the drug damages people?

    They won’t find much. They don’t dare keep normal human beings on the stuff any longer than 15 days. What about us? We’re not human. We don’t count.

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    • You’re right.

      The “severely mentally ill” are supposed to be subhuman and dangerous. So it’s okay to perform cruel, pointless experiments since they say our brains are already broken and we’re only fit for institutions anyhow. (According to Jaffe in a Youtube video I saw.)

      In the sight of God those like him may be far less worthy of life than the “defectives” whom they judge fit only to be crippled or killed and tossed into the dust heap. 🙁

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  2. “The researchers expressly acknowledge that the recommended dose is unsafe and that it would be unethical to expose their subjects to the effects of the medication.”

    This statement says it all. It’s okay (i.e. “ethical”) to damage crazies, but as for “normal” people, not if they, the researchers, can help it. I’d call that just one double standard among many.

    Great article. It should be interesting to see how much brain structure might change on a weeks dose of 5 milligrams of Olanzapine a day. I’d think it might be more difficult to do the same experiment if your drug was Thorazine or Haldol, the drug they test drugs like Olanzapine against.

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      • Why indeed–assuming our brains were deformed–would they subject it to drugs that damage already healthy brains? Some use the chemotherapy analogy. But you have to prove the cancer exists first and it’s acknowledged to be a desperate remedy not to be performed indefinitely over 20-30 years.

        However, this makes sense when you realize psychiatry is not about saving lives, healing brains nor helping people lead higher quality lives.

        It’s really about segregating and crippling the “unfit.” Barring us from participating in the marketplace–which is linked to eugenics according to an article I read. And preventing us from reproducing since the drugs render us grotesque to behold and often cause impotence/frigidity.

        They pretend their victims are dangerous in order to justify crippling them. Not about health or independence/ but creating docility, helplessness, and stupidity. Psychiatry’s real function.

        Thieves who only break in to steal and kill.

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    • It might be interesting to see how many “normal” people suffer a first episode psychosis within 15 days, even on that low dose of Zyprexa. I know it took about that long for me to suffer from my first ever episode of psychosis on a child’s dose of Risperdal, although it was given to cover up the common symptoms of antidepressant discontinuation syndrome.

      And both the antidepressants and antipsychotics are anticholinergic drugs, both are known to create psychosis, via anticholinergic toxidrome. But I was a “normal” person, prior to being defamed with a “metaphorical ‘illness of the brain.'” And I still am a normal person, now that I’ve been off the psych drugs a long time. Some “hey, you ‘mental health’ researchers are morally repugnant” should be made “out of that admission.”

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  3. I need to create a fake name, fake situation…Oh, an acting job! Well weren’t my 35 years as a mental patient the greatest acting job of my life? I loved the staff, of course I did, thought they were the greatest and said, most dutifully, that getting locked up was okay because I deserved it.

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  4. Thank you very much for spreading this information on this website. It is very useful for me.
    I personally decided to stop all psych drugs by myself as the psychiatrist said I can never heal and will need them for the rest of my life. I researched by myself a safe way to do it and I believe I made the right decision.
    No relapses of the problem that leaded me to being medicated at all and luckily, side effects from medications stopped some time after I quit.
    Still, I have a friend who is being permanently drugged and feels benefited from the treatment. She had very serious problems that put her life in danger (some of the most dangerous thoughts and behaviours that I have ever heard) so I don’t even risk to interfere by showing her this kind of information and even though I personally think that as long as she believes that she is sick and there is no way she will never get better, she finds meds are the safest she can do.
    She even says: since I don’t have a healthy brain, thank God for olanzapine, If I lived in the past I would be going through lobotomy. So she accepts and believes in the whole psychiatry speech and feels benefited by it, even though meds didn’t stop her from hearing voices that told her to break the mirror and cut her own throat. She almost killed herself on that day and it’s very serious.
    Her former doctor said when this kind of thing happens she should take a second antipsychotic and that is what she did. She fainted and had to be hospitalized because of it and the second doctor said taking so much antipsychotics like that was actually very dangerous. What to do?
    I believe in my recovery and it’s working, my life is better without drugs and I think one of the biggest problems in psychiatry is dividing groups of people with similar behaviours to give a same diagnose and drug treatment with no “brain abnormality” scientific evidation, so how to help someone like her case?
    Any safe helpful advise, even if it is just a complement to lifelong drugging, which she will probably do?

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  5. Gee, Mr, Simon..according to the industry’s own ‘experts’, here I am….long-term use by someone who wasn’t ‘mentally ill’….”life’long”.bipolar 1 to “oops, never mind, good bye & good luck”……according to the ‘diagnostic’, party-line, paperwork.

    11 years of chemically-initiated ‘Parkinsonian’ effects AND NMS-created paralysis (twice), glucose spikes, kidney function drops, liver toxicity, hospitalized akathisia and anorexia, brain lesions, 85-lb weight gain=joint erosion=cortisone treatment, irrational fears and GAD, acute depression, suicidal ideation, drooling AND damaged salivary glands, facial tardive dyskenisia, club-footed gait, fingernail-splitting, ‘stress’-eczema, hair loss, anosognosia, gulping for air, vertigo, and hospitalized bradycardia.

    After withdrawing for 2+ years…. I’ve ONLY had 16 ‘partial-seizures’ that have ‘mystified’ my GP, the ER, my cardiologist, my neurologist, and Barrow Neurological Institute/Phoenix…..because no one is ‘comfortable or conversant’ with psych drug effects or prognosis and my insurance won’t cover the ‘2nd-tier’ testing it would take and specialists it requires to interpret them. They don’t read the Andreason report I carry ‘with’ to all appointments. Apparently my credibility is ALSO still damaged by the false diagnosis….forever, indelibly stained by Seroquel, Risperdal, Geodon, et al.

    But I know….

    On the way out the door, I’m invariably told quietly, quasi-conspiratorially… “We’re seeing a lot more of “this””.

    Gee, THAT’S comforting.

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    • If it makes you feel better Krista the massive damage in psychiatry’s wake is restoring your credibility.

      Many KNOW you are telling the truth but feign skepticism or disbelief. Afraid of betraying the Brotherhood I guess. This going along with whatever psychiatrists say though they know it’s harming people and not helping will kill Western Medicine.

      All the evil “doctors” need is for the good doctors to do nothing.

      Have you heard of Farid Fata the cancer doctor who deliberately misdiagnosed healthy people with leukemia to sell endless rounds of chemo? Killing some and crippling others? Other doctors knew. But it took a long time till one finally blew the whistle.

      Scary how morally bankrupt the medical profession is now.

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  6. Hey Rachel, Thx for your kind words on this thread.
    Credibility is the most significant concept in my history; the stripping of it at diagnosis and the deathmatch to restore it. The irony that it still eludes me with some doctors has left me upset AND bemused.

    During an ER-side-effect ‘visit’, a YOUNG doc really believed me and expressed cynical alarm about my condition. It was nice but…then the next day he called me at home with the name of a “good” psychiatrist.
    Bless his heart…really.
    #1) While the psych was listed in my Provider Directory, when I called they were amused and annoyed, as he was a ‘Phantom Network’ listing by Magellan (BH management industry leader), falsifying the number of physician choices to ‘pad’ their bid to the state, ultimately winning the 2 Billion dollar contract AGAIN (#1 or #2 largest at the time). Milo Geyelin/Wall Street Journal uncovered this massively profitable scam and how it harms body and spirit of clients in BH state care/Medicaid.
    In my desperation for options and better services I called 40 offices. Disconnected phones, hospital reception desks, and doctor offices laughing at me were the response for ALL 40.
    Sometimes other states’ legislators fine them lunch money ($250,000 or so) which is just the cost of doing business for them….but they don’t interfere as ‘mentally ill’ citizens aren’t a voting block of influence.

    #2) Another YOUNG ER doc believed me and spent a long time listening to me and my situation, allowing me to dictate to HIM what tiny amount (1 mg) of diazepam would assuage my panic (heart palps) during withdrawal, but not add to my pollution and interfere with my forward progress off EVERYTHING.

    While fighting my way out, I had to McGuyver every appointment while under internal/external siege from the drugs, especially with an unknown doc, sussing them out quickly to determine what approach would PSYCHOLOGICALLY (irony, anybody?) appeal to their sense of professionalism, ethics/ego, and scant knowledge of the psychiatric industry (a given) to achieve what I needed, without ONE STEP backward. I learned to stop trying to ‘recruit’ them to my side and focus on my input to be considered and acted upon. Many were relieved to be ‘absolved’ of responsibility as psychiatry ‘issues’ with meds scares the pants off most of them (liability).

    It was a stress and exhaustion factor of 11..on the ‘Spinal Tap’ scale.
    There was not one second of just unclenching and trusting someone to help me.

    I’ve mentioned it before; I didn’t now where my stamina came from (lizard-brain, ice-cold, ‘controlled’ rage) considering the damages.

    It could have gone the other way…I’d still be in there, in a chair, staring out a window in my adult diaper.

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    • Krista, spot on……”PSYCHOLOGY” (irony anyone?) I think of all the ones that do not know, did not know. Psychiatry is such an embarrassment in a society that is trying to move forward. They exist because we are too busy to notice, too busy to stand up for Dick and Jane. Psychiatry laughs at insight, but it is a maniacal, defensive laughter. It is a wait and see on who has the last laugh. I believe the more psychiatry recruits, the more it will backfire. Recruiting more and more is NOT a sign of permanency.

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    • Don, that’s why I want to sign up as fake patient. Just to get the inside dirt.

      My guess is they’ll keep it on the market. We don’t matter. Mostly, we’re out of work and expensive for taxpayers. Of course, psych caused this, but anyway I am sure they won’t change anything at all. They want to keep us this way, silenced and marginalized.

      I took Olanzapine and had to stop it after three days. This was back in 1997. It was intolerable.

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  7. Krista, it never occurred to me when I was back in Massachusetts that the Medicaid listings were faked. I didn’t have a grasp on how the funding worked. I made roughly 200 calls trying to find a therapist after I had fired the abusive one I had. I found that the Medicaid list was totally useless and after I exhausted that, I called at random. The National Eating Disorders Association was also unhelpful, as both the local and national chapters failed to locate even one therapist who took both ‘care and ‘caid. I lived in Boston and all 200 turned me down before I got into the door. I was suffering from severe trauma from the abuse. I kept trying and trying and I remember hanging up the phone after one failed call after another and just crying. I had my lovely dog. I had no one else, and my supposed “friends” thought the abuse was my imagination.

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  8. Hey Julie, Phantom Networking is a real ‘thing’; cynical, corrupt, and ‘who gives a sh*t’. My ‘exit’ doctor had no idea and was very uncomfortable with the article(s) I tossed on his desk. I took him by surprise. I didn’t expect him to apologize or ‘whatever’… I knew he didn’t know, he had never SEEN the Provider Directory.
    And we moved on, but I had quietly, politely established my credibility and strength in ‘I’m two steps ahead of you, I know what all this means now…I understand what has happened’. We didn’t waste time talking about it much…I was wholly in the present.
    When I started to research the sordid facts and ‘big picture’ of ‘How Psychiatry Works, Really’ … the lightbulb went on like a nuke.
    My outrage and shock was met by family and friends unable to meet my eyes; they were uncomfortable with what sounded like ‘off-the-rails’ paranoia, tin-foil-hat-conspiracies by someone who was, as my compassionate R.N. brother said, “circling the drain”.
    I abruptly cut them ALL out of MY life as I was now FULLY engaged and had no time for distractions and cheap sentiment, fighting something they couldn’t understand and didn’t love me enough to try. F*%# em’. I wasn’t mad, they were superfluous.

    It was me and my concerned cat. And no one else for 2 years. I made pre-emptory measures for her in case I failed and was institutionalized…very organized, calm, and bizarre…. had this been different circumstances.

    The day I walked out of there with the ‘exonerating’ paperwork, almost finished withdrawing…and alive…I stopped at the Dairy Queen for the LARGE Cookie Dough Blizzard and went home to her. There was no one else to cheer for me on the most significant day of my life. Eh…I was going to be fine cause this was the worst of life and I had won.

    Almost 4 years later, I’m better than I ever was. I was living a charmed life compared to what I didn’t know was coming at 54 years old in 2004. It changed me (how could it not?) and I imagine who I would have been without this pain and salvation… without this ‘test’.

    This is better…and I haven’t had an ‘event’ in 7 months.
    The future is bright. I wish that for you, too.

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  9. Since they are using healthy volunteers, why exactly are psychiatrist or doctors not participating as the volunteers? 15 days of the lowest dose should really not hurt that much dear doctor. Ok doc, or researcher, you go first, come now, don’t be paranoid of the ‘side effects’. Or perhaps you get your kicks in another way. Oye, the insanity of it all. Did they all enter a state of something long ago and simply stayed that way and have become to have grandiose views as having some kind of solution to a problem? I can counsel them on grandiose views and entrenched beliefs. Debriefing is painless. Of course they will not submit to me, least I can do is spread the opposite gospel… yes, I saw my neighbour lose his brain from pills. Well done psychiatry. But you might say that I have no scientific evidence that it was meds. Honestly get some help or leave the profession. You are an embarrassment all around. I can’t imagine to have anyone of these yahoos as my son in law. My kids are too special and educated (and scared of me, lol) to ever bring anyone so narrow minded home to mom. In our house we discuss the pros and cons of systems, and we believe that we would give psychiatry the benefit of the doubt if they had a shred of decency, and knew how to admit failure, knew their own obsessions and biases.

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  10. ” However. the researchers state that they could not ethically give the drug to people for longer than 15 days, as this is “the longest but historically safe olanzapine usage period in healthy individuals up to now.”
    Additionally, although the recommended daily dosage (according to the American Psychiatric Association guidelines) is up to 30 mg of olanzapine, the researchers plan to give the participants only 5 mg of olanzapine a day”

    Who recommends a study like this without it looking laughable to even the most unaware about the machine?
    This attempt proves how stupid psychiatry and drugsters believes the public is, and perhaps they have a point. Doing studies like this is just to check how much they can get away with…it is a way of checking billions of people’s intelligence or common sense levels, or if they care at all.

    They obviously expect people to point out it’s ridiculous plan.

    It is like giving healthy volunteers 2-4 drinks per day for 15 days and proving that no liver or other damage happened, so a large amount of alcohol consumption would be okay over 20 years.

    But arguing the study is what they want, instead of the laughter it should receive.

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