A Recent Study of Atypical Neuroleptics: “The Results of our Study are Sobering”


This week, MIA highlighted a recently published study of the four most commonly prescribed neurolpetics.  As noted in the post, the major outcome was that these drugs were not found to be effective or safe.

This important study, co-authored by Dilip Jeste the current president of the American Psychiatric Association, is worth reviewing in greater detail.

The study was modeled to capture clinical practice.  Entry to the study was broad and not limited to a specific diagnostic category.  It is characterized as a study of “older adults” and I admit to some chagrin that this meant anyone over 40.  Diagnoses included schizophrenia, schizoaffective disorder,  and psychosis associated with mood disorder, PTSD or dementia.  It was open to individuals who were either already taking an atypical neuroleptic or had a psychiatrist who was recommending this.

Individuals were admitted to the study if they were willing to be randomized to at least 2 of the drugs studied: olanzapine, risperidone, aripiprazole, or quetiapine.   So a person who was only willing to take, for example, olanzapine and aripiprazole, for example could be included but a person who was only willing to take risperidone could not. These four drugs were selected because they are the most commonly prescribed atypical neuroleptics. Subjects were then assigned to one of the drugs using a technique called equipoise-stratified randomization. Each subject had a list of acceptable drugs and was then randomized to one of the drugs along with all others who had an identical list.

Assessment was single blinded; subjects and their treating physicians knew which drug they were taking but the raters did not.  Ratings were done at baseline and periodically over 2 years.  They were assessed on a variety of measures including time to discontinuation of initial drug, Brief Psychiatric Rating Scale (BPRS) and its psychosis subscale, drug side effects, and metabolic parameters.  A total of 332 individuals consented to the study and completed at least a baseline visit.

The primary outcome – similar to what was used in the CATIE study – was time to discontinuation of the first drug used.  The percentage of patients who stopped the first drug used ranged from 78.6% for quetiapine to 81.5% for aripiprazole.  The average time until discontinuation was 26 weeks. Most people who stopped the first drug were started on another one so early discontinuation does not appear to be secondary to remission of symptoms. Reasons stated for discontinuation included side effects (51.6%) and  lack of effectiveness (26.9%).

What was most striking to me is this line from the study: there was

“no significant change in psychopathology with any of the study atypical antipsychotics

They did not even report the numbers in their report.  (Note: they did report baseline BPRS total score.  Across all groups the mean (and standard deviation) was 40.1 (10.3). This corresponds to a person who would be considered moderately ill according to at least one report.)

Also of note, they discontinued the use of quetiapine after 3.5 years due to a high incidence of adverse side effects.

The one year incidence of metabolic syndrome was 36.5%.

The authors discussion is so compelling, rather than paraphrasing, I will just quote directly:

“the results of our study are sobering.”

“there was no significant improvement in BPRS total or psychosis subscale scores over a 6 month period.”

“the overall risk-benefit ratio for the atypical antipsychotics in patients over age 40 was not favorable, irrespective of diagnosis and drug.”

And finally,

“Shared decision making, involving detailed discussions with the patients and their family members or legal guardians about the risks and benefits of atypical antipsychotics and possible treatment alternatives, as well as of no pharmacologic treatment is warranted.” (bolding mine).


We often discuss the serious side effects of these drugs in the context of their presumptive benefit. To reiterate, unless I missed something,  in this study they did not find any benefit.

I want to give a nod to 1boringoldman for also alerting me to this study. His comments on this and many other topics are worth reading.

I wrote previously about another large a study that suggested that these drugs have relatively weak effects.  I am curious to see what the impact of these studies is on accepted practice within psychiatry.  Yesterday, the APA Board of trustees voted to approve the new DSM-5. This will undoubtedly gain significant attention within and outside of our field.  The time and expense that will be devoted to the role out of this edition is enormous. From my vantage point, it seems more important to put our energies into a serious consideration of the impacts and efficacy of the treatments we so readily prescribe than to a diagnostic manual that has so many problems.


Mad in America hosts blogs by a diverse group of writers. These posts are designed to serve as a public forum for a discussion—broadly speaking—of psychiatry and its treatments. The opinions expressed are the writers’ own.


  1. I think that the press play an important part in how psychiatric treatment develops. Mr Whittaker point this out in Anatomy of an Epidemic. So it maybe that DSM gets lots of press coverage and this article gets almost none.

    It would be great if someone could get this article some mainstream press attention.

  2. Do you know where we are right now? Where tobacco was after the surgeon general’s report that it causes cancer. Everyone knows there is a problem. Very few know there is a solution.

    What was the solution for tobacco? Raising cigarette taxes so that tobacco companies couldn’t externalize the cost of their pollution as much. Same solution as for stopping big oil, big agra, etc. Add up all the toll of a psych med.

    The $20 billion in settlements so far was just money paid to medicaid. They also need to pay for the cost of early deaths, lost time in the labor force, disfiguration, cognitive damage, our ability to have children and spouses, many of us. They need to pay for all that. And then they’ll be done, and they have won. Because cigarettes keep selling because of illegal developing world marketing, but also because it feels good to smoke. But very little about psych meds ever feels good.

    So sorry if Tina Minkowitz already wrote all this in her reparations post. I haven’t read that one yet.

  3. Sandra

    You said above “I do give the authors credit for not trying to spin the data.”

    Think about the implications of this statement. Think about how low our expectations of truth and honesty has fallen when it comes to Biological Psychiatry. These are suppose to be scientists and doctors who have promised to “do no harm” and be dedicated to upholding the truth no matter what the data tells us. Human lives as well as the health of their brains are on the line here.

    Can you image if these results came out about a heart medication or a diabetes medication, do you think the final sentence of a study would have been that doctors need to exercise “caution” in their prescribing?

    In this case atypical anti-psychotic medications are so intimately bound up in the “raison d’etre” for these doctors that they can’t put ethics and the well being of their patients over their investment in Biological Psychiatry as a model of treatment.

    Sandra, this is exactly why some of us on MIA are not “anti-psychiatry” but “anti-Biological Psychiatry” and you should be too. I appreciate your participation here and I hope you play a role in challenging this model of treatment within your field; it needs to be defeated and dismantled.


    • Dear Richard,

      What do you think about”How A Bone Disease Grew To Fit The Prescription”?

      (…) Osteopenia is a condition that only recently started to be thought of as a problem that required treatment. Until the early 1990s, only a handful of people had even heard the word. And to understand how osteopenia was transformed from a rarely heard word into a problem that millions of women swallow pills to treat, you need to go back to the beginning; (…)
      For a long time doctors and researchers were only able to diagnose osteoporosis after a woman experienced a bone fracture. But by the early ’90s technology had evolved, and bone scanners made it possible to determine whether the bones were weak before any fractures occurred.

      The question before the experts in Rome then was this: Since after the age of 30 all bones lose density, how much bone loss was normal? And, how much put women at risk and therefore should be considered a disease?

      (…)”Ultimately it was just a matter of, ‘Well … it has to be drawn somewhere,’ ” Tosteson says. “And as I recall, it was very hot in the meeting room, and people were in shirt sleeves and, you know, it was time to kind of move on, if you will. And, I can’t quite frankly remember who it was who stood up and drew the picture and said, ‘Well, let’s just do this.’ ”

      So there in the hotel room someone literally stood up, drew a line through a graph depicting diminishing bone density and decreed: Every woman on one side of this line has a disease.

      Then a new question arose: How do you categorize the women who are just on the other side of that line?

      To address this issue, Tosteson says, the experts — more or less off the cuff — decided to use the term osteopenia. Tosteson says they created the category mostly because they thought it might be useful for public health researchers who like clear categories for their studies. They never imagined, she says, that people would come to think of osteopenia as a disease in itself to be treated. The chairman of the meeting, John Kanis, of the WHO Collaborating Centre for Metabolic Bone Diseases, says the same thing.

      Nevertheless, 17 years later Banghauser, of Richmond, Va., a woman whose bone density is just a hair away from that of the average healthy 30-year old, is not only medicated for osteopenia but literally spends her days worried about breaking a bone.

      “I used to run marathons, and I would fall and trip on broken sidewalks,” she told me. “And you know initially before I had this diagnosis I didn’t think anything of it. But now every time I fall I get up and think, ‘Oh, good, I haven’t broken anything.’ ”

      “I’m much more aware of making sure I lift my feet up and I don’t trip on the sidewalks, but you know, if I didn’t know that I had osteopenia, maybe I wouldn’t be so cautious.”

      So how did osteopenia change from a category for public health researchers into a condition that millions of women swallow pills to treat?

      The answer to that question starts with a man named Jeremy Allen, who lives in a sprawling home in Pennsylvania (…).


  4. This study sounds familiar, except that the same sort of thing was done in the early psychosis program that my son was enrolled in for two years. I reached the same conclusions as Dilip Jeste – amazing – and I haven’t even got an M.D. or a Ph.D. Patients don’t have time for a bunch of academics to get their act together. The program my son attended insisted that everybody take not one, but two drugs in what the doctors considered “low doses,” because two drugs at low doses were considered more effective than one. Metabolic weight gain? Of course. Discontinuation of one drug and then substituting a new one because the patient wasn’t improving was the norm. But, much as I insisted that one ineffective drug would do (since two ineffective drugs seemed like overkill), I was merely a bystander. So, I don’t really get what all the fuss is about with this latest study. It doesn’t matter what drugs were studied, they would get more or less the same results with others.

  5. Duane,

    ///In the case of psychiatric treatment, it seems quite obvious that the field cannot point to *life-saving* treatment, considering the drugs cause more harm than good, increase suicide rates, and injure the brain, body, mind.///

    I feel that,on the general population level, psychiatric drugs might do more harm than good but I really don’t know because some people want pills and a quick -fix and may be would use more street drugs to get relief or put themselves into dangerous gourou hands- you do not seem to be one to me but those people do exist.

    Actually, what I have been doing since 1989 has been to try and help on a pro bono basis some people escaping escapable psychiatric drugs and psychiatric labels using a gynacologist hormonal prescription sometimes, psychotherapy, support and education about diet and about sleep among other things , homeopathy, exercise you name it.

    I found, in particular, ludicrous that the DSM5 will consider acute grief not contradictory with a diagnostic of major depression (and even more that they would suppress Asperger’s syndrome from the American classification).

    Also, cheap estrogen (plus progesterone for the women still having their uterus) hormonal therapy should be considered so dangerous when many women -and the more so when they are autistic- get a bipolar diagnosis and more dangerous treatment like neuroleptics.

    Still, I always told some people to go and see a colleague psychiatrist prescribing allopathic drugs because my experience is that some people benefit greatly from psychiatric drugs.

    I also believe that some premature deaths by suicide can be prevented by ECT as I already wrote on Pr Healy’s blog.

    Ignoring that a very severely depressed mother or father can kill herself and her children (“altruistic suicide” is this called in French) is just unpreofessional for somebody working in health care and I am sure you know that.

    NB: I am not saying that antidepressant or ECT are the solution her: hormonal treatment or social housing or legal support against an abusing spouse can be the solution.

    As I already mentioned on Corinna ‘s blog that a French psychiatrist has been put to trial in Marseilles for not having prescribed neuroleptics in a depot form and not having kept in the hospital a man with a history of violence and of stopping his medication who stopped one more time his neuroleptic treatment and killed his mother’s partner. And that colleague had non only tried to hospitalize the man when he came as an outpatient to consult her but she had taken the difficult ethical step to call the mother telling her son was dangerous to her partner and the police as well in order to have the client safe at a hospital.

    As disgusted as I was (and still am) with the paternalism of French psychiatrists in general when I took on pro bono work for people not in need of a psychiatric label and treatment in 1989 and as disgusted I was (and still am) in 1986 with the psychiatrist academics ‘s manner to conduct ” silly monoaminerhgic simplistic or dishonest on bad pharma payroll biological psychiatry researches” -with the only exception of epidemiologists-

    I find just not acceptable to pretend that nobody can ever be helped by psychiatric drugs and forced hospitalization and even ECT in desperate cases and that anybody can be helped by peer support or professionals like yourself.

    I find recovery a nice aim but a dead person cannot recover. Can she?

    To provide availability for peer support and professionnal like yourself is a good and fine thing but you are not going to make it mandatory and send the police to people’s homes because they do not want to use your services or Corinna’s. Or are you?

    (Some non-psychiatrists healers can be as paternalistic as your average French psychiatrist -not that you seem to be one to me.)

    • No, I’m hardly “paternalistic”.
      In fact, I have some strong libertarian tendencies – adults should be allowed to make their own decisions.

      Unfortunately, when it comes to psychiatric treatment we do not have *fully-informed* consent. We are not even close!

      And, people are not told of *options* – non-drug, safe and effective options.


      • Hi Duane,

        ///adults should be allowed to make their own decisions.///

        How right could you be Duane!

        And I would add that adults should be allowed to make their own decision for their children but should never be allowed to make decisions for elderly parents able to consent no matter how poor or frail those parents can be.

        Taking psychiatric drugs or having ECT are just that to my mind: an option and not one I recommend myself if I see another possibility.

        I cannot think that activists denying to anyone in any circonstance the right to ask for psychiatric drugs -or even to agree to ECT in desperate cases are pro freedom.

        For example, I heard an autistic advocate doing a PhD and raising children telling that risperidone had been a great help during a discussion at a meeting organized by autistic persons for autistic persons were I felt privileged to have been invited last summer in GB (AUTSCAPE).

        Who I am and who are you to tell that intelligent person wrong?

        Some elderly people risk to lose living in their own home or in a pleasant retirement home when they are too vocal and energetic about some persecutory ideas they have got from voices in their head. When everything else has failed it might be difficult not to propose a few drops of haloperidol to get the person free of the voices to see if it works and what are the side-effects…

        Other elderly people want to drink coffee all day long and after diner, watch TV a lot instead of taking fresh air and exercise during the day and watch TV at night in their beds, eat heavy diner and take psychiatric drugs to sleep when benzodiazepines are very dangerous…

        A very vocal ECT opponent and innovative thinker for sure about “labeling” , a psychologist, Pr. David Bentall who wants for GB psychologists the right to prescribe dangerous psychiatric drugs without any medical training wrote in one of his books that nothing could have saved a client of his who hanged himself in the middle of a divorce on the evening his children were celebrating Christmas with his estranged wife- after having trying to hang himself shortly before he succeeded at it.For myself, I think mandatory hospitalization for the time beings until the end of the divorce procedure or ECT should have been proposed to the man after he first tried to hang himself around Christmas which is often a very difficult time for those without a family in good shape.

        2) Every society has to draw a line between individual freedom and safety of the population at large (or the children’s safety when parental authority is concerned).

        Sadly, in France the former president, Nicolas Sarkosy, pushed strongly for insuring the safety of the population at large against the rights of the mentally ills each and every time a violent crime by a mentally ill person was in the news and many people do not believe in France that the justice system is independent enough from the government…
        ( I must write on their behalf that the French psychiatrists – as paternalistic as they can be from an Italian point of view, so to speak- are on the whole fighting against that move but they lost with the public opinion.)

        It might be different in the USA because you have better journalists and better organized activists but even in a free country of your reality or of your dreams, the line has to be drawn somewhere.

        As I have already written to Corinna, I am sure that –law and judges permitting it – many psychiatrists in many countries will be more than happy to leave yourself or Corinna West the responsibility to look after in a caring and healing of any very delusional person who told his psychiatrist how urgent it is for his step father to be dead…

        Nice to have had a dialogue with you.
        I wish you a nice holiday seasons and a happy new year 2013 Duane.


        • Dear Ivana

          you seem to be confusing several issues here:

          1 the dangers of non-medical practitioners who offer treatments to mentally distressed people such. Sometimes they are called Quacks. In another post you mentioned Scientologists and some would consider them to be one type of Quack

          2 the issue of freedom of choice, ie should patients be allowed to make informed choices about treatments and how much influence should Dr’s have in making these decisions?

          3 under what guidelines should Dr’s prescribe certain treatments. How reliable are the current guidelines? Who develops these guidelines and why?

          4 what are the best proven treatments for people showing extreme mental distress? How do these compare to current popular treatments?

          5 medical conditions and medical drugs that produce mood disturbances and psychosis which then often gets treated by psychiatrists. Something which I am sure does happen, and indeed happened to a friend of mine, but which is not the majority of cases.

          6 the morality of forced treatments in cases of extreme mental distress.

          I find it all rather confusing. I am not sure if all of these points are raised by the original post, in this case by Sandra. Although I could answer all of the points you raise (because I like to exercise my mind and show I can use it think sometimes) once I had thought about what you were raising and how the examples you raise point to various issues it would be a lot of hard work think it all through.

          You obviously want to debate these issues but I’m not sure this is the right forum for you to get all your questions answered to your satisfaction

          • Hi John,

            My brocken English must be at fault there, John, since you didn’t understand that I was answering Richard’s and Duane’s comments.

            I hope that my conversing with Duane from Texas, Richard and Stephen gives me more satisfaction than my answers to them grieve you.

  6. Sandy, thank you for bringing us the news of this important study.

    This is a mainstream study. It’s big, with over 300 participants, and one of the authors is Dilip Jeste, the current president of the American Psychiatric Association. Nobody could claim that it was somehow fringe science.

    I think this is good for my legal practice, but there are questions that I’m not clear on how they fit in with what we do.

    First, I’m not sure about dosages. For instance in Risperidone, the drug I’m most familiar with dosing of, the mean dose was 1.8 milligrams, which is considerably lower than what they give most of our clients. It’s unclear whether a higher dose would have led to better results, although it’s worth noting that the treating docs were allowed to raise the dose as part of the study; I think we can infer from this that anyone who thought a higher dose was needed administered a higher dose.

    Second, it appears that the study participants were all or primarily outpatients, which would leave the door open for the state to argue that someone requiring an emergency inpatient admission can be distinguished from the participants of this study. This might also play into the discussion of dosing.

    Third, while the study finds essentially no benefits from the drugs, I don’t read it to say anything about the course of the subjects’ condition after meds were discontinued, which would be useful for cases involving continued treatment.

    We’ve reached the point where almost every week there’s a new revelation of the shortcomings of psychiatric drugs and practices. Any psychiatrist, particularly in the involuntary system, who is not seriously reevaluating his or her practices is seriously neglecting his or her professional and moral responsibilities.

    • Any time that a patient in the state hospital where I work refuses to take the toxic drugs, which is their only treatment, the psychiatrists threaten to take them to court and have them committed for another 45-180 days. They are certainly not reevaluating anything at this point, other than their power to coerce people into doing what they want them to do. I agree with you that they better start doing so because who know, eventually there may be lawsuits brought against numerous psychiatrists for the lack of proper treatment.

      • I Stephen,

        To look on the bright side, that study will come to the rescue of any psychiatrist not keen on prescribing those neuroleptics to any elderly person – be it because that psychiatrist thinks that cheap haloperidol works better often on the voices and smelling of poison of the elderly and not everybody gets marked neurological adverse effects from it or because that psychiatrist doesn’t want to prescribe any neuroleptics at all to the client if he can help it.

        Always nice to discuss things with you Stephen since you are open to dialogue and you do not defend the same fixed views times and times again and you have interesting experience to share. I would recommend everyone to read your full discussion with Alice Keys including your fond memory of the family doctor of your childhood and I am glad you wrote to Alice Keys, among other things of the utmost interest:

        ///One of the things I’ve decided is that it’s not only the biopsychiatrists, or psychiatrists in general, that have to answer some difficult questions and be held to accountability.///


        You often write about the experience of someone working in a USA psychiatric hospital but not as a psychiatrist and some thing is fascinating to me about it:
        only psychiatrists seem to behave badly in the hospital where you work!

        I think, Stephen , that the USA America really is God chosen country if you are blessed there with only psychiatrists being to blame and nurses and support staff wonderfully dedicated to their task!

        To be absolutely frank, Stephen, although it was not my main reason to stop working in the psychiatry hospital care in 1989, some of the French nursing staff and support workers in psychiatry were very problematic to work with for me:

        Most nurses had a great sense of duty and were very humane and pleased to work in psychiatryand I learned more from some of them: a good nurse observation had even lead me to my research subject.

        That kind of attitude might not exist where you work or in the USA at large but, for example, I met more than once in France with some nurses and support workers who would say “the schizo in room X “ or “ the depression in room Y “instead of a name after the client had been hospitalized for some times with the numerous occasion a nurse or a support worker has to check and write the patients’ names. It was not unusual then and it is still frequent in France nowadays to hear the non doctor staff speak meanly of the family. To tell you a true story, once a social worker refused to do her job when I asked her about finding financial and humane support for a family telling me that first she had her children who where on school holiday and she had to be home a lot and second, since it was the mother’s fault if the son was “a schizo”, money struggling single mother or not, that woman could keep him at her home without help and at her expenses and not the taxpayer ‘s for as long as possible!

        To come back to neuroleptic prescroption, some psychiatric nurses and nurses helpers put their safety and comforts first and were making light of the drugs side-effects: It was so easy for nurses wanting a good nap on a chair or to play cards with colleagues at night – to blackmail the psychiatrist on call into overprescribing dangerous drugs for a new client or even into prescribing physical restraint with the argument that the nursing staff or another patient will be physically hurt in the next hours of the night by the emergency patient..A French TV documentary in 2010 has shown me an even worst king of nurse ‘s behavior with a nurse coming into an argument with a young woman asking to go in the garden and smoke with some warm clothes under her psychiatric in-client thin pajamas and a man nurse answering in a very vulgar way that either she had to froze if she wanted to smoke. The young woman protested and got vocal and ended up under physical restraints with a neuroleptic injection in her bottom decided by the woman nurse who came to the rescue and explaining to the man that the client was in a dissociative state and, believe it or not, the reporters and cameras presence where known to the nurses…

        Luckily, I can put here a link in English about support staff being involved in incredibly sadistic criminal attitudes against vulnerable people.
        // (…)Last week six people were jailed for their role in abusing patients at the private hospital near Bristol after an investigation by BBC’s Panorama.
        “What has been exposed by Panorama is utterly intolerable and has to come to an end,” Mr Lamb told the Commons. (…)///
        ///(…) A BBC Panorama programme last year showed footage of patients being wrestled to the floor to be restrained, the use of water-based punishment and unequal games of strength which the patients could not possibly win.
        An undercover reporter managed to get a job as a support worker and filmed colleagues tormenting, bullying and assaulting patients during five weeks at the hospital last year.
        He was sent in after the owners, Castlebeck Ltd, and the Care Quality Commission failed to respond to disclosures by a whistleblower.

        Have a nice and resting holiday seasons and a happy new year 2013 Stephen.


      • Dear Stephen,

        I think you should write your own blog on MIA because you are blessed with a talent with words in conveying a unique experience and point of view, many interesting experiences on mental health to share and a gentle very humane modest and rich thinking about it all worth reading and rereading.

        Please accept my apologies for having ignored on 12 08 12 at 10:51 that you indeed wrote about unprofessional conduct of nurses:

        (…) when I would just get to sleep this one nurse would come in and shine the light in my face! With that kind of treatment you never get any sleep. One night I told her that if she shined her light in my face or the face of my roommate again I was going to get up and moon her. She ran down to the nurses’ station and wrote in my chart that I threatened to beat the s..t out of her. The charge nurse came to ask me why I was threatening her staff. When I asked what she was talking about she stated what the nurse had written in my chart. My roommate, who was awake at the time and heard exactly what I’d told the nurse originally about mooning her spoke up in my defense and quoted me exactly. The charge nurse told him to stay out of it because it was none of his affair. Of course, psych patients can’t be trusted because we always lie you know. I demanded for three days that her comment be removed because it was a blatant lie. They refused. I said that I wanted what I’d actually said entered into the file below her comment. They refused. So, in my record it stands that I threatened a staff person! You can’t win with these people.(…)///

        I am thankful for MIA to exists for many reasons, Stephen, but reading your comments and having a dialogue with you is not the least of it.

        All the best to you Stephen.


  7. I’m both amused and aghast at studies that use time to discontinuation as a primary (or the primary) outcome. I wonder if they have ever included placebos in discontinuation studies.

    (Or candy or ice cream, for that matter. A small dose, e.g. 1/2 cup, of Ben & Jerry’s every day — rotate the flavors, individualized to person’s preference — would score very well on time to discontinuation for most people, without too much metabolic impact. It might help improve a variety of other scored measurements too.)

    • Hi Phil,

      Actually, one of the oldest trick in spinning data in clinical trials has always been to just ignore the cases of discontinuation of treatment and the cases that didn’t came for follow up since discontinuation often means that the treatment didn’t delivered his promises to do more good than harm.