A Paradox Revealed – Again


Last week, an important study  (highlighted on MIA) was published in JAMA Psychiatry. Wunderink and colleagues published results of a follow-up study to one he had completed several years ago. In the initial study of  first episode psychosis, subjects were randomized to one of two treatment strategies: maintenance treatment (MT) in which they were maintained on drugs for the two year study or drug discontinuation (DR) in which the drugs were stopped and then restarted if symptoms recurred.

In their initial report, they found that the DR group had a higher rate of relapse.  They found no advantages to DR.  This study supported the standard practice of recommending that individuals remain on these drugs continuously for at least two years.

In this new study, they tracked these individuals 7 years after they had first entered the study. They defined three categories of recovery: symptomatic remission were those who had few or no psychotic symptoms, functional remission were those with good function (self-care, relationships, work), and full recovery were those who met criteria for both symptomatic remission and functional recovery.

At 7 years, there was a clear difference between the MT and DR groups: while both had similar rates of symptomatic remission (~67%), the DR group had a much higher rate of functional remission (46%) and full recovery (40%) than the MT group (19.6% and 17.6%, respectively).  Thirty-four (33%) subjects were on no or very low doses of drug.  Of those ~ 53% were in recovery.

Also of note, at seven years the MT group had the same number of relapses, they just occurred a bit later than in the DR group.

Martin Harrow’s study showed a correlation between neuroleptics and worse functional outcome but since this is a naturalistic study, one could not know if the drug dose caused the worse outcomes.  Wunderink and colleagues randomized their subjects to each treatment approach yet they also found that maintenance treatment was correlated with worse functional outcome.

Wunderink also found that total dose had an impact on outcome.  Lower average dose of neuroleptic – regardless of whether one was in the MT or DR group – was associated with better functional outcome without diminishing symptomatic improvement. 

Timothy Crow, a prominent British psychiatrist and researcher, conducted a somewhat similar study in the 1980’s.  In his study, he randomly assigned 120 subjects who had recovered from a first episode of psychosis with neuroleptics to maintenance treatment with drug or placebo.  In an initial paper published in 1986, his group reported a higher rate of relapse in the placebo group. However, in a later paper on 30 month outcomes, they reported a higher rate of employment in those randomized to placebo.  As they wrote in that paper, “It suggests the disquieting conclusion that the benefits of active neuroleptics in reducing relapse may exact a price in occupational terms.”

More recently, Gleeson and colleagues  reported on the effects of an intensive experimental intervention that was designed to improve adherence to neuroleptic treatment in a group of individuals with first episode psychosis. Their intervention was effective – more individuals remained on drug – and at 12 months the relapse rate in the experimental group was lower.  But similar to Wunderink, they report that at 30 months, there was no advantage with regard to relapse rate for the experimental group and their vocational outcomes were worse.

I do not know who reads my blogs. I know that some of you do not need me to convince you that these drugs have serious problems.  I want to, for a moment, intentionally address those of you who do not know what to make of the disparate messages you may read or hear, those who think that Whitaker and others make some compelling points but have not been able to walk away from the prevailing clinical narrative, and those who are wondering how to translate these studies into practice.  I am still a practicing psychiatrist. I will go to work tomorrow and have these difficult conversations with the people who come to see me.  This is how I am currently making sense of this.

First of all, there is a wide variability in outcome and response.  I continue to believe that there are those who benefit from these drugs in both the short and long term.  I am not able to accept the notion that neuroleptics are no different from other tranquilizers since they seem to yield a specificity of response – a decrease in voices, an increase in coherence – in someone who is appearing fully alert. But this is only for some and there are others for whom the response is not so great and there are those who recover without taking them.  Unfortunately, we have no way of knowing who these people are.  

In a situation where outcome is so variable and hard to predict, it seems imperative to avoid algorithms and directives and maintain an attitude of active shared decision making with the individual and her support system.  “Relapse” is a construct that varies from individual to individual. The risk, therefore, needs to be considered on an individual basis.

Secondly, dose matters.  We have known for at least twenty years, that low doses are as effective as higher ones.  Many of the most troubling side effects are dose related.   Wunderink found that those in the discontinuation group had overall less exposure to these drugs. It may have been this lower exposure, rather than the targeted dosing strategy, that had the greatest impact.  If someone chooses to take one of these drugs, start low and go slow.  Consider dose reductions.

This is important. Right now, there are an increasing number of articles in the professional literature focusing on the use of long acting injectable (LAI) drugs.  This is in no doubt related to the fact that (in the US) with one exception, the current neuroleptics still on patent are LAIs.  This will be the next big push –  to prescribe LAI’s since they reduce relapse. 

This does not need to be a polarized discussion for or against the use of these drugs.  I doubt there is one correct answer.  However, it is important that everyone involved remain knowledgeable about the available evidence.


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. Thanks for your article. Just one thing — how long are the LAIs designed to last? I am fearful of what the consequences might be if this becomes standard treatment for the non-compliant (aka misbehaving upstarts who have the radical philosophy of “my body, my choice”).

  2. Thank you for writing this article. It strikes me a good place to start, regarding who should be weaned off these drugs, is to look at whether the use of antipsychotics was started because of antidepressant or ADHD drug use or withdrawal since technically, according to the DSM, that should have precluded a bipolar diagnosis and use of antipsychotics in the first place. But I’ve noticed the main stream US medical industry is still claiming antidepressants “unmask” bipolar. The truth is they can cause mania or hypomania in anyone, including someone on an antidepressant for smoking cessation only.

    And I know in my case, and it seems the studies are coming in showing mine is typical, the withdrawal symptoms can show up much later than the DSM states. And that goes for antidepressant, lithium, and antipsychotic withdrawal.

  3. These studies raise so many questions. Left unmedicated, how long do extreme symptoms persist? Does anyone know how long it takes for receptor sensitivity to develop? When people are discontinued from anti-dopaminergic agents, what percentage relapse and in what time frame. How long do relapses post discontinuation (which I’m assuming reflect drug withdrawal) last? Has anyone tried omega-3s and/or N-acetylcysteine? Evidence-based medicine is suppose to be interventions based on information. One would hope that these studies would prompt the NIH to fund research. When professionals don’t have answers is the ethical thing to do to inform patients and have them make decisions? (Of course, this will undermine the placebo effect.) I don’t remember ever discussing this issue in graduate school.

    With regard to anti-dopaminergic drugs being tranquilizers, clearly they are not. They work to turn off the delusions and hallucinations when people overdo it with cocaine as well. (The mechanisms for the cocaine hallucinations are pretty well worked out.) I also don’t think we know for sure why they shrink brain. My money is on the idea that dopamine is the trigger for astrocytes to release growth factors, but who knows. Does one tell patients about the Ho et al. study? Is this part of informed consent? I think psychiatrists are in a very hard position. Thanks for the post.

    • I don’t know that their position is all that hard. I think they put themselves in a hard position as a profession by asserting things that aren’t true. It seems to me the research is pretty clear about what it suggests, even if the reasons are unclear: the less medication is prescribed (on the average), the more likely it is that the client will be able to maintain a functional social life, and the level of “symptoms” will be relatively unaffected. This is what the Soteria House experiment demonstrated rather conclusively back in the early 1970s. The results haven’t changed since then. If you care about the client’s ability to function in society, the results are fairly clear.

      If psychiatrists are honest about what the research says, it seems clear that they will need to be much more conservative about prescribing antipsychotics, even if they believe 100% in the “chemical imbalance” theory. It appears that “antipsychotics” don’t rebalance dopamine, they appear to throw the balance off. So if antipsychotics are used, they should not be first line interventions, they should be used at as low a dose as possible, and clients should be weaned off as soon as is practical to do so. Much as they do in the Open Dialog program, which has the world’s best success rate with “psychotic” clients.

      Sounds fairly simple to me.

      —- Steve

    • Well, it’s not like psychiatry didn’t put itself there in the hard spot. Now it has to deal with what it helped create. Unfortunatley, now millions of other people also have to deal with the problems, through no fault of their ownn. People on the receiving end of the so-called “treatment” didn’t put psychiatrists there. Psychiatrist put themselves there by their own choice.

      Fortunately, there are some, like Dr. Steingard, who are willing to struggle to try to make some heads and tails out of the overwhelming problems we are experiencing because of the poor choices and decisions made.

  4. Sandra,

    Assuming the following (your) hypothetical:

    “First of all, there is a wide variability in outcome and response. I continue to believe that there are those who benefit from these drugs in both the short and long term. I am not able to accept the notion that neuroleptics are no different from other tranquilizers since they seem to yield a specificity of response – a decrease in voices, an increase in coherence – in someone who is appearing fully alert. But this is only for some and there are others for whom the response is not so great and there are those who recover without taking them. Unfortunately, we have no way of knowing who these people are.”

    Question: How does any psychiatrist justify the use of force, if there is no way to determine who might “benefit?”

    And much more importantly, who might be gravely injured?


  5. Hi Sandy,

    I’ve been also reading your comments at 1boringoldman and I appreciated your pointing out the lack of evidence for certain claims being made there that I have found quite upsetting given Dr. Insel’s recent announcement admitting DSM INVALIDITY and having read Gary Greenburg’s very enlightening book, THE BOOK OF WOE, about the lies and junk science behind the DSM and DSM 5 in particular in which he interviews and quotes Dr. Allen Francis quite a bit. Similarly, I have ordered a new book by very prominent experts like Stuart Kirk and David Cohen called MAD SCIENCE:PSYCHIATRIC COERCION, DIAGNOSIS AND DRUGS, which covers similar information, which I highly recommend (On Amazon and discussed on the web). There are many others out including one called CRACKED by Dr. James Davies also exposing the fraud of the DSM and how BIG PHARMA bought out psychiatry, causing huge harm to so called patients/victims. I realize this was done by those in power like Robert Spitzer, Allen Francis, government officials and others, so this is not meant to attack you. I am just very glad that this predatory medical/industrial cartel with its dangerous junk science is coming to light since so many have been harmed, especially children in the guise of mental health and medicine like Joseph Beiderman’s child bipolar fad fraud that resulted in the infamous death of Rebecca Riley and many other children and toddlers no less on neuroleptic cocktails.

    I would like to ask your opinion of ECT since it seems to come up quite a bit at Dr. Nardo’s web site. Given the fact that Dr. Nardo seemed to applaud Dr. Bracken’s article on the need for a new paradigm in psychiatry and the fact that this article showed that real ECT was no better than sham ECT in terms of benefit, I question why there are so many cheerleaders for ECT on Dr. Nardo’s web site. Well, the answer was quite clear to me once I checked out the web site a bit more, but I will hold off saying much more until you can hopefully give your views about ECT if you would be so kind. Your high opinion of Dr. Nardo and others’ led me to start reading his web site. I was very impressed with his work exposing the fraud with many psych drugs, but red flags started going off as discussions of ECT became more prevalent and eerily familiar.

    Also, I saw that you were involved in writing a book covering neuroleptics and their side effects quite some time ago listed at Amazon. I would like to know please how you would compare neuroleptics and ECT in terms of the brain damage and other harmful effects that both of these brain disabling treatments cause per my hero, Dr. Peter Breggin and many others.

    I appreciate the fact that you continue to struggle with these issues, but I must say I continue to be against bogus, life destroying DSM stigmas and the current lethal, coercive brain damaging treatments of biopsychiatry.

    Are you making much progress with Open Dialog these days? If I recall either R.D. Laing and/or Loren Mosher used regular, non-expert people to provide much of the contact among the “patients” of both these famous doctors. The reason I mention this is because I realize it must be hard for you and other limited number of experts where you work to find the time to do such a seemingly labor intensive approach to psychosis. I’m wondering if a peer/trained volunteer approach might help including various family members taking certain shifts.

    I’m just making suggestions because I hate to see biopsychiatry go on with business as usual and I must say I am very disappointed when reading Dr. Nardo’s claims.

    I would appreciate hearing your thoughts on the above. It was very brave of you to come back after the reaction to your last post and that’s why you are admired and respected by most if not all of us for hanging in there when people who have been gravely harmed by psychiatry get traumatic triggers from some of the topics discussed. I imagine you are used to that in your work though I’m sure it doesn’t make it any easier to take. So, I want you to know that I truly admire and appreciate your hard efforts to learn and do the right thing. As Matthew Cohen said recently in a heated debate, I would rather have you where you work any day than the typical BIG PHARMA rep doctors pushing the latest lethal drugs on patent in toxic cocktails and highest doses. But, I also hope that this horrible paradigm will change some day because I don’t believe medicalizing human life, problems, crises, sorrows and other challenges is any solution whatever. Dr. Joanna Montcrieff and others address this issue in DE-MEDICALIZING MISERY and MADNESS CONTESTED among others.

    Finally, I find it ironic that you said you dropped psychoanalysis long ago due to its lack of science while pursuing biopsychiatry for its perceived science. Do you find that ironic now? I sure do! I still think there is plenty of room for a kind, compassionate, empathic person talking to people to help them with common sense problems/solutions that is not so common in our alienated, capitalist, materialistic society; validating abused/traumatized women and children or even work and school victims of bullies while providing practical advice, referrals, etc. though that probably wouldn’t fit your definition of science? Or have you reconsidered what might be scientific when it comes to messy humanity with all of its complex emotions, sorrows, joys and challenges?

    Again, thanks for being here and there is no rush if you are kind enough to respond.

  6. Sometimes I wonder if we shouldn’t just rip up all we know about ‘schizophrenia’ and start again; from the person, from the symptoms, from the beginning, perhaps taking, what Jo Moncrieff calls, a drug centered approach to these medicines, as opposed to a disease centered approach. These are not diseases we are dealing with, the drugs are not antipsychotic but rather drugs with effects on dopamine systems, a by-product of which might be symptom control. And if there is no disease there is no need for life long adherence, but a real need to develop services that get people understanding their symptoms in the context of their experience, providing problem solving, functional rehabilitation, family interventions, mindfulness based treatments, spiritual care… basically anything which prevents this chronicity. The current system seems to promote chronicity through the promotion of a disease model. The drugs may play a role but only as tools to manage symptoms and therefore built into careplans from the beginning should be an exit stratergy for helping people get off the drugs without provoking another relapse. The science as you suggest seems to support this view. Very little science really supports the traditional disease based model of psychosis care.

  7. Okay, the question that keeps bothering me about all of this is: If we know that people do better on lower doses, and their overall, longterm outcomes are better on lower doses, why do so many psychiatrists drug people with high doses, sometimes using more than one drug?

  8. I presume we are talking about “The Myth of the Chemical Cure.” And as someone who is not trained in psychiatry, other than two psych classes in college, and the last eight years researching the psycho / pharmaceutical industries so I could medically explain how doctors made me sick to cover up an easily recognized iatrogenic artifact. But who had two children win golds at regional and state science fairs (where the scientific method is stressed as invaluable). My heart went out to Dr. Moncrieff when reading her book.

    I understood from reading it, and from the lived experience of having been made ungodly sick by neuroleptics, that all the research she was searching through was work NOT based on the scientific method. And I felt her angst, in what seemed to me at least, to be her attempt to mentally come to grips with the fact that her industry was wrong about the effectiveness and safety of the antipsychotics. And I realize it must be very difficult for the ethical, but apparently big Pharma misled, psychiatric professionals to come to grips with the reality that in fact they were causing their patients’ illnesses, rather than curing them.

    But as a mom who understands the scientific method, and knew exactly how and when the neuroleptics made me sick, I noticed that almost none of the psychiatric research in the book addresses the reality of withdrawal symptoms or withdrawal induced psychosis, thus almost none of it is of any true scientific value. And I wasn’t certain Dr. Moncrieff realized this, although she may have.

    It’s been over a year since I read her book, so I may be remembering it incorrectly, but what I garnered from the book was, point blank, the total lack of scientific validity of all the psychiatric research. You have to have a control group, otherwise you have nothing with which to meaningfully judge the effects of the drugs.

  9. There seems to be very little acknowledgement of the link between electroshock and epilepsy (which has been my own experience, sadly). There are available studies suggesting this link, including one that asserts that post-ECT epilepsy is way under-reported. From a common sense point of view, it certainly seems possible that inducing seizures would cause seizures. My psychiatrist denies this (big surprise!) but my neurologist confirms he sees lots of strange neurological symptoms after ECT. I’m much more inclined to listen to a neurologist.

      • “It’s like the difference between astronomy and astrology.”


        Duane, that’s so very true…

        And, now, to illustrate that point for oneself, one can just watch the head of the NIMH, presenting his TEDx Talk, at Caltech:


        In barely over ten minutes’ time, he does a most fascinating job of promoting his field’s new spin on its old claim of addressing “brain disorders” (their “chemical-imbalance-in-the-brain” theory was so weak, at last, it threatened to stall psychiatry’s eternal hope for legitimacy).

        Insel now leads his field of U.S. government researchers, by referring captive audiences to a *supposed* coming technology, that shall (theoretically) offer early childhood “prediction” and “prevention” of would be adolescent “Neuropsychiatric Disorders”; yet, he *never* offers even one single hint as to how such “predictions” can ever be made.

        Only, he insists that his brethren are making progress.

        His Powerpoint demonstration briefly introduces the concept of, “DISORDERS OF THE HUMAN CONNECTOME.”

        So, I’ve been doing a bit of research, beginning with Wikipedia (via their page on ‘connectomes’: …en.wikipedia.org/wiki/Connectome).

        There, we can read,

        A connectome is a comprehensive map of neural connections in the brain.

        The production and study of connectomes, known as connectomics, may range in scale from a detailed map of the full set of neurons and synapses within part or all of the nervous system of an organism to a macro scale description of the functional and structural connectivity between all cortical areas and subcortical structures. The term “connectome” is used primarily in scientific efforts to capture, map, and understand the organization of neural interactions within the brain.

        Ultimately, Insel crosses out these two terms, “Mental Disorders” and “Behavioral Disorders” with a red line — and offers “brain circuit disorders” instead.

        In the end, he quotes Bill Gates on the rise of new technologies and the tendency of such, to come within a decade’s time.

        This is the new “Decade of the Brain” after all.

        Not once does he mention possible environmental factors affecting human brains.

        Oddly, he does not do so even when mentioning “PTSD”.

        (IMO reasonable people who are studying kids and aiming to prevent their would be eventual development of “PTSD” will seek to eliminate likely sources of traumatic events, in their environment — e.g., child abuse within the family, bullying at school, gang violence within the community, etc..)

        To realize he’s speaking to an audience at Caltech (which should, of course, be quite interested in whatever new technology he supposedly has up his sleeve), and that, apparently, no one questions him nor voices any objection to what he’s saying, is to wonder: Is he not, in fact, the U.S. government issued version of the Emperor Who Has No Clothes?

        Here I leave you with just a bit more from Wikipedia:

        The phrase “emperor’s new clothes” has become an idiom about logical fallacies.[28] The story is an example of what happens because of pluralistic ignorance.[29] The story is about a situation where “no one believes, but everyone believes that everyone else believes.”[30]


        Reading your comment, I couldn’t help but recall Nancy Reagan’s highly publicized consultations with astrologer, Joan Quigley, after President Reagan was shot.

        According to the Wikipedia page, on Quigley, she “stayed on as the White House astrologer in secret until being outed in 1988 by ousted former chief of staff Donald Regan.”

        Fortunately, she (Quigley) wasn’t applying for U.S. government research grants.



    • Francesca,

      You are absolutely right. I just found post-ECT epilepsy to be one of the major consequences of ECT along with the tons of other brain damaging effects that are ALL under-reported as in not admitted at all by the great shock doctor promoters. It certainly makes sense that this would occur after such seizures are deliberately induced. See the articles on ECT I posted above.

      I read elsewhere that doctors do all in their power to help epileptic people avoid seizures with medications, etc. because they are known to be very harmful to the brain. So, to deliberately induce them as a supposed treatment is barbaric, horrific and brain damaging as is typical of biopsychiatry’s fascist treatments for the purpose of social control and not medicine in any way, shape or form when such oppressive toture treatments are forced on unsuspecting people via without consent or without INFORMED consent.

  10. Thanks for sharing your reflections, Sandy 🙂
    Thank you, Donna and Jonah for all that information and links regarding ECT! I have just this second downloaded 2 books regarding the DSM and ECT. I have been so occupied with drugs their dangers, deaths etc that I have kind of left ECT on the sidelines because it is another huge area of human rights abuse and I due to lack of hours in the day thought I will leave that to other super competent activists, but you have gotten me going 😉

    • Olga,

      Thanks for your kind and encouraging post. I am honored that someone of your stature and repute would be influenced by my input and I am also very encouraged that someone like you would see the huge threat of the growing horrific comeback of deadly, barbaric ECT presents as the lethal psych drugs are more exposed. I’ve also read about the equally horrific comeback of lobotomies and so called brain operations with life destroying results per usual.

      These atrocities have been mainly perpetrated against women and the elderly, but the shock doctors are now trying to prey on children just like those poisoning those they fraudulently stigmatized with drugs and other tortures/human rights violations in the guise of medicine for bogus “INVALID” stigmas.

      Thus, I believe that any and ALL of psychiatry’s barbaric, brain damaging, disabling treatments must be included in any discussions of human rights, outlawing torture, etc.

      As you can see from above, I, too, only became aware of the CURRENT huge threat of ECT thanks to Dr. Peter Breggin, who remains my hero as I’ve said many times for this and other reasons!!

      I would appreciate it if you would share which books you downloaded on the DSM and ECT in case I have missed them.

  11. Dr. Steingard, ECT is what it appears to be at first blush: in case this feeling has disappeared for you…inherently dangerous and a very far out idea, almost otherworldly.

    By the same token, the analogy with persons wishing to have their healthy limbs amputated seem not to break down. And wouldn’t it be the scientific thing to do with all supposedly good things to create parallel test groups with patients in no way in need of the additive, whether med or voltage, and compare outcomes with those speculated about–perhaps,to sustain careers?

    I feel the community offered you a great shortcut to narrowing down your reading.

  12. Hi Sandra,

    Thanks again for a balanced and interesting approach on this blog from an actual clinician. I particularly agree with your point about treating each person individually. Serious short term risk often has to be balanced against the potential for negative long term consequences. There isn’t an algorithm and like you, I still believe that neuroleptics are helpful for some people and should be used in some situations.

    I wanted to point out something about the Wunderink study which I don’t think was apparent from your post. It is my understanding that the trial participants were treated with a neuroleptic for the first 6 months and once stable were then randomized to either drug reduction or maintenance arms. It is an important point because it means that the data only directly comment on this specific group. That is those with first episode psychosis who become stable for 6 months with neuroleptic treatment.

    I think the study is very interesting and valuable, but accurate understanding of the context in which the data directly apply is critical. It is certainly not by itself evidence that supports not using neuroleptics at all. In fact, one could argue it supports rapid stabilization on neurleptics followed by judicious attempts to reduce dosage or wean off completely. For a balanced editorial on the article see, http://archpsyc.jamanetwork.com/article.aspx?articleid=1707649. Unfortunately many will not be able to access it due to journal paywalls, but some may be able to read it.

    I understand that there are many types of data that people cite in regards to the negative consequences of neuroleptics. It isn’t my intention to get into that, just to point out that this article applies to a narrow spectrum of patients with first episode psychosis who were successfully treated with neuroleptics prior to being weaned off.