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1. Kane JM, Smith JM. Tardive Dyskinesia Prevalence and Risk Factors, 1959 to 1979. 

2. Carbon M, Hsieh CH, Kane JM, Correll CU. Tardive Dyskinesia Prevalence in the Period of Second-Generation Antipsychotic Use: A Meta-Analysis.

3 Solmi M, Pigato G, Kane JM, et al. Clinical risk factors for the development of tardive dyskinesia. 

4 Tenback DE, van Harten PN, van Os J. Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. 

5 Zai CC, Maes MS, Tiwari AK, et al. Genetics of tardive dyskinesia: Promising leads and ways forward.

6 Zai CC, Lee FH, Tiwari AK, et al. Investigation of the HSPG2 Gene in Tardive Dyskinesia – New Data and Meta-Analysis.

7. Bakker PR, van Harten PN, van Os J. Antipsychotic-induced tardive dyskinesia and polymorphic variations in COMT, DRD2, CYP1A2, and MnSOD genes: a meta-analysis of pharmacogenetic interactions. 

8. Patsopoulos NA, Ntzani EE, Zintzaras E, et al. CYP2D6 polymorphisms and the risk of tardive dyskinesia in schizophrenia: a meta-analysis. 

9. The American Psychiatric Association Practice Guideline for The Treatment of Patients With Schizophrenia, Third Edition. 2021. https://doi.org/10.1176/appi.books.9780890424841

10. Bergman H, Bhoopathi PS, Soares-Weiser K. Anticholinergic medication for antipsychotic-induced tardive dyskinesia. 

11. El-Sayeh HG, Rathbone J, Soares-Weiser K, Bergman H. 

Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia.

12. Soares-Weiser K, Maayan N, Bergman H. 

Vitamin E for antipsychotic-induced tardive dyskinesia.

13. Soares-Weiser K, Rathbone J, Ogawa Y, et al. Miscellaneous treatments for antipsychotic-induced tardive dyskinesia. 

14. Ad1elufosi AO, Abayomi O, Ojo TM. Pyridoxal 5 phosphate for neuroleptic-induced tardive dyskinesia. 

15. Kane JM, Smith JM. Tardive dyskinesia prevalence and risk factors, 1959 to 1979. 

16. Caroff SN, Leong SH, Roberts C, et al. Cumulative Burden of Illness in Veterans With Tardive Dyskinesia and Serious Mental Disorders. 

17. Carroll B, Irwin DE. Health Care Resource Utilization and Costs for Patients with Tardive Dyskinesia. 

18. Guy W. ECDEU assessment manual for psychopharmacology: revised. DHEW Publication No. ADM 76-338. Rockville, MD: US Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH Psychopharmacology Research Branch, Division of Extramural Research Programs; 1976: 534-537.

19. Chouinard G, Ross-Chouinard A, Annable L, Jones B. The extrapyramidal symptom rating scale. 

20. Kalachnik JE, Sprague RL. The dyskinesia Identification System Condensed User Scale (DISCUS): reliability, validity, and a total score cut-off for mentally ill and mentally retarded populations.

21. Casey DE. Tardive dyskinesia: pathophysiology and animal models. 

22. Margolese HC, Chouinard G, Kolivakis TT, et al. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction. 

23. Blanchet PJ, Parent M-T, Rompre PH, Levesque D. Relevance of animal models to human tardive dyskinesia. 

What do we know about TD? What is on the horizon? Take the quiz to learn more.

Tardive Dyskinesia: 8-Question Quiz on What We Know

Conversations in Critical Psychiatry is an interview series that explores critical and philosophical perspectives in psychiatry and engages with prominent commentators within and outside the profession who have made meaningful criticisms of the status quo.

 is the Dr Frances S. Arkin professor and chairman of the department of psychiatry, professor of psychiatry and medicine at Tufts University School of Medicine, and psychiatrist-in-chief at Tufts Medical Center. Dr Summergrad served as the 141st president of the American Psychiatric Association from 2014 to 2015. He is also a past president of the American Association of Chairs of Departments of Psychiatry and is Secretary for Finances of the World Psychiatric Association and a member of the WPA executive committee. Dr Summergrad’s research focuses on mood disorders, medical-psychiatric comorbidity, and health system design. He received the Distinguished Faculty Award from Tufts University School of Medicine in 2015 and the Leadership award of the American Association of Chairs of Departments of Psychiatry in 2018. He was elected to the Honorary Fellowship of the Royal College of Psychiatrists, their highest honor, in 2020. He is the lead editor of the 

 (2020, American Psychiatric Association Publishing).

In many ways, Dr Summergrad exemplifies the best of psychiatric leadership. He has a charismatic and warm persona, an in-depth knowledge of psychiatry’s history, an appreciation of its pluralistic roots in medicine as well as psychoanalysis, and a preference for taking the long view of psychiatry’s development as a field. I was pleased to be able to speak to Dr Summergrad about his intellectual development, his views on psychiatry’s identity, and the challenges facing the medical model and psychiatric classification.

 Perhaps we can begin with the trajectory of your intellectual and philosophical understanding of psychiatry, particularly how you have navigated the psychoanalytic as well as neuroscientific aspects of psychiatry over the course of your career?

 I have been thinking a lot about this, and I do not know that I can separate any of this from certain cardinal experiences of my life. So, I think we will have to take a little detour into my life story and how I entered medicine and psychiatry.

I am a child of the 60s in the sense that I was in college during the 60s. That was an extremely disruptive time in American history for a variety of reasons, and it became a disruptive time in my own life as well. I had been interested in psychiatry well before that, probably since I was 14 or 15 years old. For some reason, I was just pulled towards psychiatry. Maybe it was because I read 

in high school, or because I had also worked at a camp run by a Jewish social welfare organization. There was a cohort of kids at the camp who had emotional and social difficulties. As part of that experience, we learned a bit about how to work with kids who had emotional difficulties, and that also reinforced my interest in psychiatry.

I started college in 1967. Looking back on it, I doubt that I was clinically depressed, but it was definitely an emotionally turbulent period of my life. I was significantly thrown off both by where I was living as well as by my living circumstances. I hated Buffalo and its winters. Going outside in the winter there seemed like crossing Siberia to a New York City native. I was not really prepared for it. And I was a freshmen male living in gender segregated rental housing off campus. During that year, I took a course on the 

, which as you know is one of the foundational texts of Buddhism. I was very much drawn to that course, as well as to another course on Chinese history, but otherwise I felt very disconnected from school. Like probably a lot of other college students at that time, I started smoking cannabis. In the spring of that year, I took LSD—I am certainly not advocating for the casual use of psychedelics or cannabis here—and I had a profoundly religious experience. It was as if I had been dropped into Nirvana, perfection, holiness, oneness. It was a deeply mystical experience, and it also changed my thinking about the 

. It made me think a lot about neurobiology and consciousness, because if a tiny dose of a drug like this could change one’s perception so profoundly, what did that mean regarding how we understand the mind-brain relationship, and relevant to psychiatry, the etiology of mental illness?

Partly as a result of that, I then went on to study Zen Buddhism and considered training as a Buddhist monk. I ended up spending a couple of years doing very intensive Zen Buddhist meditation at a training center in Rochester, New York. There was no drug use of any kind and a fairly ascetic lifestyle. Towards the end of that period, I spent a year in a self-imposed isolation, in a liminal state, because I really felt that I needed to cut out the external messages of the dominant culture to discover what I really wanted to be and do. At the end of this period, I had a couple of important dreams and one of the dreams was extraordinarily powerful, a great dream in the Jungian sense, which basically resolved my dilemma. I woke up and my crisis was over. I knew exactly what I wanted to do and how to integrate the various strands of my life. I knew I wanted to go to medical school and to likely become a psychiatrist.

In medical school it turned out that I really liked medicine, and I ended up training in internal medicine for 3 years before I trained in psychiatry. The medical training left a deep influence. I was impacted by being in a medical setting where neuropsychiatric conditions were among the most common admitting diagnoses. When I was an intern, probably a third of the admissions to the medical service were due to altered mental status. I realized that in practically every rotation, the only thing I really cared about was the neuropsychiatric consequences of the medical conditions I was studying. So, I really could no longer resist the siren song of psychiatry, but I was impacted by my medical training, such that for me, the boundary between medicine and psychiatry has always been very porous.

 What sort of notion of psychiatry did you have at that time, and how was it influenced by your earlier mystical and meditative experiences?

: My sense of psychiatry was in part tied to depth psychology and psychoanalysis. Given my Jewish background, and given Freud’s own cultural Jewish identification, there was a pull towards psychoanalysis from a cultural standpoint, but there was also a pull towards it as being somehow central to psychiatry. 

 provided me with a way to merge my experiences with dreams, meditation, and psychedelics with my interests in medicine and science.

I went on to undertake psychoanalytic training at the Boston Psychoanalytic Society and Institute. Despite my psychoanalytic training, I thought psychiatry had to be profoundly anchored in medicine, and by medicine I am broadly including here internal medicine, neurology, as well as the neurosciences. For my residency I went to the most medically oriented psychiatric program in the United States, which was Massachusetts General Hospital. Tom Hackett, MD, was the chief there when I was a trainee. His view was that if psychiatry was not anchored in medicine, it was kind of homeless, from a clinical as well as operational standpoint, and I agree with that. I think it is unfortunate that a lot of the time as psychiatrists we end up giving away our connection to the rest of medicine and neurology. The other side of it is the risk that we may justify our existence as physicians by overvaluing what seemed to me to be a narrower 

. I think if we were more secure in our relationship with medicine, we might not see quite this tension within the profession.

 How did you reconcile psychoanalysis and neuroscience in your mind?

 Early in his career, prior to the development of psychoanalysis, Freud wrote a book called 

, which was officially published in 1950, well after his death. I felt that my interests in neurobiology and psychology came together in 

 which mirrors, especially in its critical seventh, metapsychological chapter, 

 Freud was really struggling with how to place his interest in depth psychology in the context of the burgeoning neurobiology of the late 19th century. The late 19th century was a fertile period: the neuron doctrine was being established. 

 produced his first drawings of neurons around that time. Freud attempts in 

 to use what he understood as the accepted neurobiological model and tried talk about how this whole apparatus works to generate mental states. I thought that he engaged with that issue in that book in a much more profound way than psychoanalysis has subsequently. Freud was severely limited by the neuroscience of his times, but he was convinced that a scientific explanation of psychological phenomena in terms of neurobiological phenomena was possible. He basically thought of psychologic states in parallel to the physiology of the brain that, while separate, they were “dependent concomitants,”

 and I think this central idea provides a potential means of reconciliation.

 In the mid-20th century, the psychiatrist 

 was commissioned by the World Health Organization to review existing psychiatric classifications. He noted in 

Recently, the attitude of many psychiatrists towards the conventional type of classification has become one of ambivalence, if not of cynicism… classifications based on the Kraepelinian system have continued to be used in some form or other all over the world. Many psychiatrists have done so under protest and expressing their disbelief in the working hypotheses underlying that system.

This description strikes me as quite applicable to our own times. The controversy surrounding the development of DSM-5 and the on-going search for alternative classification frameworks reveals just how deep the dissatisfaction is. What are your thoughts on why attitudes towards classification continue to be ambivalent in the psychiatric community, and what do you see as the path forward?

 The dynamic as described by Stengel does seem to exist. I think that we tend to get into a lot of unnecessary battles around classification, regarding how we classify and what we classify, as if these were not constructs imposed on real conditions. It is not that psychiatric disorders are not real. They are terribly real. All you need to do is take care of someone who is experiencing a severe episode of mania or catatonia, to know that they are profoundly and powerfully real. I tend to see psychiatric classification as more of a tentative and open-ended iterative process, subject to revision by evolving data and models of disorders. . This is a difficult task, as you know, we are dealing with things at multiple levels of observation. Take Research Domain Criteria (RDoC), for example. Even if you are going to use RDoC to do a research study, you still need to select and study a group of patients using some form of clinical categorization, whether it is something broad as mood disorders, or specific symptoms such as anhedonia, etc. There was recognition in the 1960s and 1970s, by the group of psychiatrists at Washington University in St. Louis as well as Robert Spitzer, MD, and colleagues that there needed to be some operational criteria to ensure reliability of observations. This recognition emerged in the context of many studies which had showed the poor reliability of various diagnoses at the time, such as the differences between the diagnoses of bipolar disorder vs schizophrenia in 

I think the development of our current nosologies in the 1970s was an understandable reaction against a lack of scientific rigor, at least around reliability. It starts becoming a problem when the operational constructs become reified as real, as valid. This will be relevant to our discussion regarding the medical model as well, because mental disorders are profoundly personal and intimate, and they affect one’s deepest sense of who one is. A psychiatric diagnosis can be heard as somebody saying that it is as if your intrinsic being is somehow medically defective or genetically defective; it is not just that your body is diseased, but that 

 are diseased, with the implication that you may be unchangeable.

Tensions emerge from well-reasoned and well-intentioned attempts to get closer to the truth about the causes, etiologies, and the treatments of disorders. I think that to a great extent, our diagnostic systems, whether it is DSM or ICD, have been helpful with regards to clinical practice and research, in allowing us to do systematized studies, because after all, we want to know whether the interventions are actually going to help somebody or not. We want to know with some degree of medical certainty whether we can recommend electroconvulsive therapy for the treatment of catatonia or for certain kinds of major depression, or whether we can or cannot recommend antidepressants for individuals who have bipolar depression. We cannot do that, we cannot really tell whether we are going to help patients or hurt them, unless we utilize reliable categories. These practical considerations are one of our primary obligations.

Again, I think that we struggle with this in part because the problem is so difficult, philosophically and intellectually, because it relates to the very things that we experience as the most intimate parts of ourselves, and also because we do not fully understand how the brain and the mind interrelate and interact. In fact, setting these difficulties aside, even if you look at general medicine, things are bit more clear-cut, but a large number of patients who present to general medical clinics have medically unexplained symptoms or they remain undiagnosed in terms of etiology. So, things are not always straightforward in rest of medicine either.

 The impression I get from your description of classification is that we need to take it a little less seriously. That we need enough that we can do our practical and scientific work with some structure and reliability, but it becomes problematic when we start to ascribe metaphysical importance to these operational constructs.

 Yes, that is right. When we reify these categories, we almost make them unchangeable objects. In order to begin to approximate validity, we need to be able to formulate hypotheses and then test them, and the only way we can do so is if we begin with some reliable way of describing the phenomena. Our diagnostic categories and our rating scales have a lot of limitations. We are relying on self-report, communications, physician observations. So, we always have to approach them with some degree of humility.

 Going back to your personal experience, when you were 18 years old and in that phase of emotional and existential turmoil, someone could very well have suggested that you were suffering from clinical depression and that you needed to see a psychiatrist. How do you think you would have reacted to that?

: In fact, I did get that message. That I was clinically depressed, and that I just needed to see a psychiatrist and be on the right antidepressant, and all of this would go away. I strongly rejected that message. The very last thing I was going to do at that time was to go see a psychiatrist. So, I understand where some of this resistance against the so-called medical model comes from.

If you had taken me at age 18 or 19, and had tried to look at my experiences at that time through the lens of a diagnostic or medical model, I would have agreed with the critics that the medical model was not the best frame for this. But if I had had to drop out of school because of intrusive obsessional thoughts or compulsions that may be quite different, and the medical model is in my view an appropriate frame of inquiry. Or perhaps I just do not have an accurate view of my 18-year-old self. I think that one critique of the medical model, as it is understood by many, is driven by a concern that we are judging individuals, pushing them away, not listening to their experience, and distancing ourselves from them by labeling them. We always have an obligation to listen and to be prepared to revise our thinking,

 The medical model in psychiatry is facing considerable opposition from many prominent critics. How to best understand the medical model is a complex issue, something we briefly touched on in your interview for 

 and in this series I have talked about the medical model in detail with 

 A question I would like to ask you is about the limits of the medical model. The concern around medicalization reflects a growing anxiety that more and more of our lives are being viewed through the medical gaze. It is perhaps to be expected that as medical practitioners we tend to focus on the ways in which the medical model can improve lives, but at what point does medicine say to itself, “Maybe we are not the best professionals to address this. Maybe this is a situation where we should let our colleagues in psychology and social work take the lead. Maybe this is a situation where the medical understanding of a condition should not dominate over or should not exclude a more psychological, social, or existential understanding of the phenomenon”? How can medicine be more reflective over its own limits and boundaries?

 Everything depends on what we mean by the medical model. To me, in its most basic form, the medical model is a hypothesis-generating method, the roots of which can be traced back to 

 among others. The basic idea is that there are signs and symptoms that assort together more likely than would be expected by chance, and we recognize them as syndromes. If we properly define what the syndrome is, we can begin to then investigate what causes it and how to treat it. This is an incredibly fertile thread that runs through all of medicine. This is the sort of thinking that serves as the foundation for 

’s pathological studies. It is a syndromic model, which leads to a hypothesis, which leads to investigation, and then the results of these investigations may force us to redefine our syndromes or redefine our hypothesis, so it is an iterative process as well. In this iterative process, diagnoses can be lumped together, or they may be split further, or rearranged in other unique ways. The syndromes are intended to have parsimonious explanations, to achieve

, “the supreme goal of all theory is to make the irreducible basic elements as simple and as few as possible.”

When individuals use the term medical model in psychiatry, I think what they mean is that psychiatrists are ascribing a medical cause to an individual’s experience or feelings. So when we, as psychiatrists, ascribe a medical cause to the feelings and experiences, we are referring to some ineluctable and unchangeable element about the individual, with the implication that their very essence is dysfunctional or pathological. That is, in my view, a mistaken understanding.

Do I believe that some of the experiences in the realm of psychic suffering are better understood as existential rather than medical? Absolutely, I do. I do not believe that every form of mental suffering or emotional suffering is a mental disorder, but do I believe that there are mental disorders which are best understood through the syndromic lens. DSM is a variant of this syndromic model, and it is a very useful tool to categorize mental disorders, a tool that also provides us with ways to validate our constructs, with validators such as course of illness, family history, genetics, biology, and a variety of other things that have been well-described by 

, among others. These validators help us put some guardrails around what we are postulating through the syndromic lens.

 I think the thing that concerns or worries many critics is that when something is viewed through that syndromic lens it tends to crowd out other ways of understanding it.

 It is an important worry, but it is not a necessary consequence of the syndromic view. Do all human experiences fall within the realm of medicine or psychiatry? I do not think they do, or that they should. I think that would be a mistake. In other words, there is definitely a risk that our diagnostic concepts can be over-extended and that everyday life can be medicalized. That is something we have to guard against.

I do think we have both an obligation to say, 

this is our best evidence of what is effective for this kind of entity

, and an obligation to recognize that not all emotional or mental states are best understood through this syndromic medical model. Neither the profession nor the general public is well-served by medicalizing ordinary human experience. It also does not mean that psychotherapy cannot be beneficial for developmental or existential concerns. It can be. Freud viewed the goal of psychoanalysis as converting neurotic “misery” into “common unhappiness.”

 The challenge we face is not to convert human unhappiness, what my Buddhist teachers would call, in the Pali Canon, 

 I really liked something you said in your presidential address to the APA

My bias is to look at the long, far view, if for no other reason than change is hard, complex, and always takes longer than we expect. We tend to look for instant transformation, analysis, and understanding, which is not always forthcoming, reliable, or desirable. This is especially true at times of great upheaval and uncertainty, which we are certainly experiencing in the sciences related to psychiatry, and more broadly in technology and culture.

It seems to me that the discourse in psychiatry has tended to fluctuate between extremes of enthusiasm and disillusionment, with this cycle repeating every 30 to 50 years. Do you think adopting the long view can help us avoid getting trapped in this cycle?

: Part of the reason why I think the long view is useful is that it allows you to see the changes that have actually happened. If we are too close to the events in question, it is hard to know whether meaningful or long-lasting change has taken place or not. I think if you take the long-view, the comfort that exists in contemporary culture with regards to talking about mental illness, the protections that exist within law, the reimbursement of care from insurance companies for psychiatric conditions (imperfect as it is), and the increased awareness regarding human rights in psychiatric care, all of those things to me represent advances in the course of history, but you cannot see them if you are too close to them. There is this story of Henry Kissinger, PhD, meeting with Zhou Enlai, the great Chinese prime minister, during the opening to China in the early 1970s. The story goes that they were making small talk before the visit and Kissinger asked Zhou, “What do you think of the impact of the French Revolution?” Zhou paused, and replied, “Too soon to tell.” I think that captures well my own sentiments.

 Speaking of the long view, in a 2013 editorial for 

, on the 100th anniversary of Karl Jaspers, MD’s 

; Mario Maj, MD, PhD, commented on the analogies between Jaspers’ historical context and our own. 

The most striking analogy is that nowadays, exactly like one century ago, the enthusiasm brought about by a period of exceptional progress of research in neurosciences is being followed by some disillusionment, due to the limited relevance of that progress to the elucidation of the pathophysiology of mental disorders.

 I do think that eventually we will learn a lot more about the organization and the functioning of the brain: how it works, not just at the genetic or the cellular level but also at the circuitry level, such that we would begin to link the activity of the brain circuits with certain states of mind. We can already do that to some degree already, but we will be able to do it better, with more precision and explanatory power.

That is not to say that everything can be or should be explained by neurobiology. You know, again, one of the implications of my psychedelic experience for me has been that it is hard to think about these issues with our current limited understanding of the mind-body problem.

A difference between where we are now and where we were a hundred years ago is that the late 19th century, early 20th century was kind of the end of that neuroscience period. 

, was born in 1856, the same year as Freud. The neuropathological work that the generation of Alzheimer and Kraepelin were doing peaked in the late 19th century and early 20th century in terms of its effects on psychiatry. The discovery of plaques and tangles in dementia, or the work arounds tertiary syphilis, for example. Neuroscience obviously continued on in the next decades, but its impact on psychiatry was very limited. In contrast, I think we are in a period now where the current wave of neuroscientific research is still offering more and more fertile hypotheses and lines of inquiry. For example, all the research going on around immunological and inflammatory processes in psychiatric disorders. It may turn out to be right or wrong, we do not know, but my timeframe to think about these things is more like 50 years, not 10 or 20 years.

 Any message for psychiatric trainees and early career psychiatrists?

 First of all, I think we are in a fabulous time for psychiatry. The number of US medical school graduates going into psychiatry has nearly doubled over the last 7 years. No other major specialty has seen such a large growth of new recruits. The field has enormous flexibility, richness, and breadth of interests. The stigma around mental disorders is going down and there is greater public discussion about mental health. One only has to look at the discussions related to mental health around the COVID-19 pandemic. This emphasis on mental health is really quite unprecedented.

We never know how our lives and careers are going to work out for us as individuals. If somebody had told me when I was a first-year resident in psychiatry at Harvard that I would become the president of the American Psychiatric Association, I would have laughed. I expect that our trainees will accomplish even greater things. Not only psychiatry trainees should have confidence in the field and in themselves, but their mentors should also have confidence in them. There is a great episode of 

 that I quoted in my presidential address.

President Bartlet is played by Martin Sheen and his communications aide, Sam Seaborn by Rob Lowe. They are playing chess while at the same time Bartlet is navigating a complex China-Taiwan diplomatic crisis. Sam is amazed and asks him how he does it. Bartlet answers, “You have a lot of help. You listen to everybody and then you call the play. [Rises to his feet] Sam, you’re gonna run for President one day. Don’t be scared. You can do it. I believe in you. [Looks at the board] That’s checkmate.”

So, that is kind of what I am saying to you, and to trainees who are younger than you: I believe in you, and I think that you can do amazing things. Not that I know about anybody’s individual future, but I can see that our trainees and younger psychiatrists such as yourself are going to have an impact on the field and the world around them. And that is a great thing, and you should feel confident that you have the ability to make a difference, and to do that in a way that is respectful of others, even those who are critical of the field.

The opinions expressed in the interviews are those of the participants and do not necessarily reflect the opinions of 

is a psychiatrist in Cleveland, Ohio, and clinical assistant professor of Psychiatry at Case Western Reserve University. He is a member of the executive council of Association for the Advancement of Philosophy and Psychiatry and has been actively involved in initiatives to educate psychiatrists and trainees on the intersection of philosophy and psychiatry. He is also a member of the

Dr Aftab and Dr Summergrad have no relevant financial disclosures or conflicts of interest.

The Standard Edition of the Complete Psychological Works of Sigmund Freud

. Hogarth Press; 1915. Volume 14:159-204.

2. Stengel E. Classification of mental disorders. 

3. Kendell RE, Cooper JE, Gourlay AJ, et al. Diagnostic criteria of American and British psychiatrists. 

4. Aftab A, Summergrad P. Paul Summergrad, MD, on the state of psychiatry. 

The Medical Model in Theory and Practice: Ahmed Samei Huda

September 4, 2020. Accessed May 18, 2021. 

On the Method of Theoretical Physics. The Herbert Spencer Lecture, delivered at Oxford, 10 June 1933

. Trans. Nicola Luckhurst. Penguin Classics, 2004.

9. Maj M. Mental disorders as "brain diseases" and Jaspers' legacy. 

In this conversation, a former APA president discusses mystical and meditative experiences, reconciling psychoanalysis and neuroscience, and tensions surrounding the medical model. 

Psychiatry and the Long View: Paul Summergrad, MD

 showed that treatment with a blended digital therapy targeting reasoning did not result in reduced self-reported paranoia at 24 weeks. However, it may improve paranoia in general.

SlowMo, a digitally supported reasoning intervention that consists of 8 face-to-face sessions lasting 60-90 minutes, takes an interventionist-causal approach to increasing cognitive behavioral therapy effectiveness by targeting casual reasoning processes in paranoia. The therapy was designed to build awareness of a tendency to jump to conclusions and develop increased belief flexibility.

“SlowMo also uses digital technology and inclusive, human-centered design to improve the user experience with the aim of enhancing engagement and adherence for the widest possible range of people,” wrote Philippa Garety, PhD, et al. “SlowMo builds on the encouraging findings for stand-alone and blended mobile phone apps for psychosis and, to our knowledge, is the first blended digital psychological intervention for paranoia (using digitally supported face-to-face therapy and a mobile app).”

A total of 361 participants with clinical paranoia from UK community health services were included in intention-to-treat analysis. Those with schizophrenia-spectrum psychosis and distressing paranoia lasting 3 months or longer were considered eligible. Of the 361, 332 participants provided primary outcome data, with 181 participants randomly assigned to the SlowMo group. Blind assessments were performed at clinics or in participant’s homes at 0 weeks for baseline, 12 weeks for postintervention, and 24 weeks for follow-up.

The primary outcome was paranoia, measured by the Green et al Paranoid Thoughts Scale (GPTS) total score at 24 weeks. While SlowMo therapy did not result in significant improvements in the primary outcome of total GPTS paranoia score at 24 weeks, secondary beneficial effects were found on this measure at 12 weeks.

“The results indicate that the treatment was effective, in part, through helping people to slow down their thinking and to worry less,” Garety et al concluded.

The study’s authors noted further work to optimize SlowMo’s effects is needed.

1. Garety P, Ward T, Emsley R, et al. Effects of SlowMo, a blended digital therapy targeting reasoning, on paranoia among people with psychosis: A randomized clinical trial. 

https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778159

While this digital therapy failed to meet its primary endpoint in a recent clinical trial, results suggest it may improve paranoia in general. 

Digital Therapeutics Improves Paranoia

A phase 2 trial of an adjunctive treatment for schizophrenia has stopped after failing to meet its primary and secondary endpoints. The treatment, CTP-692, developed by Concert Pharmaceuticals Inc, was a deuterated form of D-serine.

“The body of evidence in the field supporting D-serine as an adjunctive treatment for schizophrenia was compelling and led us to advance CTP-692 into a Phase 2 proof of concept study,” Roger Tung, PhD, president and chief executive officer of Concert Pharmaceuticals 

. “Unfortunately, we didn’t see the results we hoped for to support continuation of this program.”

CTP-692 was designed to improve on the efficacy and safety profile of existing schizophrenia treatments. Current research suggests that D-serine can improve outcomes for patients with schizophrenia, but it is accompanied by significant 

 Patients with schizophrenia also experience from cognitive impairments, and it was hoped that D-serine, which has shown positive effects on cognition in other contexts, would improve patient cognition without the renal risks.

The phase 2 trial was a double-blind, placebo-controlled study. It included 325 patients on antipsychotic medication. These participants were randomly selected to receive 1, 2, or 4-gram doses of CTP-692 once-daily, or a placebo. The trial took place over a 12-week period.

At the end of the 12-week period, the patients showed no improvement on the Positive and Negative Syndrome Scale (PANSS) compared to baseline scores, and the trial was discontinued. The company has also decided to discontinue study of this compound.

1. Concert Pharmaceuticals announces results from CTP-692 phase 2 trail in patients with schizophrenia. News release. Concert Pharmaceuticals Inc. February 1, 2021. Accessed February 17, 2021. 

https://ir.concertpharma.com/news-releases/news-release-details/concert-pharmaceuticals-announces-results-ctp-692-phase-2-trial

2. Concert Pharmaceuticals discontinues schizophrenia drug after trial failure. GlobalData Healthcare. February 3, 2021. February 17, 2021. 

https://www.clinicaltrialsarena.com/comment/concert-pharmaceuticals-schizophrenia-failure/

Is this phase 2 trial the end of the road for a potential new treatment?

A Potential Schizophrenia Treatment Trial Falls Short 

Elyn R. Saks is a lawyer and a professor at the University of Southern California Gould School of Law. In a book aptly titled 

 she tells how she managed to achieve this goal in spite of a chronic mental illness that was diagnosed, at different times, as paranoid schizophrenia and schizoaffective disorder, depressive type.

Elyn grew up in Miami, Florida, graduated from Vanderbilt, received a B Phil from Oxford, and a law degree from Yale-all with the highest distinction. This in spite of her struggle with a hydra-headed psychosis that came and went but never went away, and a “center” that disintegrated again and again, after being temporarily restored with the help of therapy, friendship, work, and psychotropic medication.

The first indications that Elyn might be heading for a difficult psychological life came while she was an undergraduate at Vanderbilt.

Her anxiety was constant, although less while doing academic work, from which she drew most of her identity.

Away from home, faced with new challenges and new expectations, Elyn began to “unravel.” She describes herself as “frantic during the day, sleepless during the night,”

 and she found it hard to concentrate and to think clearly. This daughter of fastidious professional parents let her hygiene slip, even as she realized that her body “stank.”

“My best guess,” she writes of that time, “is that my illness was beginning to poke through the shell (for lack of a better word) that helped me, indeed helps all of us, maintain a separation between what is real and what is not. For the next few years, that’s where things would precariously balance-me unwittingly trying to keep the shell strong, and my illness trying equally hard to break through.”

 In this psychic tug of war, substance abuse was not a contributing factor. Unlike many patients who begin to show signs of a major mental illness at her age, Elyn did not abuse drugs or alcohol.

In spite of a psyche that was increasingly blurring the boundaries between fantasy and reality, Elyn graduated from Vanderbilt with a perfect academic record, was named class valedictorian and won a Marshall scholarship to study ancient philosophy at Oxford-where her life really began to fall apart. There were trips to the emergency room, stays in psychiatric hospitals, psychiatrists and psychoanalysts, and psychotropic medications.

At Oxford, Elyn continued to excel academically even as reality became a tougher slog, and she retreated further into her fantasy world. She did not feel herself to be real, live, and continuous as R. D. Laing characterized the grounding of the ontologically secure person in 

 Nor did she experience others as real, live, and continuous. It was as if she lived behind a wall of glass-Silvia Plath’s bell jar comes to mind-cutting her off from what was going on around her. Elyn became frustrated and angry in her isolation and turned that anger against others, seeing ulterior motives where there were none. In fact, she had a coterie of loyal friends, teachers, and colleagues.

In her dreams, Elyn killed these friends, teachers, and colleagues because she was able to trick herself into believing that they wanted to kill her. This “killing” was how she feigned control when in fact she had ceded control to her illness, or her illness had taken it from her (most likely, it worked both ways). Elyn was self-deceived, depressed, paranoid, and psychotic much of the time:

Psychosis is like an insidious infection that nevertheless leaves some of your faculties intact; in a psychiatric hospital, for example, even the most debilitated schizophrenic patients show up on time for meals, and they evacuate the ward when the fire alarm goes off. So it was for me. Completely delusional, I still understood essential aspects of how the world worked. For example, I was getting my schoolwork done, and I vaguely understood the rule that in a social setting, even with the people I most trusted, I could not ramble on about my psychotic thoughts. To talk about killing children, burning whole worlds, or being able to destroy cities with my mind was not part of polite conversation. 

At times, though, I was so psychotic that I could barely contain myself. The delusions expanded into full-blown hallucinations, in which I could clearly hear people whispering. I could hear my name being called when no one was physically around-in a corner of the library, or late at night, in my bedroom where I slept alone.

While at Oxford, Elyn became the patient of a Kleinian psychoanalyst-Mrs Jones-with whom she formed a strong therapeutic alliance, and whom Elyn credits with being the “glue” that held her together, if precariously: “I was falling apart, flying apart, exploding-and she gathered my pieces and held them for me.”

 After 3 years of intense psychoanalytic work, and finishing her B Phil, again with high distinction, Elyn considered staying in England to continue therapy. But Mrs Jones encouraged her to return home. As expected with someone of Elyn’s psychic fragility, the prospect of losing this alliance induced great anxiety and led to a regression:

I go to my session. I threaten Mrs Jones with a knife. I am very psychotic and out of control. Mrs Jones is kind and gentle. She asks me for the knife and I give it to her. I start screaming. I throw myself against the wall. Mrs Jones and her husband restrain me. The ambulance arrives and takes me to the hospital. I become out of control again and am subdued. I am crying and sobbing that I will be leaving Mrs Jones . . . . Mrs. Jones had been the glue that held me together. With that glue soon to be gone, would I not shatter into a thousand pieces? The anxiety was overwhelming, and our sessions became more intense and hallucinatory.

You can’t leave. I won’t let you. Plupenitenary issues must be addressed. That’s a dress. Come home with me, please?

 I think, you see, that you make yourself confused because you want to avoid the pain of separation. It’s upsetting to think I have a life of my own, apart from you. You are trying to live inside me.

Elyn has fused with Mrs Jones by obliterating the person-to-person boundaries that nonpsychotic persons observe. She has crossed a line in her attempt to 

 the person who has provided the “glue” that allowed her to have a fledgling, brittle center of self. Note the neologism plupenitenary and the clang association addressed/dress, which are indications of formal thought disorder-an upshot of the psychotic mind’s need to create different words and different links between words.

While psychotic, Elyn was mostly lost to the world of reality, and had no insight. During a stable interval, she looked back on what that was like for her: “With psychosis, the wall that separates fantasy from reality dissolves; inside my head, the fantasies were real, and everything was actually happening. The images I saw, the actions I took, were all real, and it made me frantic.”

After graduation, Elyn left Oxford and Mrs Jones, returned to Miami and stayed with her parents until fall when she moved to New Haven to begin law school at Yale-where she continued her pattern of academic excellence and periodic ontic collapse. Her psychotic episodes became more severe and bizarre, requiring physical restraint and, eventually, her first antipsychotic medication, which she strenuously resisted verbally and physically. During the next few years, this drug (unnamed in the book), was replaced in turn by perphenazine, thiothixene, olanzapine, and clozapine, as eventual inefficacy and adverse effects demanded a change.

No drug completely erased Elyn’s psychotic symptoms, but each, for a time, lessened these symptoms and their impact, allowing her to finish law school, though not without taking a year off to deal with her illness. After Yale and several short-term jobs, Elyn was hired to teach at the University of Southern California Gould School of Law, where she was promoted to professor and given tenure. She married her longtime boyfriend, Will, who was as dedicated to serving her needs as any man possibly could be.

As Elyn lived with and against her illness, she became increasingly analytical and insightful as we can see in this cri de coeur: “I needed to understand what lay behind my terrible thoughts and feelings and how my psychosis served to protect me.”

 We might ask, How did she come to have these “terrible thoughts and feelings” in the first place? Whom or what did she need to be protected 

Elyn gives little space in her book to her parents, but what she does say about them seems probative. Both parents were emotionally distant from their daughter: “[T]here was a wall of appropriateness between us at all times; in fact, we’d spent years carefully constructing it, I on one side with my particular set of tools, they on theirs, with the tools they’d chosen.”

Had Elyn’s mother been “good enough,” in the Winnicott sense? And her father? At all stages of Elyn’s life, they seem to have been such vague presences, as if they were there, but not there for her. A family therapist noted that the parents had “made light of [her] illness and didn’t seem willing to accept its seriousness.”

 Elyn admits to being complicit in this cover-up: “I always did everything I could to 

 its seriousness: I cracked jokes, and laughed, and was gratified when they did the same. It was our way of handling it. It was our habit-and every family has its habits. The levity and irreverence made it possible for us to be together without everyone falling completely apart.”

 Laing might have said that Elyn and her parents had denied their being to save their being-

It eventually occurred to Elyn that a double trickery had ruled her life:

The illness-the entity-is always just off to the side, just barely out of my sight. But I know it’s there. And it tries to trick me into believing this isn’t the real Will, and this isn’t the real Steve [Elyn is describing Capgras syndrome, a delusion where she came to believe that her husband and closest friend were imposters], that reality isn’t reality, that I can kill thousands of people with my thoughts, or that I’m profoundly evil and unworthy. 

At the same time, I’m trying to trick the people around me. I’m OK. I’m functional, I’m fine. And maybe, sometimes, this determined effort to trick them tricks the illness itself. It’s like one big con. Steve says he’s never seen anyone who fights as I do. I don’t consider myself a fighter (and I certainly don’t come across as ferocious). But if he’s right, then perhaps in my childhood, and in this push-pull with my parents, one can see not only the beginnings of my illness, but the seeds of my health and strength as well. If I’m a fighter, perhaps it’s because that’s who they taught me to be

Without directly saying that her parents had a role in the development of her psychosis, Elyn, perhaps influenced by Laing and Bateson,

 considers that possibility. The “push-pull” with her parents sounds like the kind of mixed discourse, comprised of 2 incompatible and emotionally conflicting signals that Bateson characterized as a double bind. Bateson believed that such a conflict, 

, can, through a “twisting” of the psyche, lead the child to fragment reality and create the kind of psychotic thought, behavior, and discourse that Elyn lapsed into.

One can imagine Elyn as a child being in what Laing calls a state of ontological insecurity-profound anxiety about who she was and how she was to live-putting on a false self-“I’m fine, I’m strong; I don’t need you”-and the parents, caught up in their own self-absorption and blindness, wanting to believe her pose, responding with the same emotional coldness that they appear to have shown throughout Elyn’s life. This nonresponse to Elyn’s needs may have deprived her of the nurture necessary to trust the world sufficiently to take on the challenges of each new developmental milestone, leaving her mind and brain primed for developing a chronic mental illness.

Elyn knew that she would most likely never be entirely free of her illness. However, during a hospitalization at the Yale Psychiatric Institute, when she was initially floridly psychotic (“People are controlling me, putting thoughts into my head”

), and on a high dose of antipsychotic medication, she began to see that she could do something significant to help herself. After weeks of miserable and contentious confinement, her psychosis began to lift, and Elyn had an epiphany:

And then something threw a switch in my head, and I got it. I got it. The only barrier between me and the door out was me. I simply had to stop it. Stop voicing the hallucinations and delusions, even when they were there. Stop babbling incoherently, even if those were the only words that came to my lips; no, no, it was better to be quiet. Stop resisting; just behave. 

Being in a psychiatric hospital is nonsense, I thought. I am a law student, not a mental patient. I want my life back, damn it! And if I have to bite my tongue until it bleeds, I’m going to get it back.

By being “quiet” Elyn meant not just putting on an act but making an effort to at least mute her psychotic constructions, until she could face the world more realistically without them: “Maybe I couldn’t keep the thoughts from coming into my head, but I could organize them, and keep them from getting out. 

 For the first time, it seems, Elyn was asserting herself as an active agent against the illness itself, realizing that she had some complicity in the condition she found herself in, and some capacity to overcome that condition as well.

Near the end of the book, Elyn gives credit to Dr Freed, a psychoanalyst, who, she says, “helps me to understand how I sometimes use my psychotic thoughts to avoid the ordinary bad feelings that everyone experiences-sadness, rage, garden-variety disappointment . . . he tries to understand my psychotic thoughts as unconsciously motivated and meaningful (which of course they are).”

As she brings her story to an end, Elyn is still taking clozapine and is told by her psychopharmacologist that she will most likely have to take some antipsychotic medication for the rest of her life. She credits both psychoanalysis and psychopharmacology for the progress she has made. “While medication had kept me alive,” she acknowledges, “it had been psychoanalysis that had helped me find a life worth living.”

 For someone so long and so tightly in the grip of a psychotically transformed world as Elyn has been, the challenge of breaking that defensive structure is probably in some ways akin to breaking an addiction to a chemical substance.

Elyn’s descriptions of her psychotic (and normal) experiences are taken here to be primary data, in the way that numbers, and the statistical elaboration of these numbers, are considered data in the empirical approach to studying psychopathology. Hermeneutic analysis of what Elyn tells us about her fall into psychosis and her efforts to have a career and a life-her 

 of the phenotypes of the heterogeneous illness we call schizophrenia. Her narrative draws us into the interior world of the psychotic person, territory that few clinicians attempt to access or assess.

The Center Cannot Hold: My Journey Through Madness

. New York: Hyperion;  2007.
2. Laing RD. 

The Divided Self: An Existential Study in Sanity and Madness

. Baltimore: Penguin  Books; 1965.
3. Bateson G, Jackson DD, Haley J, Weakland J. Toward  a theory of schizophrenia. 

In spite of a chronic mental illness (schizophrenia)and a psyche that increasingly blurred the boundaries between fantasy and reality, this lawyer and professor graduated from Vanderbilt with a perfect academic record.

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