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Nev Jones, PhD, is an assistant professor in the Department of Psychiatry at the 

, University of South Florida, and a faculty affiliate of the 

Louis de la Parte Florida Mental Health Institute

. An applied mental health services researcher, her expertise includes the social and cultural determinants of pathways to and through care, early intervention in psychosis, multi-stakeholder perspectives on mental health services, and the relationship between poverty, education/employment and longer-term outcomes. She is currently a primary investigator (site PI) on grants funded by the 

Patient Centered Outcomes Research Institute

National Institute of Disability, Independent Living and Rehabilitation Research

Although I had known about Jones for some time and had interacted with her on social media, I remember the exact moment when I found myself in complete awe of her. It was when I read David Dobb’s 

 “The Touch of Madness,” a profile on her life and career.

 It remains one of the most remarkable and thought-provoking profiles I have read as a psychiatrist. The article describes her experiences of psychosis as a doctoral student in philosophy, the ways in which her social circle reacted, her encounters with the mental health system, the derailment of her career as an aspiring philosopher, and the beginning of her career as a brilliant psychologist, who has used insights from her own lived experience to shed light on the ways in which our current practices are failing those who need our help the most.

Without repeating your life story, which can be gleaned in the 

, how has your own experience with schizophrenia spectrum psychosis shaped your understanding of what psychosis is and of the role played by culture and stigma in shaping this experience and the outcomes?

 I tend to situate my views on experience within the standpoint theory literature, ie, that knowledge, in general, is socially situated, and that individual and collective identities and experiences shape (but, of course, do not simplistically determine) one’s understanding of the world, self, and others, and one’s particular attunement to relations of power (what speakers and what conclusions one finds to be credible). All of us, of course, have our own sets of experiences and identities—some socially or structurally imposed and others that we explicitly take on.

When it comes to psychosis specifically—both the experience itself and the clinical relationships in which one then finds oneself—a few things really stand out for me. One is a deep realization of (and then attunement to) the complexities of the experiences that fall under the 

 umbrella—the many and variable forms they take, certainly, but above all, their liminality. By liminality I mean that, for many of us, language quickly breaks down, as dothe psychological constructs and categories on which we tend to rely. Although it could also be the case that the experience of psychosis really only exposes limits and fissures that are already there, but masked.

I feel like there was an enormous disconnect between my experiences and the more mainstream conceptualization of psychosis, as well as key symptom categories of 

. Not just because the assumed distinctions between delusion/belief and hallucination/sensation, or between thought and the spoken word easily dissolve in actual experience. But also because of the ambiguous, indeterminate role of agency, our own agency, as we struggle to apprehend these limits. More on that later.

The second key issue for me is power. Power both in the sense of force (physical and legal) as well as relational power as it circulates between individuals. We all deal with, and are constantly immersed in, relations of power, but as a patient navigating psychosis, we tend to experience this in particularly deep, generally subjugating, ways, eg, through very strong forms of social rejection and exclusion, fear, misrecognition, assumed impairment, and disability. Then, at a more macro level, invisibility and devaluation when it comes to thinking about social justice, socioeconomic reform, and so on. If anything, I have experienced this in a much more attenuated way than so many other individuals I know, or with whom I have subsequently met or worked. As an interviewee in a study put it, we’re “throw-away people.”

So that is at least a start. Both these areas—phenomenology and then power—are pretty clearly at the heart of my research.

 Starting with psychopathology, can you say more about your 

 on the unacknowledged complexities of psychosis and schizophrenia?

 I should start by emphasizing that psychosis is, of course, an umbrella term that includes an absolutely huge array of different alterations of experience, or alterations of patterns of experience. Yet we, and psychiatry and the allied psy-sciences, by and large do not engage with this breadth, depth, and variety at all. Philosophers of psychiatry love to refer to a 2006 article by Nancy Andreasen, MD, PhD, juicily titled “

DSM and the Death of Phenomenology in America

.” I think it is actually worth quoting her analysis directly. One of the major problems she identifies is a very fundamental misunderstanding of what the DSM does, namely that3:

The criteria include only some characteristic symptoms of a given disorder. They were never intended to provide a comprehensive description. Rather, they were conceived of as “gatekeepers”—the minimum symptoms needed to make a diagnosis. Because DSM is often used as a primary textbook or the major diagnostic resource in many clinical and research settings, students typically do not know about other potentially important or interesting signs and symptoms that are not included in DSM.

I would word this more strongly. Most clinicians with whom I have trained, interviewed, or otherwise interacted have very explicitly been trained to view DSM symptom lists as comprehensive. A few indicators have, in essence, become the thing itself in working clinicians’ minds. The consequences of this, only some of which Andreasen herself 

, cannot be overstated. Misunderstanding, misrecognizing, reducing, and over-simplifying psychosis can and does impact everything from translational neuroimaging (dependent on the use of standardized measures) and new drug development, to clinical conceptualization and the capacity of clinicians to engage more deeply with clients. Clients who feel profoundly misunderstood may never open up in therapy or consultations.

You have done some fascinating work on the phenomenology of psychosis. For instance, on the nature of 

 in the phenomenology of psychosis. What are some of main findings and conclusions of this body of research?

 After a very difficult period, I got into grad school (in psychology), started doing research, and also facilitated Hearing Voices Groups. (I suppose I should really stress that had you told the Nev of, say 2007, that she would be become a professor of psychiatry, she would have told you that you were completely out of your mind). As a patient earlier on, I think it is fair to say that I honestly was never very sure that I was experiencing psychosis/schizophrenia, precisely because it seemed to diverge so profoundly from the standard SCID questions, for example. At least as I heard and understood them. But then, once I started to interact with other people, and not just a random few, but a lot of individuals, through research, peer support and facilitation, and eventually training and outreach, I began to realize “this is not just me at all.”

In fact, at multiple points, I felt heartbroken hearing other individuals’ stories and the extent to which they felt they could not open up, how they never even tried to describe so much of their experience to clinicians, or how they had long ago given up trying. Many were folks who had been in the public mental health system for decades. They had worked with dozens and dozens of different clinicians and social workers. The areas of misunderstanding or silencing or invisibilization took different forms. I listened to this, which really is what informed my initial research.

Just as one example, I briefly mentioned the Hearing Voices Groups at a large service user gathering. An older woman raised her hand and asked if I could talk to her after the meeting.

“You said voices group,” she said, “can you say what you mean by that?”

“Well,” I responded, “they take a huge variety of forms and voices is itself maybe not the greatest term. Some individuals literally hear a voice; for others it is more quasi-auditory; for others it may even be a color with words jumbled in it. For instance, one of the members of my group refers to a group of her voices as a ‘wall of color’ that comes at her. Does this help?” I asked.

At that point, she literally broke down crying and then proceeded to talk about the decades she spent thinking that, in spite of a diagnosis of schizophrenia, she did not really hear voices, she did not know what to call them, and that something was wrong with her because even her schizophrenia was not real.

These experiences, as well as my own, inspired me and galvanized meto try to elevate these experiences and their complexities. So that is what I did—a series of qualitative publications on the aspects of psychosis and schizophrenia that I felt had been extremely neglected, dismissed, and devalued.

Looking at your publication history, it seems like you then moved away from phenomenology and, for the past 5 or 6 years, have mostly published research on mental health services. Would you say that these more recent studies and publications have more to do with what you referred to as relations of power?

 Yes, precisely. I think I felt very strongly that I needed to do what I could to, as I say, complicate extant understandings of psychosis. Having tried my best to do that, I wanted to tackle the more macro issues of power, engagement, and outcomes in services. And, beyond that work designed to deepen our understanding of ways in which structures and institutions (eg, welfare policy, income inequality, structural racism, and xenophobia), shape psychiatric discourse and the trajectories of those who end up in this space, especially those on the severe end of the spectrum.

I would add that, as strange as it might sound, I see psychiatry and the mental health system as victims of (or at least profoundly constrained by) broader policy. Socioeconomics are much more central in my mind. Not just in the sense that structural disadvantages are profoundly implicated in the epidemiology of 

 (SMI) but also in the sense that what individuals are and what they can do with their lives is tied to socioeconomic capital, income (in)security, and the central roles of work and productivity in the context of socially valued roles. From the perspective of social justice, it is important to not just try to address problems at the level of psychopathology but also address the extra-individual ways in which macro-level systems shape individuals’ lives and do so in ways that are anything but just and equal in the case of individuals with SMI. So, a lot of my more recent work has focused on the ways in which deeper structural disadvantage, poverty, the American benefits system, and so on, influence what options are available, what services look like, and how lives unfold over the longer term.

The inclusion of consumer/survivor/ex-patient (c/s/x) perspectives in academic discourse in psychiatry has historically been a very neglected area. What are some of the consequences and implications of this absence? I am interested in the way this exclusion has affected psychiatry but also how it has affected those who have been excluded. It is common for me to encounter service users on Twitter who had unfavorable and negative experiences with psychiatric care (many of whom felt their voices were not heard), and as a result there is a lot of anger, pain, and frustration, sometimes to a point that individuals have lost all trust in the medical system.

And this is true across many different systems—criminal justice, child welfare, income-based social services, disability. At the broadest level, the problem is really the problem of social hierarchies, hierarchies of marginalization and exclusion, and, in some cases, incarceration and harm. Historically, there have been forced sterilizations as well as decades-long and sometimes life-long periods of (involuntary) commitment to asylums or state hospitals. There is collective pain, and also individual pain, distrust, and anger. The tragedy is that we have never seen the kind of dialogues and collaboration that this history demands. That is, there seems to me so much potential for deep listening and systemic rethinking or redesign work. Where policy is the real barrier, we need collaboration to change policy. That this has not happened only further undermines trust in the system and seeds ideological polarization. Since I am active both in user/survivor activist spaces as well as academic groups and lists, I often feel particularly painfully aware of the almost endless opportunities for dialogue, and the huge contribution that service users could make, but also the lack of meaningful opportunities to do so.

: “In the United States, the culture’s initial reaction to a person’s first psychotic episode, embedded most officially in a medical system that sees psychosis and schizophrenia as essentially biological, tends to cut the person off instantly from friends, social networks, work, and their sense of identity.”

This is something I have observed in the context of inpatient psychiatric hospitalizations for first episode psychosis. Psychiatric hospitalization is often a practical necessity since we as a society have failed to invest in other methods of psychiatric crisis management. However, I do recognize that it can be incredibly traumatic for some individuals on the one hand, while being therapeutic for others.

Psychiatric hospitals prioritize patient safety over comfort and autonomy, but an extreme emphasis on safety can sometimes be misplaced. The idea that we are fulfilling our duty to patients by offering them medications in a locked-door setting with bare-bones amenities reminds me of our attitudes toward children in the preattachment theory era when the consequences of maternal deprivation were seen as unimportant as long as the infant received physical care. Future generations may see our psychiatric hospitalization practices with a similar mix of curiosity and horror. What are your thoughts on this?

Involuntary hospitalization is something I have only recently started to study, although, as you say, it is an almost ubiquitous facet of pathways to and through early care for youth and young adults with first episode psychosis. A few years ago, I was awarded an internal grant to investigate the impact of involuntary hospitalization on youth across the diagnostic spectrum. We now have our first papers under review from the qualitative arm of this project. Overwhelmingly, within this sample, participants described inpatient environments as cold, dehumanizing, and punitive (with clearly negative impacts on participants’ reported willingness to trust future providers or disclose suicidal thoughts).

Perusing this data, I found the description of 

 as a kind of “punishment” most striking and most thought-provoking. Increasingly, the questions I have been asking myself, in part inspired by the legal socialization literature in criminology, concern the extent and ways in which these experiential entanglements of force and treatment, as well as perceived moralization in the paradoxical context of otherwise biomedicalized care, shape the development of system-related values, attitudes, and moral reasoning. I say paradoxical because one of the primary underlying motivations for physical health analogies has often been the putative mitigation of moral blame or culpability; and yet at the intersection of involuntary treatment and mental health, moral blame/moral discourse seemingly creeps right back in.

Of course, the existence and structuring of the average inpatient facility absolutely reflects the positionality and status of mental health challenges and crises in the United States. It is thus a kind of societal indictment. I also feel like this is pretty widely agreed upon. Few direct care clinicians I know are under any illusion about the therapeutic capacities of standard state- or county-funded inpatient facilities.

 What do you think of the early intervention in psychosis (EIP) services as they currently exist?

If we compare average to good early intervention in psychosis services to status quo care, the difference is stark. Meaning that so much of the time, under care as usual, young people will only have access to medication management and maybe, if they are lucky, some access to a therapist with at least minimal training in psychosis. EIP services have also really helped to elevate the relative clinical standing of what, for decades in the United States, has been an incredibly neglected sub-group. That is not to say services are perfect, nor that implementation has not been uneven; some states, like New York, have massively invested in training, technical assistance, and support, whereas other states have under-funded EIP programs, with little or no support. I do research on early psychosis around the country, and this really manifests in interviews with young people from well-supported, high quality services versus under-resourced, bare bones EIP services.

I would say that the real elephant in the room is what comes after early intervention—assuming there is access to well-implemented programs. What are young people with ongoing psychosis supposed to do following discharge? This is where the broader issue of how society, including employers and institutions of higher education, views psychosis and schizophrenia also rears its head. Even under the best of circumstances, clinical interventions can only go so far if societal structures and institutions do not accept (and ideally) embrace members of the broader community with disabilities and mental differences. Some of my teacher assistant’s work has tried to move in this direction. For example, with funding from the Substance Abuse and Mental Health Services Administration I developed 2 toolkits on supporting students with early psychosis in higher education. But we clearly have a long way to go.

 The role played by socioeconomic determinants—poverty, racial discrimination, stigmatization, domestic abuse, lack of education, unemployment, etc—in influencing the risk and course of schizophrenia has received relatively scarce research attention, although things are beginning to change. While a biogenetic conceptualization of schizophrenia has certainly downplayed social and structural factors with regards to poor outcomes, what is interesting is that some of the critical discourse has also shown a neglect of social and structural factors, and has instead been focused on trying to tie the poor outcomes to the use of 

As I see it, there have always been threads within the broader user/survivor movement that have focused on medications and treatment as central targets to the neglect of underlying structural determinants. This line of inquiry has consumed so much oxygen that it has ended up contributing to a neglect of structural determinants. I regularly talk to individuals who, for example, bring up the patently false claim that chronic psychosis would not exist were it not for antipsychotics. Ergo, this logic goes, all we have to do is remove medications from the equation, and we would massively reduce disability, chronicity, and so on. Similar logic seems to operate for Open Dialogue—the belief, that is, that if we simply withhold or massively reduce antipsychotics early in the disease, chronic psychosis will never develop.

What do I make of this all? It is frustrating in a whole lot of ways. The overwhelming focus on medications (or interventions like 

 associated with the minimization of medication use) ends up providing an almost perfect alibi for the kinds of conservative social welfare and benefits policies in place in the United States since the mid-1990s. Ultimately, what we are not doing is coming together, across identity and coalitional lines, to think deeply and creatively about the vast array of crisscrossing structural determinants, including income inequality, urban living conditions, limited class mobility, structural racism, and health care financing. Those are, from my perspective, the really major players.

Popular discourse on psychiatry, especially on online platforms and social media, is characterized by an extreme polarization. What do you think are some of the driving forces of this polarization? Why should we be worried about it, and what can be done?

I often think that if we knew each other as human beings rather than as caricatured identity groups (whether service users, activists, or psychiatrists) we would, or could, actually find a lot of common ground—build common ground, that is. Also, through dialogue, everyone learns to think more deeply, and with more nuance, about the issues at hand.

Another contributor, as I mentioned previously, are the individuals with various ideological axes to grind, a phenomenon we find on both ends of the ideological spectrum. These polarizing figures almost invariably seem to have little to no investment in recentering the views of those on the receiving end of public sector services, who, especially when it comes to schizophrenia and psychosis, are disproportionately poor, Black, and subject to myriad forms of disadvantage.

When I was a graduate student in Chicago, doing research in several of the city’s more notorious service ghettoes, I can tell you that the individuals I spoke to, interviewed, worked with for various projects, were not putting “decreased medication prescribing” on top of their priority list. It was housing, basic income, and access to food. I remember going on a home visit with an assertive community treatment team to accompany a young pregnant soon-to-be-mother to the grocery story. I remember feeling heartbroken that, 5 months before her baby was due, she was trying to build up a supply of diapers so that she would have enough when the baby was actually born. When push comes to shove, there is not even the slightest doubt in my mind that addressing these kinds of social conditions is the real priority when it comes to justice, as exemplified by the incredible poverty this young woman was experiencing and the underlying social disinvestment in individuals with significant psychiatric disabilities it represents.

: I would like to talk about the polarized state of online discourse on antipsychotics a little bit more. On one hand, we see folks insisting that everything is hunky-dory, and the very notion that the long-term use of antipsychotic medications could worsen functional outcomes even in some individuals is summarily dismissed. On the other hand, we see a sort of fanatic conviction that antipsychotics are toxic medications, that they in fact make schizophrenia worse, and the best thing we can do is to taper individuals off these medications.

Based on my understanding of the literature, the notion that there is a subset of individuals in whom long-term use may worsen outcomes strikes me as a plausible hypothesis, albeit one that needs to be confirmed by future research in the form of randomized controlled trials. What is clear is that individuals have very different experiences with these medications. For some, these medications can be incredibly therapeutic, offering relief and functional restoration, but for others, these medications may not do much or may cause harm. What is your take on this issue, and what are some of the pitfalls?

: I completely agree with you. I remember sitting in on a panel presentation with Lex Wunderink, MD, PhD, back in 2015 or so. (Wunderink has looked at 

 in individuals with first-episode psychosis with antipsychotic dose reduction/discontinuation).

 After the presentation, a very senior and influential schizophrenia researcher in the United States described Wunderink’s work as extremely important. He made basically the same points you do above but concluded that the big challenge is that we just do not know (and cannot currently identify) these sub-groups (individuals who will benefit vs those who will not, as well as in what ways and over what stretch of time). Obviously, this is not very helpful for either clients (or clinicians or family) stuck making decisions about medications in the here and now.

Also, in general, I think individuals tend to find areas of high uncertainty in any medical context highly stressful and discomforting. What I do think we need is true information and decision aids, ie, resources that lay out where the status of research literature is, resources that are transparent about the myriad unanswered questions we have and do not attempt to spin or sugar coat any of it. (I can honestly say I have never seen anything that I think actually does this—none of the medication-related shared decision-making tools or resources).

: As a psychiatric researcher and as someone with lived experience, you are a success story of service-user involvement in mental health research. What are the challenges you have experienced in navigating this dual role, especially with regards to simultaneously existing in the vastly different cultures of the psychiatric research community and the c/s/x community? How hard is it to do interdisciplinary work in an environment driven almost entirely by 

: Honestly, I will not consider myself successful, at least by the standards of the academy, until I have an R01 Notice of Award in hand. Otherwise, it is very challenging and quite painful a lot of the time—cognitive dissonance, code-switching. Back in 2017, the Alternatives conference, that big national gathering of user/survivor activists, happened to coincide in both time and place with the NIMH services conference. One of the days, I co-led a workshop on service user research involvement and priorities at Alternatives in the morning and presented at the NIMH venue in the afternoon. When I mentioned this to a handful of individuals at the latter, they had no idea the former was happening. I did not run into a single other university-based researcher at Alternatives. This is a kind of the structural example of what I see a lot—the opportunities to come together, but simultaneously the degree of separation, the lack of awareness. For me, these are the challenges of always feeling, uncomfortably, caught between 2 worlds.

Right now, a group of colleagues and I have a 

 on ways in which the field (administrators, senior PIs, funders) could better support a pipeline of mental health services— students, trainees, and researchers with experience of significant psychiatric disabilities and intersecting experiences of disadvantage. I would love for the research community to engage with, and dialogue about, the problems we call out and suggestions we raise there.

: How can psychiatry and psychology trainees acquire a better appreciation of the c/s/x perspectives? Is there any literature that you would like to recommend?

: A big part of me wants to completely side-step this question because while there are many powerful first-person accounts and narratives out there, I think that what is really needed is not more reading but direct engagement, dialogue, and conversation. Clinicians, as well as virtually all translational, clinical, and services researchers talk to service users all the time. However, this talk generally takes place in the form of the unidirectional provision of expert therapy or management. Instead, diverse service users need to be invited to the table as epistemic agents and interlocutors, rather than informants. All of us have to allow ourselves to be moved, emotionally as well as intellectually, in the course of this dialogue. We also need relationships, not one-off conversations, and relationships that can grow and evolve over time.

For anyone who does not know where to start, I am happy to make introductions, suggest listservs and forums where clinicians and researchers without existing relationships could start to make them. (My Twitter handle 

An extended version of this article appeared before print on October 8, 2020 with the title 

Phenomenology, Power, Polarization, and the Discourse on Psychosis: Nev Jones, PhD

is an interview series aimed to engage prominent critics within and outside the profession who have made meaningful criticisms of psychiatry and have offered constructive alternative perspectives to the current status quo. 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 

Drs Aftab and Jones have no relevant financial disclosures or conflicts of interest.

October 3, 2017. Updated November 26, 2018. Accessed September 20, 2020. 

https://psmag.com/magazine/the-touch-of-madness-mental-health-schizophrenia

Not what the textbooks describe: challenging clinical conventions about psychosis

DSM and the death of phenomenology in America: an example of unintended consequences

Beyond the sensory: Findings from an in-depth analysis of the phenomenology of “auditory hallucinations” in schizophrenia

“Did I push myself over the edge?”: complications of agency in psychosis onset and development

6. Jones N, Rosen C, Kamens S, Shattell M. 

“It was definitely a sexual kind of sensation”: sex, sexual identity, and gender in the phenomenology of psychosis

7. Wunderink L, Nieboer RM, Wiersma D, Sytema S, Nienhuis FJ. 

Recovery in remitted first-episode psychosis at 7 years of follow-up of an early dose reduction/discontinuation or maintenance treatment strategy: long-term follow-up of a 2-year randomized clinical trial

8. Jones N, Atterbury K, Byrne L, et al. 

Lived experience, research leadership and the transformation of mental health services: building a pipeline

Patient perspectives in academic discourse in psychiatry have historically been a neglected area. What are some of the consequences and implications of this absence? How has this affected both psychiatry and those who have been excluded? These questions and more are discussed.

Phenomenology, Power, Polarization, and Psychosis

A quick primer on nomenclature, issues to consider, and switching.

Psychiatric Treatment: Side Effects Basics

The US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Acadia Pharmaceuticals regarding their supplemental New Drug Application (sNDA) for pimavanserin for the treatment of hallucinations and delusions in patients with dementia-related psychosis (DRP). The FDA indicated the application cannot be approved in its current state.

The CRL cited the lack of substantial evidence of effectiveness needed for approval—specifically, lack of statistical significance in some of the subgroups of dementia and insufficient numbers of patients with less common forms of dementia.

“Acadia stands behind the robustly positive results from the pivotal Phase 3 HARMONY study and the prospectively agreed trial design and criteria for establishing efficacy in DRP. Over the entire course of the review, the Division did not raise any concerns regarding the agreed upon study design, including the issues raised in the CRL,” said Steve Davis, Chief Executive Officer of Acadia. “We will immediately request a Type A meeting to work with the FDA to address the CRL and determine an expeditious path forward for the approval of pimavanserin in DRP.”

Type A meetings are considered “immediately necessary for an otherwise stalled drug development program to proceed,” according to the 

Prior agreements with the FDA Division of Psychiatry regarding the pivotal phase 3 HARMONY study design concluded the intent was to target a broad DRP patient population analyzed as a single group. Prespecified requirements did not include statistical separation by dementia subgroups and minimum numbers of patients with specific subtypes.

The CRL also stated that the phase 2 Alzheimer disease psychosis study -019, a supportive study included in the sNDA filing, was inadequate and not well controlled.

 Reasoning for this belief included that it was a single center study, and there was no type I error control of secondary endpoints in which protocol deviations took place. Despite this, Acadia believes there is no impact on the positive results, nor on the study’s overall efficacy.

1. Acadia Pharmaceuticals. Acadia Pharmaceuticals receives Complete Response Letter from US FDA for supplemental New Drug Application for pimavanserin for the treatment of hallucinations and delusions associated with dementia-related psychosis. News release. April 5, 2021. 

https://www.businesswire.com/news/home/20210405005229/en/Acadia-Pharmaceuticals-Receives-Complete-Response-Letter-from-U.S.-FDA-for-Supplemental-New-Drug-Application-for-Pimavanserin-for-the-Treatment-of-Hallucinations-and-Delusions-Associated-with-Dementia-Related-Psychosis

2. US Food and Drug Administration. Type A Meetings. Accessed April 7, 2021. 

https://www.accessdata.fda.gov/cder/sb-navigate/topic3/topic3/da_01_03_0090.htm

3. Park B. FDA rejects pimavanserin sNDA for dementia-related psychosis. 

https://www.empr.com/home/news/drugs-in-the-pipeline/fda-rejects-pimavanserin-snda-for-dementia-related-psychosis/

CRL cites lack of substantial evidence of efficacy needed for approval. 

Dementia-Related Psychosis Treatment Receives Complete Response Letter

When do cognitive impairments emerge in patients with schizophrenia?

PsychQuiz: Cognition in Schizophrenia

In the years after World War II, there were no effective medicines for schizophrenia, bipolar disorder, or major depression. There were not even names for such things. The word 

 was first used at a medical meeting in 1956, 

 in 1953, but their acceptance was slow. Yet within the next 2 decades, all these types of medicines were developed. Most of drug discoveries occurred inadvertently, often with a chance observation by a physician or scientist who was looking for something else.

Many of the key figures in modern psychopharmacology were caught up in World War II in one way or another.

, who later initiated the use of chlorpromazine for psychoses, and John Cade, MD, who made the modern rediscovery of lithium for bipolar disorder, were military physicians. In both cases, one can see the influence of wartime experiences on their later work. Laborit was aboard a French destroyer struck by torpedoes during the evacuation of Dunkirk and was awarded a Military Cross for his actions during its sinking. After the development of chlorpromazine, he quickly suggested that it might be useful in managing stress in wounded soldiers on the battlefield (which proved to be an unsuccessful, even disastrous, endeavor). Cade volunteered for service in the Australian Army; he served in Singapore until he was captured and spent several years as a prisoner of the Japanese. While caring for fellow prisoners of war, he noticed their fluctuating levels of mental clarity, and wondered if this might be related to changing amounts of circulating substances, foreshadowing his later studies that led to lithium. 

Others crucial to the development of psychopharmacology were affected by the war in various ways. 

, who went on to discover meprobamate, the first modern tranquilizer, was a young physician in the Czechoslovak National Institute of Health who fled the Nazi occupation of his country. Arriving in Britain in 1939, he first worked providing medical care in refugee camps. Leo Sternbach, PhD, born in what is now Croatia, was an organic chemist who had experienced antisemitism firsthand in Poland. He was working for the Hoffman LaRoche Company in Basel when Germany invaded Greece and Yugoslavia in 1941. Facing an increasingly precarious situation, he fled through France and Portugal and came to the United States, where he later discovered the first benzodiazepine tranquilizer. The chemist 

, who worked on Britain’s secret atomic bomb research and served in the Home Guard when away from the laboratory, later applied some of his new-found techniques to develop the anesthetic halothane.

Still others lived through earlier wars. William A. Hammond, MD, who made observations with lithium in bipolar disorder in the 1870s, was Surgeon General of the Union Army during the American Civil War.

 Hans Berger, MD, served in the German cavalry in 1892 and was almost killed in a riding accident. His resulting curiosity about the workings of the nervous system led to the discovery of human electroencephalography. His story continued to include suffering at the hands of the Nazis, who took over his university in the 1930s. Constantin von Economo, MD, the Austrian psychiatrist and neurologist who described encephalitis lethargica and the role of hypothalamic structures in sleep and waking, was 

 Charles Sherrington, FRCP, FRCS, whose studies with Edgar Adrian, MD, clarified the processes of nerve cell communication, worked in a shell factory 13 hours a day during World War I, while Adrian took care of war casualties at St Bartholomew’s Hospital. Alexander Fleming, FRS, FRCS, whose later discovery of penicillin profoundly affected psychiatry by providing a treatment for tertiary syphilis, served in World War I, where his studies of evolving wounds led to 

Aside from psychopharmacology, the broader field of neuroscience also developed in the post-World War II years. Its founders also had pivotal experiences during wartime. Otto Loewi, PhD, whose experiments confirmed chemical transmission across synapses, was imprisoned by the Gestapo on the night of the German invasion of Austria. He was stripped of all his possessions, but was later allowed to emigrate on the condition that he transfer the funds from his Nobel Prize to a 

 An American self-taught scientist, Alfred Lee Loomis, DSc, JD, discovered the K-complex in the EEG and first classified the sleep stages, and then went on to play a crucial role in developing military radar in World War II.

 Sir Alan Lloyd Hodgkin’s experiences living in wartime Britain, and involvement in radar research impacted him in such a way that much later, at age 78, he felt the need to return to the war years in his last major work, 

Chance and Design: Reminiscences of Science in Peace and War

 As a medical student, Arvid Carlsson, MD, PhD, examined concentration camp prisoners who had been released to neutral Sweden. The encounter so impressed him that he talked about it at length in his Nobel Prize biography 56 years later. Starting in his 60s, Henri Laborit wrote extensively on the applications of neuroscience to aggression and violence. 

The remarkable thing about these stories is the variability of these experiences. Sometimes the war represented more of a hiatus in ongoing research, which was later resumed. In other cases, it led to displacement or imprisonment. Sometimes the result was devastating and culminated in suicide, while in other cases it was a stimulus leading to advances in research. It is a good reminder that, sadly, war is intimately involved in the human condition, and more specifically, that in order to understand the blossoming of neuroscience and psychopharmacology in the 1950s and 1960s, it is useful to take into account the wartime experiences of the founders.

is a professor of psychiatry and clinical pharmacology (ret) at the University of Chicago. His recent books include

Molecules, Madness, and Malaria: How Victorian Fabric Dyes Evolved into Modern Medicines for Mental Illness

Nepenthe’s Children: The History of the Discoveries of Medicines for Sleep and Anesthesia

Portions of this article are adapted from 

The Curious History of Medicines in Psychiatry

Trial by Fire: World War II and the Founders of Modern Neuroscience and Psychopharmacology

Molecules, Madness and Malaria: How Victorian Fabric Dyes Evolved into Modern Medicines for Mental Illness and Infectious Disease

The war experiences of physicians and scientists shaped their research agendas.

How the World Wars Affected Modern Neuropsychopharmacology

So, you think you have a pretty good handle on DSM-5—what the lay press loves to call, quite misleadingly, “Psychiatry’s Bible”? OK, maybe you know most of the criteria for the major categories of serious mental illness. No doubt, you are aware of serious problems with some aspects of DSM-5 (the 

, including the limited reliability and validity of many of its disorder categories.

 But how well do you understand the “deep structure” of DSM-5 as a diagnostic tool?

Just to get your adrenaline flowing, try taking this 2-minute quiz:

A. DSM-5 permits the clinician to make a mental disorder diagnosis simply by checking off the symptoms listed in a disorder’s diagnostic criteria.

B. To make a DSM-5 mental disorder diagnosis, the clinician need not assess the social, psychological and biological factors that may have contributed to the patient’s condition.

C. DSM-5 is an embodiment and expression of the “biomedical” model in psychiatry.

D. DSM-5 posits that mental disorders are discrete entities sharply distinguished both from “normality” and from each other.

Critics of psychiatric diagnosis often caricaturize the DSM process as the “Chinese Menu” approach. Thus, a professor of history and philosophy—in an article titled, “Forget talking, just fill a script: how modern psychiatry lost its mind”—

In clinical practice, DSM-III led to a “Chinese menu” approach to psychiatric diagnosis: a specific mental illness can be diagnosed if a sufficient number of boxes can be ticked. This is only of limited value in clinical practice.

Indeed, merely checking off boxes of symptoms (and signs) 

but that is not at all what DSM-5 calls for.

 As my colleague, Dr Mark Ruffalo, and I 

, the DSM-5 makes it crystal clear: Simply checking off symptoms 

cannot and does not constitute a psychiatric diagnosis—

The case formulation for any given patient must involve a careful clinical history and concise summary of the social, psychological and biological factors that may have contributed to developing a given mental disorder. 

Hence, it is not sufficient to simply check off the symptoms of the diagnostic criteria to make a mental disorder diagnosis 

, the case formulation “. . . is a core clinical skill that links assessment information and treatment planning. It is a hypothesis about the mechanisms that cause and maintain the problem. It answers the question, ‘Why is this person, having this type of problem, now?’”

In principle, the case formulation—and by extension, the final DSM diagnosis—requires medical knowledge, or at least access to medical consultation, in order to assess the “biological factors” that may have contributed to the patient’s problem. Finally, we should note that, in addition to meeting sign/symptom criteria for a mental disorder, virtually all the major 

 require evidence of “clinically significant distress or impairment in social, occupational or other important areas of functioning.” You cannot snag a DSM diagnosis merely by collecting a group of signs and symptoms. There must also be adverse consequences in the person’s life.

The DSM-5 Is “Biomedical”? Not So Much

It is clear from the aforementioned description of the case formulation that the DSM-5 explicitly uses a “biopsychosocial” approach to diagnosis. In addition, DSM-5 has extensive coverage of cultural issues, as they impinge on differential diagnosis. Excellent examples of the “case conceptualization” using a bio-psychosocial-cultural approach may be found in the text by Sperry and Sperry.

Nonetheless, some commentators—mainly critics of psychiatric nosology—have asserted that DSM-5 represents the “biomedical” model. For example, 1 paper 

Diagnostic and Statistical Manual of Mental Disorders

 . . . offers a biomedical framing of people’s experiences of distress and impairment, and despite decades of criticism, it remains the dominant approach.

These authors go on to argue that, “. . . a biomedical construction of ‘mental illness’ all too frequently fails to protect individuals from delegitimation and stigma.” That is a provocative claim worth examining but is beyond the scope of this essay. What is striking about the paper by these 2 psychologists is that the term “biomedical” is never fully defined. The authors do 

 the biomedical model is oriented “around the problems of the body . . . such as genetics or neurochemistry.”

If we take that rough formulation as a guide, it can be readily seen that—with a few exceptions—there is very little in DSM-5 that invokes “genetics” or “neurochemistry.” True, DSM-5’s discussion of 

 does reference abnormalities on chromosome 4; and other neurocognitive disorders, such as Lewy body disease, are linked to genetic abnormalities. But such references to specific genetic abnormalities are by far the exception, particularly for the more classically “psychiatric” disorders, such as schizophrenia and bipolar disorders. (We do find, under the rubric of “Risk and Prognostic Factors,” the statement that “Schizophrenia and bipolar disorder likely share a genetic origin . . .”

As far as I know, discussion of “neurochemistry” as a 

 in any of the common psychiatric disorders is entirely lacking in DSM-5. (So much for “chemical imbalances”). With only a few exceptions, DSM-5 avoids commitments regarding etiology. Indeed, the 

, “a diagnosis does not carry any necessary implications regarding the etiology or causes of the individual’s mental disorder. . .”

 One can see this as a serious deficiency in the DSM-5—but one cannot claim the 

endorses anything resembling neurochemical etiologies or “chemical imbalances” for the major mental disorders.

 that the DSM-5 “offers a biomedical framing of people’s experiences of distress and impairment.”

 Deacon, in a detailed review and critique, argues that “The biomedical model posits that mental disorders are brain diseases and emphasizes pharmacological treatment to target presumed biological abnormalities.”

 I do not contest that description, but nothing in Deacon’s analysis shows that DSM-5 is essentially “biomedical” in the sense he explicates.

Fuzzy Boundaries, Overlapping Symptoms, and Dimensions of Pathology

Another common claim is that DSM-5 is a strictly “categorical” framework that conceptualizes mental illness as a collection of discrete, diagnostically separable entities. As one paper puts it, “. . . the DSM-5 is a categorical system. Thus, individual disorders are regarded as discrete units—“you either have it, or you don't.”

 A related claim is that DSM-5 posits a clear and distinct separation between mental abnormality and “normal” mental or psychological states. 

In truth, neither claim is supported in the DSM-5 (

). On the contrary, the Introduction to the 

The results of numerous studies of comorbidity and disease transmission . . . make strong arguments for what many astute clinicians have long observed: the boundaries between many disorder “categories” are more fluid over the life course than DSM-IV recognized, and many symptoms assigned to a single disorder may occur, at varying levels of severity, in many other disorders. These findings mean that DSM . . . should accommodate ways to introduce dimensional approaches to mental disorders, including dimensions that cut across categories . . . Although some mental disorders may have well-defined boundaries around symptom clusters, scientific evidence now places many, if not most, disorders on a spectrum with closely related disorders that have shared symptoms, shared genetic and environmental risk factors, and possibly shared neural substates . . . 

In short, we have come to recognize that the boundaries between disorders are more porous than originally believed.

Furthermore, the DSM-5 does not argue for a hard and fast boundary between “normal” and “abnormal” states and conditions. On the contrary, it states:

The boundaries between normality and pathology vary across cultures for specific types of behaviors…Hence, the level at which an experience becomes problematic or pathological will differ. The judgment that a given behavior is abnormal and requires clinical attention depends on cultural norms that are internalized by the individual and applied by others around them, including family members and clinicians.

All this is not to say that psychiatric illnesses are merely “

” labels that have no corresponding physical or pathological referents in “the real world”—a thorny topic for another time.

 DSM-5 merely affirms what all good clinicians know: There are many 

 in the realm of psychopathology, often influenced by culture; and it is very doubtful that we can “carve Nature at its joints.”

 that democracy is the very worst form of government, except for all the others that have been tried.

 It is tempting to suggest, tongue slightly in cheek, that DSM-5 is by far the worst diagnostic framework psychiatry could have chosen—except for all the rest. To be sure, many different approaches to psychiatric diagnosis have been 

Personally, I favor a prototype-based diagnostic approach for every-day clinical work; and a parallel set of “research diagnostic criteria” for investigative purposes (

). “Prototype” diagnosis refers to the use of idealized models or archetypes of disease, rather than either “categorical” or “dimensional” methods of classification. 

 discuss and debate various diagnostic models in a wide-ranging colloquium.

It seems very clear that diagnosis is, and will always remain, a necessary part of clinical care, both in general medicine and psychiatry. When a patient presents with the complaint, “I hear threatening voices in my head,” we simply must

—a word whose etymology means, “knowing the difference between.” For example, we must know the difference between “threatening voices” stemming from combat-related trauma, on the one hand, versus schizophrenia or anti-NMDA receptor encephalitis

 on the other. Otherwise, our treatment is likely to be misguided.

No, whatever the lay press claims, DSM-5 is not “The Bible of psychiatry.’ It is not a sacred, eternal, and inviolable text, or even a very sophisticated diagnostic tool. John Talbott, MD, professor emeritus of psychiatry and former president of the 

A DSM-5 diagnosis requires a biopsychosocial case formulation—not just a symptom checklist.

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