research books on schizophrenia

The 20 Best Books about Schizophrenia

When I was first diagnosed with schizoaffective disorder bipolar type, I looked for the best books about schizophrenia to help me learn about what my new normal with my new diagnosis would look like. Ever a nerd, I researched the best schizophrenia books that would help me look at my condition from a spectrum of perspectives. This list contains 20 books on schizophrenia that reflect a diverse array of subjects and experiences, including books on understanding schizophrenia for families and loved ones and a multitude of memoirs about schizophrenia. It is my hope that it will be a resource for understanding schizophrenia that patients, family members, and mental health practitioners can use for help, healing, and hope.

You might also be interested in my list of the 20 best books about bipolar disorder …

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And now onto the best books about schizophrenia…

The center cannot hold by elyn r. saks.

Perhaps one of the most important books about schizophrenia, Elyn R. Saks’ The Center Cannot Hold: My Journey through Madness is undeniably a groundbreaking book in breaking the stigma of schizophrenia. Through relating her journey with schizophrenia, law professor Saks championed transparency while penning a riveting autobiography that cracked open the schizophrenia experience for all to see.

How to read it: Purchase The Center Cannot Hold on Amazon

Cognitive therapy of schizophrenia by david g. kingdon and douglas turkington.

When I was 18, I saw a student intern at the Penn Center for Cognitive Therapy for outpatient therapy. I was exhibiting some of the positive symptoms of schizophrenia (in particular, delusions), but they slipped through the cracks as I was treated primarily for depression and anxiety. The result was my cognitive therapy treatment wasn’t tailored to psychosis. Now, however, we have books like David G. Kingdon and Douglas Turkington’s Cognitive Therapy of Schizophrenia . This essential book is one of the best schizophrenia books for patients, allies, and mental health professionals alike. Finally we have a treatment option to alleviate schizophrenia symptoms beyond medication. Through chapters on topics like psychoeducation and normalization, intervening with delusions and hallucinations, and negative symptoms, this comprehensive book about understanding schizophrenia fills the gap in knowledge about how to treat schizophrenia with psychotherapy.

In short, this book gives me something I craved and needed so much when I was younger: hope.

How to read it: Purchase Cognitive Therapy of Schizophrenia on Amazon

The collected schizophrenias by esmé weijun wang.

While there’s plenty of writing about schizophrenia, there’s less out there about schizoaffective disorder, the condition I have. In The Collected Schizophrenias , Esmé Weijun Wang peels back the curtain on this comparably rare diagnosis. With essays spanning topics like fashion to being “high functioning” to specific delusions, like the Capgras delusion that your loved ones have been replaced by an identical imposter, The Collected Schizophrenias is an essential schizophrenia book and one of the best books on schizoaffective disorder.

How to read it: Purchase The Collected Schizophrenias on Amazon

The complete family guide to schizophrenia  by kim t. mueser and susan gingerich.

It can be hard to watch your loved one deal with schizophrenia, and, simultaneously, it’s equally hard to face this illness without the support of your family. Enter The Complete Family Guide to Schizophrenia by Kim T. Mueser, PhD, and Susan Gingerich, MSW. One of the best books for schizophrenia patients, this book covers topics like an overview of the illness, special issues for specific family members (like a patient’s mother, sister, or brother, etc.), preventing relapses, dealing with specific symptoms like delusions and hallucinations, and helping your loved one improve their quality of life. If you’re looking for a comprehensive guide to schizophrenia from a family standpoint, it doesn’t get much better than this book.

How to read it: Purchase The Complete Family Guide to Schizophrenia on Amazon

The day the voices stopped by ken steele.

Among the many best books on schizophrenias, the memoir The Day the Voices Stop is one of the oldest (published in 2001) and most highly regarded. This harrowing story follows Ken Steele’s lifelong struggle with schizophrenias, in particular command hallucinations and paranoid delusions, and eventual step towards healing with the help of psychiatric medicine. Steele’s vivid prose, written with Claire Berman, brings his nightmare and eventual recovery to life in this memoir that ranks among the best schizophrenia books.

How to read it: Purchase The Day the Voices Stopped on Amazon

Desperate remedies: psychiatry’s turbulent quest to cure mental illness by andrew scull.

There’s no history of schizophrenia without a history of psychiatry. And in Desperate Remedies , narrative medicine scholar Andrew Scull delivers a comprehensive history of the field of psychiatry. The author of the acclaimed history of mental illness, Madness in Civilization , Scull here has written an account of psychiatry that is equal parts readable, educational, rousing, fascinating, and challenging. Anyone who wants to learn more about schizophrenia within the context of the psychiatric field will want to pick this one up.

How to read it: Purchase Desperate Remedies on Amazon

The dialectical behavior therapy skills workbook for psychosis by maggie mullen, lcsw.

As a schizophrenic, I have always wished there were more therapy options for dealing with my illness, especially my psychosis symptoms. Sure, there’s medication, but how do you treat the condition outside meds? Enter The Dialectical Behavior Therapy Skills Workbook for Psychosis . Among the best books for schizophrenia patients, Maggie Mullen’s workbook fills the gap in therapy books about schizophrenia, offering the chance to develop skills of resilience, learn coping skills, and devise methods for dealing with psychosis outside medication. I love that this book is an interactive workbook you can go through at your own pace or with the assistance of a mental health professional. The Dialectical Behavior Therapy Skills Workbook for Psychosis is truly a beacon of hope in the treatment of psychosis.

How to read it: Purchase The Dialectical Behavior Therapy Skills Workbook for Psychosis on Amazon

Divided minds by pamela spiro wagner and carolyn s. spiro, m.d..

Many of the best books about schizophrenia are written by loved ones. That’s certainly the case with Divided Minds . Co-written by twin sisters Pamela Spiro Wagner and Carolyn S. Spiro, Divided Minds details the experience the two had while Pamela developed schizophrenia and Carolyn thrived. As Pamela’s condition deteriorated, Carolyn emerged as a medical student and, ultimately, a psychiatrist, but still the sisters remained close. Together and told in alternating voices, Pamela and Carolyn have written here a crucial book in the literature of memoirs about schizophrenia.

How to read it: Purchase Divided Minds on Amazon

The edge of every day by marin sardy.

If we’re talking about the best books about schizophrenia, Marin Sardy’s The Edge of Every Day definitely deserves a spot on that list. Sardy grew up with a schizophrenic mother in Anchorage, Alaska. Sardy’s mother refused treatment, leading to a challenging childhood for Sardy. Later, Sardy’s brother developed the same condition and ultimately died by suicide. In The Edge of Every Day, at the top of any list of the best schizophrenia books, Sardy collects her essays about the experience of being a loved one who bears witness to this untamable illness. Sardy’s voice is an important contribution to books about schizophrenia from the perspective of a family member.

How to read it: Purchase The Edge of Every Day on Amazon

Hidden valley road by robert kolker.

Robert Kolker’s Hidden Valley Road: Inside the Mind of an American Family was named one of the top five nonfiction books published in 2020 , and it’s not hard to see why. This engrossing read chronicles the devastating history of the Galvin family. Of their twelve children, six of Don and Mimi Galvin’s sons developed schizophrenia. What follows is a fascinating account of how the Galvins contributed to scientific research about the genetic nature of mental illness. The Galvins were among the first families that the National Institute of Mental Health studied. Although their lives were marked by the tragedy and hardship of mental illness, the Galvins persevered, and their history is presented in parallel with the evolving practices of psychiatry, psychotherapy, and psychopharmacology. This is definitely on the list of the best schizophrenia books.

How to read it: Purchase Hidden Valley Road on Amazon

A kind of mirraculas paradise  by sandy allen.

This interesting hybrid memoir deserves a spot on any list of the best books about schizophrenia. Sandy Allen’s eccentric Uncle Bob was allegedly “crazy” and had lived outside society in a series of mental institutions for parts of the ’60s and ’70s. But they didn’t really have a relationship. Until Uncle Bob sends Allen his autobiography in 2009, asking them to help bring it to publication. The result, A Kind of Mirraculas Paradise , is a hybrid memoir that includes Allen’s narrative and Uncle Bob’s autobiography as translated by Allen. This remarkable memoir is one of the most important schizophrenia books because it truly does tell Bob’s story to the world, an important record of narrative medicine about patient experiences.

How to read it: Purchase A Kind of Mirraculas Paradise on Amazon

Like crazy: life with my mother and her invisible friends by dan mathews.

When Dan Mathews watched his eccentric seventy-eight-year-old mother become unable to live independently, he crossed the country to stay with her in Virginia. While doing that, a trip to the emergency room reveals Mathews’ mother had lived her whole adult life as an undiagnosed schizophrenic. Uplifting and hopeful, count Like Crazy stands as ranking among the best memoirs about schizophrenia.

How to read it: Purchase Like Crazy on Amazon

Mind fixers: psychiatry’s troubled search for the biology of mental illness by anne harrington.

One of the ways we understand mental illness is through biology. But even biology has its limit in explaining how mental illness forms and how it gets treated. In Mind Fixers , Harvard history professor Anne Harrington explores the imperfect science of how psychiatry, neurology, and biology all fail to give us easy answers or even answer at all for the diagnosis and treatment of mental illness. Harrington dedicates a whole chapter to the complexities of the science behind schizophrenia. If you want to understand how to think about schizophrenia in biological terms, check out this book.

How to read it: Purchase Mind Fixers on Amazon

No one cares about crazy people by ron powers.

New York Times bestselling author Ron Powers delivers a searing indictment of the way the mentally ill are treated in America. The title of this book says it all: “No one cares about crazy people.” Powers has first-hand experience as his two sons both have schizophrenia. One died by suicide while the other lives but still struggles with his illness. While trying to be a good ally, Powers embarked on a journey down the mental health rabbit hole that ultimately lead to his realization of just how badly the system is stacked against the mentally ill and their loved ones. This is a challenging book to read because the results Powers finds are uneasy and unsettling, but this is book is a must have for anyone looking to understand schizophrenia.

How to read it: Purchase No One Cares About Crazy People on Amazon

The perfect other: a memoir of my sister by kyleigh leddy.

A newer title on this list of the best books about schizophrenia, The Perfect Other is a must read. Kait Leddy was overjoyed to have a younger sister, Kyleigh, the author of this memoir. But as Kait grew into an adolescent, cracks began to emerge: she was emotionally and physically volatile, her personality changed, and she began to lose her grip on reality. The result was a diagnosis of schizophrenia. Ultimately, Kyleigh lost her sister to schizophrenia. First, Kait went missing, and then she was seen on security cameras making her way to a bridge off which it’s concluded she jumped, though her body was never recovered. Memoirs about schizophrenia don’t get more raw and real than this.

How to read it: Purchase The Perfect Other on Amazon

The quiet room: a journey out of the torment of madness by lori schiller and amanda bennett.

The Quiet Room is a visceral reading experience as it relates Lori Schiller’s journey of madness. As an adolescent, Schiller had a seemingly perfect life. Six years later, she attempted suicide and then wandered the streets of New York speaking with invisible voices. And so began a lifelong battle with schizophrenia, one that took her through hospitals and half-way houses, while she struggled with co-morbid addiction. The Quiet Room is Schiller’s account of living with schizophrenia in a story that ends on a hopeful and uplifting note.

How to read it: Purchase The Quiet Room on Amazon

A road back from schizophrenia by arnhild lauveng.

Arnhild Lauveng’s captivating memoir A Road Back from Schizophrenia holds no punches and ranks among the best books about schizophrenia. In her autobiography, Lauveng offers a peek inside her experience with the illness, including the months or, in one case, a year inside psychiatric units and psychiatric hospitals, plus more about how it actually feels to have this condition. In zesty prose and unsparing detail, Lauveng offers a candid, honest look at living with schizophrenia.

How to read it: Purchase A Road Back from Schizophrenia on Amazon

Schizophrenia: a very short introduction by christopher frith and eve c. johnstone.

Schizophrenia is as complex as it is complicated. There’s a confusing set of symptoms that often lead to misdiagnosis, a host of conflicting medication and treatment options, and still many mysteries as the fields of medicine and science struggle to understand the origins and outcomes of schizophrenia. For an accessible, informative introduction on the disease, pick up Schizophrenia: A Very Short Introduction by Christopher Frith and Eve C. Johnstone, among the best books about schizophrenia. In barely more than 200 pages in a tiny book, the authors manage to demystify schizophrenia in this simple intro to this devastating mental illness.

How to read it: Purchase Schizophrenia: A Very Short Introduction on Amazon

Surviving schizophrenia: a family manual by e. fuller torrey, m.d..

Now in its seventh edition, Surviving Schizophrenia: A Family Manual remains one of the best books for schizophrenia patients. Understanding schizophrenia is easier when you have this book as your guide. For family members, allies, and loved ones, Surviving Schizophrenia helps those who care for a person with schizophrenia better comprehend the diagnosis, symptoms, and treatment of this oft-misunderstood illness. You’ll find this book covers topics like the causes of schizophrenia, the treatment of schizophrenia with meds and other options, and the onset, course, and prognosis of schizophrenia. Together, this book provides a roadmap through the stormy waters of schizophrenia and earns its stripes one of the great books about schizophrenia.

How to read it: Purchase Surviving Schizophrenia on Amazon

When the sun bursts: the enigma of schizophrenia by christopher bollas.

We’re ending this list of the best books about schizophrenia on a hopeful note. Acclaimed psychoanalyst Christopher Bollas argues that schizophrenia patients can be helped by gentler treatment than psychopharmacology, incarceration, dehumanization, and isolation that characterize so many schizophrenic experiences. Drawing on his fifty-year career, Bollas asserts that psychotherapy and, in particular, psychoanalysis, can help restore schizophrenic patients to stability. Given that this list of the best schizophrenia books has also featured cognitive therapy and dialectical behavioral therapy as treatment options, we have cause for hope that talk therapy and its variants can make a significant difference in the lives of those with schizophrenia and their family and loved ones.

How to read it: Purchase When the Sun Bursts on Amazon

Which of these best books about schizophrenia have you read leave a comment below., share this:.

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Sarah S. Davis is the founder of Broke by Books, a blog about her journey as a schizoaffective disorder bipolar type writer and reader. Sarah's writing about books has appeared on Book Riot, Electric Literature, Kirkus Reviews, BookRags, PsychCentral, and more. She has a BA in English from the University of Pennsylvania, a Master of Library and Information Science from Clarion University, and an MFA in Writing for Children and Young Adults from Vermont College of Fine Arts.

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Schizophrenia

Science and Practice

Edited by John C. Shershow

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ISBN 9780674791121

Publication date: 09/11/1978

Schizophrenia: Science and Practice brings together the work of many of today's most distinguished authorities in psychiatry. From diverse perspectives, these specialists review what is presently known—and unknown—about schizophrenia. The conceptual underpinnings of the diagnosis of schizophrenic illness, recent elaborations of psychosocial and developmental theories, current genetic and biochemical research, and traditional as well as newer treatment approaches are among the topics discussed in this unusually clear and lively account.

How effective are contemporary psychotherapeutic approaches to schizophrenia? What drug therapies are being used or proposed, and why? What about the treatment milieu and the difficult strategic questions surrounding the recent movement toward the “deinstitutionalization” of schizophrenic patients? Ultimately, should schizophrenia be defined as a toxic illness or as a way of life? In attempting to answer these and other questions, Dr. Shershow is joined by contributors Irwin Savodnik, Seymour Kety, Theodore Udz, Gerald Klerman, Ian Creese, Solomon Snyder, Leo Hollister, Jonathan Borus, Daniel Schwartz, and Loren Mosher, among others.

All the issues confronting psychiatry as a self-conscious discipline within contemporary medicine converge on the problem of schizophrenia. The important hope Schizophrenia: Science and Practice raises is that a fruitful pluralism among the variety of approaches to schizophrehia, and to psychiatric problems in general, can be sustained.

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• 6-1/8 x 9-1/4 inches
• Harvard University Press

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Schizophrenia and Psychotic Spectrum Disorders

Professor and Head, Department of Psychiatry

Professor In Residence, UCLA Department of Psychiatry and Biobehavioral Sciences

Assistant Professor of Psychiatry and Program Director, Psychiatry Residency

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Schizophrenia is a complex and heterogeneous disease of the brain, resulting from a complex interaction of innate susceptibility and environmental factors, involving multiple neurotransmitter systems and virtually all brain structures. As research in neurobiology, genetics, and epidemiology continues to progress at an astonishing rate, application of such knowledge may usher in newer and better interventions, ultimately reducing global burden and improving outcomes of schizophrenia. The primary focus of this volume is to present in readable form key topics in schizophrenia and other psychotic disorders, including a detailed review of the scientific literature on the pathophysiology underlying the disorder, symptoms, etiology, diagnostic approach, and treatments. People living with psychotic disorders have long been marginalized or misunderstood. This book is written with the goal of providing individuals in various disciplines, including trainees and established clinicians, a better understanding at multiple levels of one of the least understood psychiatric diagnoses. Improved understanding of the pathophysiology, phenomenology, intervention, and shaping of community and societal attitudes will lead to better outcomes for people with mental illnesses and their families.

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Handbook of Schizophrenia Spectrum Disorders, Volume I

Conceptual Issues and Neurobiological Advances

• © 2011
• Michael S. Ritsner 0

Sha'ar Menashe Mental Health Center, Hadera, Israel

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• Classification of the schizophrenia spectrum disorders - Neurobiological challenges - Phenotypic and endophenotypic presentations - Therapeutic approaches - Outcomes

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Biomarkers of Psychosis

Research Perspectives for Neuroimaging of Schizophrenia Spectrum Disorders

Schizophrenia

• Clinical presentations
• Endophenotype
• Neuroscience
• Schizophrenia spectrum disorders
• Treatment and outcomes

Table of contents (20 chapters)

Front matter, the schizophrenia construct after 100 years of challenges.

• Michael S. Ritsner, Irving I. Gottesman

Diagnosis and Classification of the Schizophrenia Spectrum Disorders

• Daniel Mamah, Deanna M. Barch

Toward a Multidimensional Continuum Model of Functional Psychoses for Research Purposes

Michael S. Ritsner

Irving Gottesman and the Schizophrenia Spectrum

• Aksel Bertelsen

Schizotypy: Reflections on the Bridge to Schizophrenia and Obstacles on the Road Ahead to Etiology and Pathogenesis

• Mark F. Lenzenweger

Autistic Spectrum Disorders and Schizophrenia

• Yael Dvir, Vishal Madaan, Lauren Yakutis, Jean A. Frazier, Daniel R. Wilson

One Hundred Years of Insanity: Genomic, Psychological, and Evolutionary Models of Autism in Relation to Schizophrenia

• Bernard J. Crespi

Quantifying the Dynamics of Central Systemic Degeneration in Schizophrenia

• Anca R. Rădulescu

Schizophrenia Has a High Heritability, but Where Are the Genes?

• Patrick P. McDonald, Shiva M. Singh

Changes in Gene Expression in Subjects with Schizophrenia Associated with Disease Progression

• Brian Dean, Andrew Gibbons, Elizabeth Scarr, Elizabeth A. Thomas

Amino Acids in Schizophrenia – Glycine, Serine and Arginine

• Glen B. Baker, Jaime E.C. Hallak, Alexandria F. Dilullo, Lisa Burback, Serdar M. Dursun

Developmental Consequences of Prenatal Exposure to Maternal Immune Activation

• Stefanie L. Bronson, Neil M. Richtand

Glutamatergic Neurotransmission Abnormalities and Schizophrenia

• Yogesh Dwivedi, Ghanshyam N. Pandey

Mathematical Models in Schizophrenia

• Zhen Qi, Gary W. Miller, Eberhard O. Voit

Methamphetamine-Associated Psychosis: A Model for Biomarker Discovery in Schizophrenia

• Chad A. Bousman, Stephen J. Glatt, Ian P. Everall, Ming T. Tsuang

What Does Proteomics Tell Us About Schizophrenia?

• Daniel Martins-de-Souza, Wagner F. Gattaz, Emmanuel Dias-Neto

The Role of 3α-Hydroxy-5α-Pregnan-20-One in Mediating the Development and/or Expression of Schizophrenia Spectrum Disorders: Findings in Rodents Models and Clinical Populations

• Cheryl A. Frye, Danielle C. Llaneza

Neural Substrates of Emotion Dysfunctions in Patients with Schizophrenia Spectrum Disorders

• Katharina D. Pauly, Ute Habel

Brain Morphological Abnormalities at the Onset of Schizophrenia and Other Psychotic Disorders: A Review of the Evidence

• Antonio Vita, Luca De Peri, Cesare Turrina, Emilio Sacchetti

Editors and Affiliations

Sha'ar menashe mental health center, hadera, israel, bibliographic information.

Book Title : Handbook of Schizophrenia Spectrum Disorders, Volume I

Book Subtitle : Conceptual Issues and Neurobiological Advances

Editors : Michael S. Ritsner

DOI : https://doi.org/10.1007/978-94-007-0837-2

Publisher : Springer Dordrecht

eBook Packages : Biomedical and Life Sciences , Biomedical and Life Sciences (R0)

Copyright Information : Springer Science+Business Media B.V. 2011

Hardcover ISBN : 978-94-007-0836-5 Published: 07 April 2011

Softcover ISBN : 978-94-017-8121-3 Published: 16 October 2014

eBook ISBN : 978-94-007-0837-2 Published: 06 April 2011

Edition Number : 1

Number of Pages : XVII, 494

Topics : Neurosciences , Neurobiology , Neurology , Neuropsychology

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Schizophrenia

Cognitive theory, research, and therapy, aaron t. beck , neil a. rector , neal stolar , and paul grant.

• description F rom Aaron T. Beck and colleagues, this is the definitive work on the cognitive model of schizophrenia and its treatment. The volume integrates cognitive-behavioral and biological knowledge into a comprehensive conceptual framework. It examines the origins, development, and maintenance of key symptom areas: delusions, hallucinations, negative symptoms, and formal thought disorder. Treatment chapters then offer concrete guidance for addressing each type of symptom, complete with case examples and session outlines. Anyone who treats or studies serious mental illness will find a new level of understanding together with theoretically and empirically grounded clinical techniques. -->
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• All titles by Paul Grant

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The Psychotherapy of Schizophrenia: A Review of the Evidence for Psychodynamic and Nonpsychodynamic Treatments

Following the discovery of chlorpromazine’s effectiveness as a treatment for schizophrenia in the 1950s, a gradual shift away from psychotherapeutic and toward biological methods of investigation has ensued. Nevertheless, psychological approaches to schizophrenia have a long history and continue to represent an important component of schizophrenia treatment. In the past 2 decades, there has been renewed interest in psychotherapy for schizophrenia among some clinicians and researchers. This article examines the current evidence for both psychodynamic and nonpsychodynamic (cognitive-behavioral, cognitive enhancement, and psychoeducational) therapies for schizophrenic illness. There is evidence to support the use of both types of therapies though these orientations generally differ in their views on the role of psychological factors in the etiology of schizophrenia. It is argued that a pluralistic or biopsychosocial model of schizophrenia is necessary to account for the complexity of the disease and to provide the most effective treatment.

Main Points

• Psychotherapy, often in conjunction with pharmacological therapy, represents an effective treatment for schizophrenia.
• Biological and psychological theories of schizophrenia are complementary, not antagonistic, approaches to the disease.
• There is evidence to support the use of both psychodynamic and nonpsychodynamic therapies for schizophrenia, though nonpsychodynamic treatments may be limited in their ability to address potentially underlying etiological factors.
• A pluralistic or biopsychosocial approach to schizophrenia is necessary to account for the complexity of the disease and to provide most effective treatment.

Introduction

Nearly 70 years after the discovery of the first neuroleptic drugs, schizophrenia continues to cause widespread burden and disability. Even with good pharmacological treatment, many patients continue to suffer and remain symptomatic throughout the duration of their lives. While research in neuroscience has yielded exciting information regarding the physiological aspects of the disease, these findings have not translated to improvements in treatment. 1 Indeed, the most effective medications for schizophrenia today are those discovered over a half-century ago. 2 Given this state of affairs, it seems wise to review the role of psychotherapy, psychiatry’s other core treatment, in the management of schizophrenic disease.

The psychotherapy of schizophrenia has a long history that predates the discovery of neuroleptics and electroconvulsive therapy for several decades. Freud believed that the schizophrenic was inaccessible to psychoanalysis but maintained that later modifications to psychoanalytic technique might render the patient treatable in psychotherapy. The psychiatrist Adolf Meyer, the first psychiatrist-in-chief at Johns Hopkins Hospital, developed a psychological theory of schizophrenia in the early 1900s. In the mid-20th century, a number of psychoanalysts, including, most notably, Harry Stack Sullivan, Silvano Arieti, and Harold Searles, studied schizophrenia from the psychodynamic perspective. Perhaps the most comprehensive text on the psychotherapy of schizophrenia Interpretation of Schizophrenia was published by Arieti 3 in 1974 and won the U.S. National Book Award in the Science category the following year. More recently, scholars from different psychotherapeutic modalities, such as cognitive behavioral therapy (CBT), have made their own contributions to the literature on schizophrenia, as the psychoanalytic tradition lives on.

This article seeks to provide a brief overview of several psychotherapies for schizophrenia (CBT, cognitive enhancement therapy (CET), psychoeducation, and psychodynamic psychotherapy) and review their evidence base. It is meant to inform the practicing clinician of the various therapeutic modalities to help select and guide treatment for the schizophrenia patient. It is not intended as an exhaustive review of any one of these psychotherapies; for this material, readers are directed to the authors cited in each section of this paper. Compared to other reviews of this topic, this paper seeks to adopt a more historically informed perspective, particularly on psychodynamic treatments for schizophrenia.

Nonpsychodynamic Therapies

Cognitive behavioral therapy was pioneered by Beck who in the early 1960s developed his cognitive therapy for the brief treatment of depression. Interestingly, Beck himself considered CBT to be a neo-Freudian therapy in the ego psychology school 4 though few modern CBT practitioners consider it as such. Since that time, CBT has been applied to a variety of psychiatric disorders, and much of Beck’s later work examined its role in the treatment of schizophrenia. 5 Early applications of CBT to schizophrenia focused mainly on the negative symptoms and emphasized behavioral strategies to improve social and independent-living skills, improve medication adherence, and provide other tools to solve day-to-day life challenges. 6

The positive symptoms of schizophrenia were initially not targeted by CBT interventions on the assumption that they are phenomenologically different from ordinary mental experiences and thus not amenable to the cognitive reframing strategies utilized in nonpsychotic illnesses. However, more recent modifications to CBT have opened the door to the use of these techniques for delusions and hallucinations, which are now conceptualized by CBT therapists as either intrusive thoughts—similar to those experienced in obsessive-compulsive disorder—or as misperceptions of reality. 6 This normalization of psychotic symptoms is said to help patients avoid negative thought loops and reframe problematic behaviors (such as social withdrawal) as compulsions based on a misinterpretation of outer threats. In 2021, the Beck Institute in Pennsylvania hosted its first-ever CBT for Schizophrenia workshop. 7 Other adaptations of CBT for schizophrenia have been advanced by researchers in the United Kingdom. 8

What is the evidence for CBT in schizophrenia? A 2001 meta-analysis of 7 controlled studies of cognitive treatment for chronic schizophrenia found a large mean effect size for the decrease in psychotic symptoms from pre- to posttreatment (0.65). 9 In the subset of 4 studies that followed patients for more than 6 months posttreatment, the mean effect size was even larger (0.93). It should be noted that in this study, cognitive treatments were defined as those targeting belief symptoms rather than information-processing abilities or behavior. A more recent British meta-analysis of 36 randomized controlled studies of cognitive behavioral therapy for psychosis (CBTp) concluded that while CBTp has a small therapeutic effect on functioning at the end-of-trial, it is not significant at follow-up. Furthermore, the authors noted that while CBTp produced a small benefit on distress, this was likely due to publication bias and became nonsignificant when adjusted. 10 Another review of 16 published articles including 12 randomized controlled trials found beneficial effects of CBT for both positive and general symptoms of medication-resistant psychosis, a finding that was also observed at follow-up. 11 A recent review of CBT for psychosis concluded that CBT can prevent the first episode of psychosis in ultra-high-risk patients and is effective in improving depression, self-esteem, and psychological well-being. Its use was associated with positive changes in thinking and mood, and sleep quality leading to improved everyday life. 12 Patients who underwent CBT had fewer hospitalizations with a higher number of voluntary hospitalizations as compared to patients with usual care, who underwent a higher number of involuntary hospitalizations. 12 Still, publication bias may account for some or all of these findings.

Given this mixed evidence for its effectiveness, CBT’s broad application for schizophrenia remains questionable. Substantial controversy has developed, particularly in the United Kingdom, surrounding its use. 13 It is noteworthy, however, that roughly 25%-50% of schizophrenia patients suffer from depression, 14 , 15 and the suicide risk in schizophrenia is high. The evidence for the use of CBT to treat depression is robust 16 and thus CBT may have utility in those schizophrenia patients with comorbid depressive illness. As with any psychotherapy, appropriate patient selection is paramount, and some schizophrenia patients may do quite well in CBT treatment.

In the mid-1990s, Gerard Hogarty, a social worker and professor of psychiatry at the University of Pittsburgh, developed personal therapy (PT) for schizophrenia, which combined psychoeducation with behavior therapy. 17 A few years later, Hogarty and Flesher 18 revised PT and developed a new treatment, CET, which aims to help schizophrenia patients improve subtle cognitive skills required for socialization. Whereas earlier therapies, including PT, utilize rote instruction to help prepare patients for social engagement, CET attempts to promote spontaneity and flexibility through structured but unrehearsed activities. 6 Cognitive enhancement therapy uses both computer-based exercises and group therapies. Computer-based exercises focus on improving cognitive skills, and group exercises seek to improve problem-solving skills and the ability to relate to others. The typical course of CET is 18 months.

A recent multisite randomized controlled trial of 102 patients with early schizophrenia found that CET improves both overall cognition and attention/vigilance in these patients, though CET did not outperform the control group, which received enriched supportive psychotherapy (EST), in social adjustment, as both the CET and supportive therapy groups had considerable improvements in this domain. 19 Patients were assessed at both 9 and 18 months, and the benefits of CET appeared to increase with treatment retention. A study of 58 patients with early-course schizophrenia (mean disease duration of about 3 years) comparing CET to EST found differential effects in favor of CET at 2 years in social cognition, cognitive style, and functional indications such as competitive employment, social functioning, global adjustment, and negative symptoms. 20 These effects were broadly maintained at 1-year posttreatment. 21 A 2022 analysis of 86 outpatients with early schizophrenia found that in addition to improving cognition, CET also significantly improves functional capacity as measured by the Brief UCSD Performance-Based Skills Assessment. 22 This suggests that CET’s effect on schizophrenia translates to real-world improvements in patients’ basic living skills.

Given these findings, CET appears to present a promising form of cognitive remediation for patients in the early stages of schizophrenic illness. Its adoption outside of university settings, however, has been limited. Much of the research on CET is conducted by a relatively small group of researchers at the University of Pittsburgh and a few other universities. As Brus et al 6 point out, most of the studies on CET have included patients with schizoaffective disorder in addition to schizophrenia, and they have excluded patients with comorbid substance use disorders and those who are medication nonadherent. Thus, CET’s broader utility in schizophrenia has not been fully studied. Additionally, CET does not target the positive symptoms of schizophrenia, which for certain patients (such as those with paranoid-type schizophrenia) comprise the most disabling feature of the disease.

Psychoeducation reflects another intervention for schizophrenia which has been considered a form of psychotherapy. The term was introduced in 1980 by the American researcher C.M. Anderson, also at the University of Pittsburgh, in the context of the treatment of schizophrenia. Generally, psychoeducation seeks to increase patients’ knowledge and understanding of their illness and its treatment. It is also frequently provided to the patient’s family members or caregivers. In the course of psychoeducation, schizophrenia patients are taught, for instance, that antipsychotic medication forms an integral part of treatment and can prevent relapse of symptoms. A large review of 5142 participants with schizophrenia (mostly psychiatric inpatients) concluded that psychoeducation significantly reduces relapse, readmission, and length of hospital stay, in addition to promoting medication compliance. 23 Evidence also suggests that participants receiving psychoeducation are more likely to be satisfied with mental health services and have improved quality of life. 23 Another recent study found that psychoeducation resulted in consistent improvement in psychotic symptoms as well as treatment adherence in patients treated pharmacologically with long-acting, second-generation antipsychotics. 24 In this study, patients given psychoeducation also evidenced improvements in several metabolic and physiological measures, indicating that psychoeducation can help reduce severity of medication side effects and provide benefits beyond a reduction in psychiatric symptomatology.

Other nonpsychodynamic therapies for schizophrenia include family therapy, humanistic and existential psychotherapy, vocational rehabilitation, social skills training, metacognitive training, and social cognition therapy, and among others. While this article does not review these forms of treatment, their exclusion here should not necessarily be interpreted as implying a lack of efficacy or the unimportance of these treatments.

Nonpsychodynamic therapies like CBT , CET, and psychoeducation may each play a role in the management of schizophrenia patients, yet they are treatments designed to target only the symptoms of the disorder; there is little evidence to suggest that any of these treatments deal with the psychological factors which serve to engender the disorder from a biopsychosocial perspective. Thus, nonpsychodynamic therapies may be limited in their ability to address underlying etiological factors which play a role in the development of the disease.

Psychodynamic Therapy

The history of psychodynamic treatment of schizophrenia is over 100 years old. 25 Freud was originally pessimistic about the possibility of treating schizophrenia (then called “dementia praecox”) with psychoanalysis as he believed the patient was incapable of developing a transference. In time, Freud modified his views and insisted that the schizophrenia patient required a more active and confrontational method than utilized in classical psychoanalysis. Early pioneers in psychoanalytic work with schizophrenia patients include Paul Federn, Karl Abraham, Poul Bjerre, Alfred Alder, Adolf Meyer, and among others. In these first few decades, the psychoanalytic treatment of schizophrenia was met with uncritical acceptance. We must remember, however, that many of the patients treated by these analysts came from well-to-do social classes and were thus able to afford such intensive treatment. They were also likely more ambulatory than the average schizophrenia patient. 25

The mid-20th century saw great excitement in the possibility of psychoanalysis to prevent and cure schizophrenia. The first director of the U.S. National Institute of Mental Health (NIMH), practicing psychoanalyst Robert Felix, explicitly forbade government expenditures on biological investigation, insisting that advances in psychoanalysis would soon solve the problem of schizophrenia and, in fact, all mental diseases. 26 Psychoanalytic hospitals, such as Chestnut Lodge and the Menninger Clinic, opened as centers for the psychoanalytic treatment of schizophrenia. Leaders in this area during the 1940s and 1950s included Frieda Fromm-Reichmann, Melanie Klein, and Harry Stack Sullivan. It was perhaps Sullivan who was the most influential of these theorists in the mid-century, his ideas laying the groundwork for much of the later developments in the psychotherapy of schizophrenia and in psychoanalysis more generally (such as the so-called “relational turn”). His 1962 book Schizophrenia as a Human Process provided a primarily psychological, as opposed to biological, conception of the root causes of schizophrenia. 27

In the following few decades, 2 analysts stand out as the preeminent figures in the psychotherapy of schizophrenia: Silvano Arieti and Harold Searles. Searles is noted for his emphasis on countertransference in work with these patients. Arieti, whose clinical approach emphasized emotional warmth and basic trust, provided a psychologically informed, pluralistic approach to the disorder, his work serving as a precursor to the field’s later adoption of Engel’s biopsychosocial model. 28

A thorough review of the psychodynamic approach to schizophrenia is outside the scope of this paper, and theories within psychoanalysis are vast and sometimes contradictory when it comes to work with these patients. In fact, there is no single “psychodynamic therapy” for schizophrenia but perhaps dozens or even hundreds. Still, psychodynamic approaches to schizophrenic illness tend to share some common features. These include a focus on the early environment of the patient, in particular, the causative role of anxiety; the meaning and symbolism of psychotic symptoms; an emphasis on the relationship between patient and therapist, including transference and countertranference reactions; the etiological role of the psychological factors (as opposed to the view that psychological dysfunction is merely caused by the disorder; see section on the pluralistic approach below); and a long-term (or longer-term) approach to psychotherapy.

Central to the psychodynamic perspective is the belief that in the mental world, as in the physical world, events are determined by the events which precede them; nothing in the psychological realm can be said to happen by chance. This is true even for those mental experiences that seem so foreign to most of us: psychotic symptoms. Despite the often bizarre and illogical nature of these symptoms, a careful psychodynamic investigation can reveal their idiosyncratic meaning and function.

I will share a few brief examples to illustrate a psychodynamic interpretation of schizophrenia.

In paranoid-type schizophrenia, the patient is engrossed in a delusional theme which places them at the center of some dreaded situation or plot. Frequently, the patient experiences auditory hallucinations which align with the delusional ideas; they hear others speaking negatively or critically about them. In these cases, the patient projects to the external world his hostile feelings toward himself; no longer does the patient accuse himself, now the accusations come from others.

The patient who experiences olfactory hallucinations of a foul odor emanating from his body has concretized his unconscious belief that he is a bad or rotten person; as unpleasant as it is to smell awful, it is much more tolerable than to believe that one is awful.

A man who believes that others are controlling his thoughts experiences a reactivation and concretization of the way he once felt that his parents were controlling or trying to direct his life and way of thinking.

In cases of catatonic schizophrenia, the patient may assume a statuesque position for long periods of time. Overwhelmed by the intense anxiety which accompanies responsibility, the patient becomes “frozen in time,” shielded from the potential destructiveness of his own actions.

In each of the above examples, the schizophrenic symptoms are interpreted as defense mechanisms that serve a psychological function for the individual, namely, to alleviate an unbearable anxiety rooted in intense self-criticism. Nevertheless, the symptoms eventually come at a much greater cost to the patient than whatever benefit is had, and it is for this reason that they are pathological.

What is the evidence for the psychodynamic treatment of schizophrenia? The literature is filled with anecdotes and case reports highlighting successful treatment of individual patients. Perhaps the best-known example of such writing is the semi-autobiographical novel of one of Fromm-Reichmann’s patients, the 1964 bestseller I Never Promised You a Rose Garden. 29 One of my own patients, a young man with paranoid-type schizophrenia whom I have been treating for 5 years, wrote the following about our psychodynamically oriented psychotherapy:

The work didn’t click for me until years in. Every psychotic experience was always preceded by a split second shift in my emotional state. Over time, I was able to feel this window open up … and my experiences slowly dissipated. I still experience psychotic symptoms but at a much less frequent rate. Every session a new layer of what has happened to me is unraveled through therapy. Almost every time a link has been discovered, I subsequently experience less symptoms.

These types of case reports notwithstanding, there exists a dearth of high-quality, modern research on the psychodynamic psychotherapy of schizophrenia. There are likely several reasons for this, and one does not have to be too cynical to recognize them. Certainly, the advent of the neuroleptic medications ushered in a new era in psychiatry, and the influence of the insurance industry led to a prioritization of manualized, short-term therapies and more symptom-focused approaches to treatment. As the old saying goes, “He who pays the piper picks the tune.” Additionally, most psychoanalysts work with schizophrenia patients in private practice settings and do not hold full-time faculty positions at universities where they conduct research on psychotherapy. In fact, as Shedler 30 has repeatedly pointed out, the researchers who study psychotherapy tend to know the least about psychotherapy as a clinical discipline; many of them have not seen a patient in treatment for decades. Yet, psychoanalysis as a discipline shares the blame in all of this too. For decades, psychoanalysis was an insular community that was disinterested in demonstrating the efficacy of its treatments via contemporary research. (Analysis is by its very nature an intensely private endeavor that is ill-suited for modern research designs.) And it is true that the efficacy of psychoanalytic treatments for schizophrenia was likely exaggerated by most mid-century analysts, who refused to consider the influence of biological and genetic factors and the effectiveness of antipsychotic drugs.

The largest study of psychotherapy for schizophrenia to date was the Boston Psychotherapy Study, conducted in the 1980s. 31 Done at a time when the influence of biological therapies was growing, the study compared exploratory, insight-oriented psychotherapy (EIO), which employed psychodynamic techniques, with reality-adaptive supportive psychotherapy (RAS), which focused on here-and-now problem-solving. It was conducted at 3 sites and involved 95 patients and 81 experienced psychotherapists, with a 2-year follow-up, albeit with a significant dropout rate. The main finding was that while patients improved with psychotherapy, there was no difference between therapy groups on most measures. Consistent with the primary focus of each therapy, RAS showed an advantage in reducing hospital readmissions, improving work-role performance, and maintaining household responsibilities, while EIO showed an advantage in improved ego functioning and cognition. A subsequent analysis revealed a significant relationship between the therapist’s skillful dynamic exploration and better outcomes. As Garrett writes, “An enormous amount of thought, time, and resources went into this study, an effort not soon to be repeated in the current climate of research funding which favors neuroscience.” 32

So, where does that leave psychodynamic psychotherapy for schizophrenia? After treating hundreds of schizophrenia patients with year-long psychodynamic treatment, it is my view that such therapy is at least as important as biological therapies in the management of the disease and that psychodynamic treatments address certain core psychotic problems that cannot be addressed by either pharmacotherapy or nonpsychodynamic forms of therapy. Undoubtedly, further empirical research is needed to confirm these observations, and some patients are simply not suitable for psychodynamic treatment (such as those who have failed previous psychodynamic treatments and those in the latter stages of the disease). Yet, this belief in the fundamental role of psychodynamic therapies is shared by many analysts and analytic therapists who have worked with schizophrenics in the past half-century. As the expert pharmacologist and ethicist Louis Lasagna noted in 1975, most of our knowledge about the disease and its treatment comes “not from controlled trials, but from natural observations by smart physicians using their past knowledge and experience as control.” 33 Certainly the same is true for psychotherapy.

Although psychodynamic therapy for schizophrenia has been an understudied subject, empirical support for many of the concepts central to psychodynamic work with schizophrenia has been established in the past 2 decades. This includes confirmation of the importance of early attachment in the later development of psychotic disorder; 34 , 35 the meaning of psychotic symptoms and their relationship to adverse environmental experiences; 36 , 37 and the relationship between biology and psychology in individual susceptibility to schizophrenia. 38 Thus, there exists evidence in addition to clinician and patient experience to support the use of psychodynamic interventions in schizophrenia.

A Pluralistic Approach to Schizophrenia

Since the early 1980s, the predominant theoretical model in academic American psychiatry has been Engel’s biopsychosocial model, which considers biological, psychological, and social factors in the etiology of mental disorder. This was predated by Adolf Meyer’s psychobiology in the early 20th century and, as noted above, Arieti’s pluralistic approach in the mid-to-late 20th century. Nevertheless, much of the research and scholarly activity on schizophrenia over the course of the past 40 years has been strictly biological in nature. Modern textbooks on schizophrenia may only include short passages on psychosocial approaches which are usually limited to brief, manualized therapies, and psychosocial rehabilitation. Discussions of the psychological aspects of schizophrenia often consider these problems as consequences rather than as causes of the disease. Thus, much of the modern psychiatric literature on schizophrenia lacks the pluralism that is found in writings from the past century.

For instance, in the second edition of their now-classic textbook Perspectives of Psychiatry, McHugh and Slavney 39 write, “Schizophrenic symptoms are psychological events without explanation, and without is the operant word” [emphasis in original]. 39 They add that these symptoms are “mental phenomena in which no glimmer of psychological cause and effect can be perceived.” 39 The authors write as if they are unaware of the long and enduring history of psychologically informed approaches to schizophrenia though this is a gratuitous assumption. In many circles in the 1990s, schizophrenia was declared a brain disease by fiat , not because psychological or psychodynamic theories were proven false.

In his 1956 paper “The Possibility of Psychosomatic Involvement of the Central Nervous System in Schizophrenia,” Arieti 40 describes a nuanced biopsychosocial theory of the etiology of the disease:

The impact of the psychological conflicts is too much to bear for a part of the central nervous system which is already genetically vulnerable. At times it may be too much to bear even if such hereditary predisposition does not exist. On the other hand, the hereditary vulnerability alone, without the psychogenetic factors, would not be enough to engender the disorder.

Here we see the view that the psychological factors are etiological ones and that schizophrenia is caused by a complex interplay between biology and the environment and not solely by neurobiological mechanisms. It is this perspective upon which most psychodynamic therapies for schizophrenia are based, whereas some nonpsychodynamic therapies either reject such etiological theories or remain neutral on the matter of cause.

While it is certainly true that psychotherapy alone cannot cure schizophrenia, it is equally true that for many patients, psychotherapy is the key to finding meaning, reclaiming a sense of personal satisfaction, and improving the patient’s general life situation. Writing beautifully in 1974, Arieti 41 describes the goal of psychotherapy for schizophrenia:

To summarize, with many patients who receive intensive and prolonged psychotherapy we reach levels of integration and self-fulfillment that are far superior to those prevailing before the patient became psychotic. As I have said elsewhere, this does not mean that all the troubles of the patient will be over, even after successful psychotherapy. We must repeat once again the famous words of Frieda Fromm-Reichmann that we cannot promise a rose garden. It would be utopian to believe that the promise of life is a life comparable to a rose garden, utopian for the patient and utopian for us, who want to be his peers. But I think it is not utopian to promise to the patient what we promise to ourselves, his peers, sooner or later in life: to have our own little garden.

As clinicians and researchers, we must remain open to exploring all vistas when it comes to schizophrenia and work toward bridging equally plausible theories from both the biological and psychosocial perspectives. At times this may mean revisiting the work of those theorists who came before us. They were, after all, seeing the same types of patients with the same kinds of illnesses, often in work conditions much better suited for a thorough psychological investigation of the patient’s mind and its workings. In the end, no reductionism but rather informed pluralism must prevail in the understanding and treatment of this severe disease.

Despite increased interest in the genetic and biological studies of schizophrenia in recent decades, psychotherapy continues to play an important role in the treatment of this major psychosis. Schizophrenia is a complex illness that is best conceptualized utilizing a pluralistic or biopsychosocial framework. In any given case, biological, psychological, and social forces are at interplay and thus a comprehensive approach to treatment is needed to produce the best result. While antipsychotic medications are effective in reducing the positive symptoms of schizophrenia, treatment response is often incomplete and many patients continue to suffer indefinitely. These medications also often carry significant side effects. The psychotherapeutic approach, which is best considered as a complement to pharmacotherapy, has a long history for schizophrenia, beginning with the psychoanalysts in the early 20th century. Since then, advancements in psychoanalytic thinking as well as contributions by authors from other theoretical orientations have broadened our understanding of the disorder. There is evidence to support the use of both psychodynamic and nonpsychodynamic therapies in the treatment of schizophrenia, though these approaches generally conflict in their views on the role of psychological factors in the etiology of the disease. While there is a dearth of randomized controlled data on the use of psychodynamic approaches, there exists a world literature spanning many decades supporting their effectiveness in schizophrenia.

Funding Statement

The author declared that this study has received no financial support.

Peer-review: Externally peer-reviewed.

Declaration of Interests: The author has no conflict of interest to declare.

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Understanding Schizophrenia: A Practical Guide for Patients, Families, and Health Care Professionals

Written by two physicians with decades of clinical and research experience in the field, this volume helps readers face schizophrenia by understanding what it is and how it is managed. Schizophrenia is a devastating illness that affects more than two million Americans. Written to help anyone who is faced with managing schizophrenia, whether as a patient, friend, or family member, this accessible book is an ideal first stop for practical, up-to-date information. It includes an overview of schizophrenic disorder and provides answers to common questions that arise at different phases of the illness. This brief and to-the-point guide focuses on dealing with many aspects of schizophrenia―complying with treatment, managing crises, being a caregiver, communicating with the care team, and coping skills. The book also provides practical approaches to common issues, such as financial support, housing, employment, interacting with the legal system, stress management, socialization, and negative emotions. Included are useful forms, lists, and a comprehensive collection of resources to access help and information. The goal of this book is to assist patients and their loved ones to effectively face schizophrenia, achieve maximal recovery, and enjoy a good quality of life.

• ISBN-10 1440831505
• ISBN-13 978-1440831508
• Publisher Praeger
• Publication date September 15, 2015
• Language English
• Dimensions 6.14 x 0.56 x 9.21 inches
• Print length 224 pages
• See all details

Editorial Reviews

“This is a resource to keep at hand―to guide people affected by schizophrenia to be proactive managers of the illness and to consult when there is a change or when facing bureaucratic or personal challenges. Summing Up: Highly recommended. Professionals and general readers.” ― Choice “Knowledge concerning the various aspects of schizophrenia has been developing rapidly recently. Keeping up with this multifaceted progress can be a challenging task. Understanding Schizophrenia goes a long way toward producing a much-needed book in this vein. The authors have skillfully integrated relevant research findings and translated them into plain English for meaningful communication to persons with the illness and their family members . . . . From the beginning, the authors make clear that in many cases persons with a diagnosis of schizophrenia can lead a normal life, depending on appropriate treatment and the seriousness of the condition . . . they reaffirm that the traditional Kraepelinian view―that one cannot recover from schizophrenia―is no longer accepted, at least not for everyone with this disorder. . . . The volume provides practical, up-to-date information that should be helpful to anyone affected by, or otherwise interested in, schizophrenia. . . . The book is easy to read and conveys a plethora of valuable suggestions and helpful guidance for persons living with schizophrenia, their family members, and others who want to learn more about this condition, which has so often been portrayed as a mysterious and devastating disorder from which few were able to recover.” ― Psychiatric Services

"The essential guide to schizophrenia for patients, their families, and care teams. Clear, concise, and thoroughly understandable information about what schizophrenia is, what it means, and what can be done about it. I wish I'd had it by my side years ago!"

Randye Kaye, author of Ben Behind His Voices: One Family's Journey from the Chaos of Schizophrenia to Hope

About the Author

Ravinder Reddy , MD, is adjunct professor of psychiatry at the University of Pittsburgh School of Medicine. He has been involved in psychiatric education for more than 25 years. Matcheri S. Keshavan , MD, FRCPC, MRCPsych, is Stanley Cobb Professor and vice chair for public psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School.

Product details

• Publisher ‏ : ‎ Praeger (September 15, 2015)
• Language ‏ : ‎ English
• Hardcover ‏ : ‎ 224 pages
• ISBN-10 ‏ : ‎ 1440831505
• ISBN-13 ‏ : ‎ 978-1440831508
• Item Weight ‏ : ‎ 1.6 pounds
• Dimensions ‏ : ‎ 6.14 x 0.56 x 9.21 inches
• #270 in Schizophrenia (Books)
• #308 in Psychopathology
• #1,745 in Medical Psychology Pathologies

About the author

Ravinder reddy.

Ravinder (Ravi) Reddy, MD, Fellow of the Royal Asiatic Society, is a psychiatrist, author and teacher.

During his academic career, he primarily worked with patients suffering from schizophrenia as well as the homeless. For several years, he directed the training of a new generation of psychiatrists.

Alongside his medical career, Ravi has been deeply interested in many aspects of Indian art. Over the course of four decades, he has studied Kushan numismatics, medieval Shaivaite sculpture, early maps depicting the Indian subcontinent, and arms and armour of the region. For him, Indic arms and armour reflect a unique convergence of the martial culture, the high arts, history, and technical mastery of metal work. His new project, forthcoming as a book in a year or two, is examining sacred imagery on functional objects and in the arts.

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Tanya Luhrmann's new book examines the root causes of schizophrenia

Schizophrenia has long puzzled researchers in the fields of psychiatric medicine and anthropology. Why is it that the rates of developing schizophrenia—long the poster child for the biomedical model of psychiatric illness—are low in some countries and higher in others? And why do migrants to Western countries find that they are at higher risk for this disease after they arrive? T. M. Luhrmann and Jocelyn Marrow argue that the root causes of schizophrenia are not only biological, but also sociocultural.

This book gives an intimate, personal account of those living with serious psychotic disorder in the United States, India, Africa, and Southeast Asia. It introduces the notion that social defeat—the physical or symbolic defeat of one person by another—is a core mechanism in the increased risk for psychotic illness. Furthermore, “care-as-usual” treatment as it occurs in the United States actually increases the likelihood of social defeat, while “care-as-usual” treatment in a country like India diminishes it.

EDITORIAL article

Editorial: reviews in psychiatry 2023: schizophrenia.

• 1 University Hospital of Cagliari, Cagliari, Italy
• 2 Institute of Applied Physiology, Faculty of Medicine, University of Ulm, Ulm, Germany
• 3 Department of Psychology, University of Córdoba, Córdoba, Spain

Editorial on the Research Topic Reviews in psychiatry 2023: schizophrenia

Schizophrenia is a severe psychiatric disorder that imposes a considerable burden on patients, their families, and society as a whole ( 1 ). The fact that the burden of schizophrenia is compounded by the insufficient efficacy of available treatment options has motivated a wide range of clinical and pre-clinical research endeavors. The contributions to this Research Topic represent this diversity of research and thereby mirror the complexity of the disorder itself. Schizophrenia is a nosological entity with a very heterogeneous spectrum of deficits. These are categorically identified as positive, negative, and cognitive symptoms ( 2 ). Moreover, recent discoveries regarding inherent biomarkers ( 3 ) and neurodevelopmental disease progression ( 4 ) increasingly suggest possible overlap with other psychiatric disorders, such as bipolar disorder ( 5 – 7 ). This overlap ranges from genetic ( 5 ) and environmental ( 6 , 7 ) risk factors to pathophysiological mechanisms and symptoms ( 8 , 9 ). Recognition of symptomatologic patterns and familiarities between disorders may provide a more precise diagnostic framing and better management of clinical aspects. It is important to identify factors that can support the differential diagnosis and allow the most appropriate treatment for Schizophrenia patients who represent nosographic clusters of considerable complexity ( 10 ). Thus, an overview of both quantitative and qualitative data on clinical characteristics and treatment outcomes may elucidate the patterns and mechanisms of Schizophrenia pathogenesis and its modifiability ( 11 , 12 ). In this regard, the reviews included in this Research Topic allow for an in-depth reflection on several aspects of mental pathology in general and highlight possible future directions of scientific advancement ( 13 ).

Several reviews have examined the effectiveness of non-pharmacological treatment options for Schizophrenia. For example, in parallel with standard psychosocial and pharmacological treatment, the use of virtual reality offers new solutions that can lead to appreciable results in various functional and symptomatic domains. The review by Holopainen et al. on the efficacy of immersive extended reality (XR) interventions on different symptom domains of Schizophrenia spectrum disorders showed that treatment gamification allows for greater patient engagement in therapy, harnessing the motivation of novelty represented by this virtuous technology. Furthermore, unlike drug treatment which is often associated with many side effects and stigma, this therapeutic approach is believed to be devoid of such drawbacks and likely to provide a favorable end-user experience and greater overall adherence to the treatment. Similarly, Cao and Zhou described the effects of computerized cognitive remediation therapy (CCRT) on mental time travel in patients with Schizophrenia. Their review highlighted how this treatment may prove to be a relatively simple, inexpensive and effective way to improve symptoms.

In contrast, Tyssedalu et al. highlighted how interventions with dogs for adults diagnosed with Schizophrenia can improve their quality of life, well-being, and several positive and negative symptoms, including features associated with the severity of psychosis. However, the results of some of the reviewed studies should be interpreted with caution.

In a systematic review conducted on the treatment effects of adjunctive group music therapy in inpatients with chronic Schizophrenia, Lam et al. found that, as an add-on to standard treatment, this intervention can produce an additional improvement. Several of the 13 randomized controlled trials included in the review found beneficial effects at the level of positive symptoms - particularly auditory hallucinations -, cognitive function – especially attention - and/or negative symptoms. For the latter, improvements in avolition, social withdrawal, anhedonia, and self-care were particularly evident. At the level of subjective perception, patients also reported improvements in energy, mood, anxiety, relaxation, and quality of life.

Exploring the possibility of alternative pharmacological treatments, Bortoletto et al. reviewed the evidence for the role of the endogenous lipid palmitoylethanolamide (PEA) in psychosis. Although it does not activate the cannabinoid receptors CB1 and CB2 directly, it shares several other targets with classical endocannabinoids and enhances the availability of the latter ( entourage effect ). As it has been suggested that disruption of the endocannabinoid (eCB) system may be implicated in the etiopathogenesis of psychosis, PEA may represent a better-tolerated antipsychotic agent acting through the eCB system. In addition to its well-known analgesic properties, PEA also exerts neuroprotective and anti-inflammatory effects that may ameliorate the pathological development of Schizophrenia. Evidence suggests that PEA may specifically improve manic and negative symptoms, including apathy. Importantly, no serious adverse effects were reported in any of the human studies reviewed, suggesting a very beneficial safety profile for PEA.

Several other reviews have investigated the symptomatology of schizophrenia and related disorders. Motut et al. conducted a meta-analysis that revealed a significant correlation between social cognition and metacognition in subjects with Schizophrenia Spectrum Disorder. They were able to identify this association in various cognitive and social domains particularly those related to theory of mind, attribution and emotion processing, while no correlations emerged with indicators of cognitive intuition, self-reflexivity, or understanding others’ minds. Beyond symptomatology, the authors also noted that metacognitive training and insight therapy represent non-pharmacological interventions that may benefit social cognition and possibly other cognitive functions in individuals with Schizophrenia Spectrum Disorders.

In addition, Di Luzio et al. reviewed the clinical features and comorbidities of very early onset Schizophrenia (VEOS) and reported that it appears to be very similar to early-onset (EOS) and adult-onset forms of Schizophrenia (AOS). However, VEOS has some peculiar characteristics, especially a greater presence of visual hallucinations and more common resistance to conventional treatment in female patients. Moreover, men and women are equally likely to develop VEOS, which differs from the usual 1.5 times higher prevalence of general Schizophrenia in men. Guiral et al. , in turn, emphasized the critical role of neuropsychological dimensions related to alterations in verbal self-monitoring of language production in Schizophrenia patients. A general consensus emerged from the review that language processing and associated mechanisms of verbal self-monitoring are not deemed secondary, but rather fundamental to the disorder. A particularly clear link with emotional and cognitive dimensions, such as perception, is reported, and accompanying neurophysiological measurements have revealed the involvement of frontotemporal networks and regions such as the insula, amygdala, putamen and cingulate cortex. Based on these findings the authors suggested the development of neuropsychological techniques and tests for a better diagnosis and treatment of Schizophrenia.

Similarly, Calciu et al. investigated the psychotic phenomenon of dissociation and its relationship to recovery from psychosis. The authors reported that dissociative psychotic experiences are a very complex phenomenon that involves multiple mechanisms and influences recovery, whereas this field appears to be clearly understudied.

Finally, Hui et al. reviewed studies comparing Delusional Disorder (DD) and Schizophrenia and reported that, overall, no differences emerge between age-matched and non-age-matched features. However, compared to Schizophrenia, DD is associated with generally better outcomes in terms of psychopathology and functioning.

In summary, the reviews included in this Research Topic highlight a number of aspects and draw synoptic conclusions that are not easily identifiable in individual research articles given the considerable methodological and conceptual diversity in Schizophrenia research. For example, more confidence could be gained regarding the effectiveness of alternative or adjunct treatment approaches, such as VR- or animal-based therapy, computerized cognitive remediation therapy, or music therapy. Furthermore, the summaries of current evidence provided for rather understudied conditions in the Schizophrenia-related spectrum such as VEOS, dissociation, verbal self-monitoring, metacognition, and Delusional Disorder point to future research needs and directions. Overall, the reviews underscore that an approach to complex mental pathologies like Schizophrenia or the psychotic spectrum ( 14 ) based solely on isolated symptomatic aspects appears to be suboptimal. Therapies using multiple technologies and integrated approaches promise that treatment can be more comprehensive and humanely respectful. It is also evident that the integration of multiple aspects can stimulate the scientific community to develop new strands of clinical, basic and technological research with a view to achieving an increasingly optimal outcome in terms of satisfactory symptom management and improved quality of life.

Author contributions

MT: Conceptualization, Formal analysis, Methodology, Writing – original draft, Writing – review & editing. DK: Writing – review & editing. TS-G: Writing – review & editing.

Acknowledgments

The authors thank all contributing authors who have made this Research Topic a reference for the field.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

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4. Zhao NO, Topolski N, Tusconi M, Salarda EM, Busby CW, Lima CNNC, et al. Blood-brain barrier dysfunction in bipolar disorder: Molecular mechanisms and clinical implications. Brain Behav Immun - Health . (2022) 21:100441. doi: 10.1016/j.bbih.2022.100441

5. Carta MG, Kalcev G, Scano A, Pinna S, Gonzalez CIA, Nardi AE, et al. Screening, genetic variants, and bipolar disorders: can useful hypotheses arise from the sum of partial failures? Clin Pract . (2023) 13:853–62. doi: 10.3390/clinpract13040077

6. Carta MG, Kalcev G, Scano A, Primavera D, Orrù G, Gureye O, et al. Is bipolar disorder the consequence of a genetic weakness or not having correctly used a potential adaptive condition? Brain Sci . (2023) 13:16. doi: 10.3390/brainsci13010016

7. Carta MG, Kalcev G, Fornaro M, Pinna S, Gonzalez CIA, Nardi AE, et al. Does screening for bipolar disorders identify a “Dysregulation of mood, energy, and social rhythms syndrome” (DYMERS)? A heuristic working hypothesis. J Clin Med . (2023) 12:5162. doi: 10.3390/jcm12155162

8. Perra A, Galetti A, Zaccheddu R, Locci A, Piludu F, Preti A, et al. A recovery-oriented program for people with bipolar disorder through virtual reality-based cognitive remediation: results of a feasibility randomized clinical trial. J Clin Med . (2023) 12:2142. doi: 10.3390/jcm12062142

9. Kalcev G, Scano A, Orrù G, Primavera D, Cossu G, Nardi AE, et al. Is a Genetic Variant associated with Bipolar Disorder Frequent in People without Bipolar Disorder but with Characteristics of Hyperactivity and Novelty Seeking? Clin Pract Epidemiol Ment Health CP EMH . (2023) 19:e174501792303280. doi: 10.2174/17450179-v19-e230419-2022-53

10. Carta MG, Fornaro M, Primavera D, Nardi AE, Karam E. Dysregulation of mood, energy, and social rhythms syndrome (DYMERS): A working hypothesis. J Public Health Res . (2024) 13:22799036241248022. doi: 10.1177/22799036241248022

11. Anticevic A, Cole MW, Repovš G, Savic A, Driesen NR, Yang G, et al. Connectivity, pharmacology, and computation: toward a mechanistic understanding of neural system dysfunction in schizophrenia. Front Psychiatry . (2013) 4:169. doi: 10.3389/fpsyt.2013.00169

12. Guan F, Ni T, Zhu W, Williams LK, Cui L-B, Li M, et al. Integrative omics of schizophrenia: from genetic determinants to clinical classification and risk prediction. Mol Psychiatry . (2022) 27:113–26. doi: 10.1038/s41380-021-01201-2

13. Spathopoulou A, Sauerwein GA, Marteau V, Podlesnic M, Lindlbauer T, Kipura T, et al. Integrative metabolomics-genomics analysis identifies key networks in a stem cell-based model of schizophrenia. Mol Psychiatry . (2024), 1–13. doi: 10.1038/s41380-024-02568-8

14. Tusconi M, Dursun SM. Editorial: Further findings in the role of inflammation in the etiology and treatment of schizophrenia. Front Psychiatry . (2024) 15:1349568. doi: 10.3389/fpsyt.2024.1349568

Keywords: schizophrenia, biomarkers, therapeutic targets, systematic reviews, psychosocial functioning, psychological therapy, symptom domains, pharmacological therapy

Citation: Tusconi M, Kätzel D and Sánchez-Gutiérrez T (2024) Editorial: Reviews in psychiatry 2023: schizophrenia. Front. Psychiatry 15:1444818. doi: 10.3389/fpsyt.2024.1444818

Received: 06 June 2024; Accepted: 18 June 2024; Published: 04 July 2024.

Edited and Reviewed by:

Copyright © 2024 Tusconi, Kätzel and Sánchez-Gutiérrez. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Massimo Tusconi, [email protected] ; Dennis Kätzel, [email protected] ; Teresa Sánchez-Gutiérrez, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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Rounds in the General Hospital

Treatment-Resistant Schizophrenia: Evaluation and Management

Carol S. Lim, MD, MPH; Abigail L. Donovan, MD; Chirag M. Vyas, MBBS, MPH; Nicholas O. Daneshvari, MD; Desta S. Lissanu, MD; and Theodore A. Stern, MD

Published: July 2, 2024

Lessons Learned at the Interface of Medicine and Psychiatry

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.

Prim Care Companion CNS Disord 2024;26(4):23f03692

Author affiliations are listed at the end of this article.

H ave you been unclear about how treatment resistant schizophrenia (TRS) is defined? Have you been uncertain about how to evaluate a patient with a chronic psychotic illness? Have you struggled over which treatments you should consider when treating someone with TRS? If you have, the following case vignette and discussion should prove useful.

CASE VIGNETTE

Ms C, a 35-year-old woman, first became psychotic with auditory hallucinations and paranoia (ie, her neighbors were constantly communicating with her and trying to break into her house) during her sophomore year of college; she had also been using cannabis frequently. Despite stopping cannabis for more than 3 months, her psychosis persisted. She was initially treated with lurasidone (as she preferred a weight-neutral agent), but even with doses over 90 mg/d for 6 weeks, there was no improvement in her psychotic symptoms. She was switched to risperidone, and the dose was titrated to 3 mg at bedtime. Her hallucinations and paranoia subsided but failed to remit. When she felt somewhat better, she stopped her medications for several months; this led to a relapse and a lengthy hospitalization. Given her medication nonadherence as an inpatient, she was trialed on oral Invega and transitioned to a monthly long acting injectable (Invega Sustenna 234 mg) to ensure adherence. Even after getting monthly injections without interruption for 3 months, her symptoms persisted. Her outpatient psychiatrist started olanzapine (and titrated it to 20 mg/d) and discontinued the injections. Even with consistent adherence to olanzapine (20 mg/d) for 2 months, her symptoms showed only minimal responsiveness.

Ms C was diagnosed with TRS for having failed 2 nonclozapine antipsychotic trials (with adequate dose, duration, and adherence). She was encouraged to start clozapine, but due to the burden of regular blood work monitoring and her fear of weight gain, she did not agree to a clozapine trial for 6 months. Her executive function deteriorated, which resulted in her losing her job. Paranoia led her to call 9-1-1 multiple times each day to report her neighbors’ suspicious behaviors. She trespassed on her neighbor’s property and received a restraining order. Ultimately, she was hospitalized involuntarily.

What Is TRS?

Schizophrenia is a chronic, progressive psychiatric disorder characterized by symptoms that include hallucinations, delusions, disorganization, impaired motivation, deficits in self-expression, and cognitive impairment. 1 Unfortunately, a subset of patients with schizophrenia do not respond to first-line treatments, which necessitates more complex clinical decision-making to limit morbidity and mortality.

In 2017, the Treatment Response and Resistance in Psychosis (TRRIP) Working Group published criteria for treatment resistance based on an international expert consensus. 2 This group defined TRS by having at least moderate symptom severity and functional impairment due to schizophrenia, with an inadequate response to 2 or more antipsychotic medication trials. Validated scales should be used to measure and confirm symptom severity (eg, the Brief Psychiatric Rating Scale [BPRS]) 3 and functional impairment (eg, the Social and Occupational Functioning Assessment Scale). 4 Each antipsychotic trial requires a sufficient dose (equivalent to at least 600 mg of chlorpromazine daily), duration (a minimum of 6 weeks), and patient adherence (at least 80% of prescribed doses taken). Of note, the above criteria represent minimal TRRIP benchmarks for diagnosing TRS; optimal TRRIP criteria also include prospective monitoring of symptom severity via a scale that confirms less than 20% symptom decrease over the antipsychotic course and confirmation of antipsychotic adherence via 2 or more plasma levels and trialing at least 1 long-acting injectable.

About one-third of patients with schizophrenia meet criteria for TRS, a high proportion of whom are treatment resistant from the onset of their psychotic illness (ie, primary TRS). 5 Given that the duration of untreated psychosis and repeated psychotic episodes increases treatment resistance, identification of TRS and early intervention are necessary to improve treatment outcomes. 6

What Looks Like TRS But Is Not?

The differential diagnosis of TRS involves considering other key psychiatric conditions, such as schizoaffective disorder or bipolar disorder with psychotic features. Distinguishing between TRS and other psychiatric conditions can be challenging, as they share psychotic symptoms. Table 1 outlines the key features of TRS, schizoaffective disorder, and bipolar disorder with psychotic features.

What Does the Evaluation of TRS Involve?

The evaluation of TRS begins with a thorough review of the patient’s psychiatric and treatment history. All nonpsychiatric causes of psychosis should be ruled out before concluding that a person has TRS. Moreover, the patient should meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision, criteria for schizophrenia. 7 In addition, consensus criteria suggest that evidence-based, validated symptom rating scales, such as the Positive and Negative Syndrome Scale (PANSS), 8 the BPRS, 3 the Scale for the Assessment of Negative Symptoms (SANS), 9 or the Scale for the Assessment of Positive Symptoms (SAPS), 10 should be used to quantify current overall, positive, and negative symptom severity. Current symptom severity should be moderate (or higher) in at least 2 areas (eg, auditory hallucinations, delusions, and negative symptoms) or severe in 1 area. 2

The evaluator must also determine that the patient has failed 2 or more antipsychotic trials that were adequate regarding the dose, duration, and adherence. 2 To consider an antipsychotic trial as having failed, a patient’s symptoms should have improved by less than 20% or they must have continued to experience moderate symptoms in 2 or more areas or have severe symptoms in 1 area 2 while taking an antipsychotic with adequate dose, duration, and adherence. An adequate duration is typically considered to be at least 6 weeks on a therapeutic dose (ie, at least 600-mg equivalents of chlorpromazine/day). 2 Adequate adherence is defined as at least 80% of prescribed doses taken, as confirmed by at least 2 sources, including pill counts, dispensing chart review, or patient or caregiver report. 2 In addition, antipsychotic drug levels should be monitored at least once during the medication trial. 2 Multiple sources of information (including from the patient and their family and from medical records) may be used to determine the efficacy of a prior response. In addition, other factors (including active substance use or untreated medical problems) that may contribute to ongoing psychotic symptoms must also be ruled out.

What Kinds of Biological, Psychological, and Social Interventions Can Help to Manage TRS?

Patients with TRS should be offered a clozapine trial. It is the only US Food and Drug Administration (FDA)–approved antipsychotic medication for TRS, and it has superior efficacy when compared to all other antipsychotics. 11 For patients with TRS, there is limited benefit obtained with use of other nonclozapine antipsychotics. 12 The initial serum level target for clozapine is a trough level >250 ng/mL. 2 If there is an insufficient response at this level, the dose should be increased to achieve a level >350 ng/mL. 2 Monitoring of serum levels is crucial since individual factors (such as sex and cigarette smoking) can affect serum levels and therefore treatment response. 2 A clozapine trial that lasts at least 3 months is required once therapeutic levels have been achieved. 2

Some patients fail to respond adequately to clozapine. On the population level, augmentation with a second antipsychotic or another adjunctive medication is unlikely to be helpful, and there is no clear support for any augmentation strategy over another. 13,14

Use of nonpharmacologic treatments should also be considered as adjunctive treatments. Electroconvulsive therapy (ECT) may be beneficial for people with TRS who have not achieved an adequate treatment response with clozapine. Up to 50% of patients with TRS improve with ECT. 15 In addition, cognitive-behavioral therapy for psychosis has demonstrated moderate efficacy for patients with TRS. 16 Transcranial magnetic stimulation (TMS) may offer some improvement in symptoms for people with medication-resistant auditory verbal hallucinations, 17 although much of the literature has demonstrated mixed results regarding positive symptoms. 18 Similarly, the literature regarding the effect of TMS on negative symptoms is also mixed. 18,19 Finally, research has not demonstrated benefits associated with rehabilitative treatment in improving social functioning, such as increasing patients’ participation in activities in TRS. 20

When Should Other Medications, Neuromodulatory Techniques, or Surgical Approaches Be Considered When Someone Is Thought to Have TRS?

An adequate trial of clozapine should be established before trying augmentation strategies. A clozapine trial should last at least 3–4 months with at least an 80% adherence rate and with a serum clozapine level >350 ng/mL. 21 The clozapine dose should be increased to at least 450 ng/mL for nonresponders; however, neither upper levels for therapeutic benefits nor toxicity have been established, and the dose can be raised, as tolerated, if ongoing benefit is noted. Therapeutic drug monitoring is critical to confirm an adequate dosage and adherence because some patients may be rapid metabolizers of clozapine, drug-drug interactions may arise, and tobacco use can decrease clozapine levels. 22 Nevertheless, about half of those with TRS have clozapine-resistant schizophrenia (ie, they show minimal or no symptomatic response to clozapine and require adjunctive treatments).

After optimizing the clozapine dosage, several strategies can be considered for persistent symptoms. ECT is the evidence-based treatment for clozapine resistant schizophrenia. Symptom improvement of 40%–50% has been noted with ECT. 15 However, ECT is not always immediately available, and patients often do not agree with its use; in the interim, pharmacologic augmentation strategies are often tried for patients who continue to take clozapine. Although there were promising trials of clozapine augmentation with less invasive repetitive TMS, a meta-analysis found no evidence of effectiveness for psychotic symptoms. 21 In terms of medications, adjunctive aripiprazole can reduce psychotic symptoms, mitigate metabolic side effects of clozapine, improve mood and negative symptoms, and serve as an augmentation strategy to lower the risk of psychiatric rehospitalization compared to clozapine monotherapy. 23 The data regarding the effectiveness of mood stabilizers as augmentation therapy are mixed and contradictory. Among the most widely studied mood stabilizers for augmenting clozapine are lamotrigine, topiramate, lithium, and valproic acid; however, further research is needed to reach definitive conclusions. Valproic acid appears to have a calming effect on patients experiencing acute psychosis accompanied by hostility, but its long-term effect is less clear. 24

How Can Family Members of Those With TRS Become Better Prepared to Help Their Loved Ones?

Navigating the complexities of coping with TRS poses significant challenges for both affected individuals and their familial support networks. To better prepare their loved ones who are struggling with TRS, family members should acquire knowledge about TRS. Accompanying affected individuals during a routine health care appointment allows family members to gain critical insights into the fundamental aspects of TRS, its symptomatic manifestations, and the spectrum of available treatment modalities. Research also suggests that most families of patients with TRS report that they have received inadequate information regarding the early warning signs of relapse, side effects of medications, and ways that they can cope with violent behaviors. 25 To address these issues, during interactions with health care professionals, family members should discuss how to recognize early signs of psychotic decompensation, which can lead to timely intervention and support. In addition, families should be equipped with de-escalation strategies to handle potential crises effectively, particularly when patients struggle with paranoia or engage in fear-related physical protective responses. There are often local chapters of nationwide organizations, such as the National Alliance on Mental Illness (NAMI), that can help patients and their families (ie, Family to Family programs help family members best support patients). It is imperative for families to identify nonpolice emergency response resources within their community to ensure appropriate assistance during crises, minimizing the risk of misinterpretation and escalation in potentially volatile situations. This collaborative approach empowers family members to initiate timely interventions, thereby mitigating the impact of crises and improving the overall quality of life for their loved ones.

In addition, effective communication plays a crucial role in supporting individuals who are grappling with TRS. It would be advantageous for family members to enhance their communication skills; this may help to establish a secure environment that encourages open and honest conversation between loved ones and their family members and allows affected individuals to express their thoughts and emotions without restriction.

While assisting loved ones who are struggling with TRS, family members should prioritize their own mental health and well-being. For example, research suggests that persistent positive symptoms and frequent relapses associated with TRS has been linked to a perceived burden, which results in feeling overwhelmed with a lack of relief and takes a toll on the emotional and physical health of caregivers. 26 Participating in support groups or seeking guidance from mental health professionals enables family members to develop invaluable coping strategies. This approach serves not only to prevent the worsening of mental and emotional health but also to help sustain resilience among family members, which is required for supporting a loved one with TRS over an extended period.

Case Vignette: What Happened to Ms C?

Eventually, Ms C agreed to a clozapine trial. Therapeutic drug monitoring of clozapine blood levels was used to avoid both toxic and subtherapeutic levels, and the dose was titrated to a target of 350 ng/mL (with a clozapine dose of 400 mg/d). However, she continued to struggle with paranoia. She benefited from raising the clozapine dose to 500 mg/d, which led to a serum clozapine level of 450 ng/mL. However, this dose/level made her too sedated and constipated, and she was drooling excessively; these symptoms were managed with laxatives and glycopyrrolate, respectively. However, severe fatigue prevented her from returning to work, and her clozapine dose was reduced to 400 mg/d and aripiprazole was added, which improved her psychotic symptoms, energy level, and mood and also mitigated further weight gain.

Schizophrenia is a chronic, progressive psychiatric disorder characterized by hallucinations, delusions, disorganization, impaired motivation, deficits in self expression, and cognitive impairment. TRS is defined by having at least moderate symptom severity and functional impairment due to schizophrenia, with an inadequate response to 2 or more antipsychotic medication trials. Assessment and monitoring should be accomplished with the aid of validated symptom rating scales (such as the PANSS, the BPRS, the SANS, or the SAPS) to quantify current overall, positive, and negative symptom severity. When individuals have TRS, they should be offered a clozapine trial; it is the only FDA-approved antipsychotic medication for TRS, and it has superior efficacy when compared to all other antipsychotics. In addition, cognitive-behavioral therapy for psychosis has demonstrated moderate efficacy for patients with TRS. Moreover, effective communication plays a crucial role in supporting individuals who are grappling with TRS.

Article Information

Published Online: July 2, 2024. https://doi.org/10.4088/PCC.23f03692 © 2024 Physicians Postgraduate Press, Inc. Submitted: December 26, 2023; accepted March 12, 2024. To Cite: Lim CS, Donovan AL, Vyas CM, et al. Treatment-resistant schizophrenia: evaluation and management. Prim Care Companion CNS Disord . 2024;26(4):23f03692. Author Affiliations: Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts (all authors); Harvard Medical School, Boston, Massachusetts (all authors). Corresponding Author: Carol S. Lim, MD, MPH, Department of Psychiatry, Massachusetts General Hospital, 151 Merrimac St, 4th Floor, Boston, MA 02114 ( [email protected] ). Drs Lim, Donovan, Vyas, Daneshvari, and Lissanu are co-first authors. Relevant Financial Disclosures: Dr Lim reports receiving research grants from Karuna, Merck, and Neurocrine; consultant honoraria from Karuna; and medical honoraria from MDedge and Hatherleigh. Dr Vyas has received research support from Nestlé-Purina Petcare Company, Mars Edge, and American Foundation for Suicide Prevention. The other authors report no conflicts with any product mentioned or concept discussed in this article and have no disclosures. Funding/Support: None.

Clinical Points

• Treatment-resistant schizophrenia is defined by having at least moderate symptom severity and functional impairment due to schizophrenia, with an inadequate response to 2 or more antipsychotic medication trials.
• Validated scales should be used to measure and confirm symptom severity.
• Each antipsychotic trial requires a dose that is equivalent to ≥600 mg/d of chlorpromazine, for a minimum of 6 weeks, and with at least 80% of prescribed doses taken.
• Therapeutic drug monitoring is critical to confirm an adequate dosage and adherence because some patients may be rapid metabolizers of clozapine, drug-drug interactions may arise, and tobacco use can decrease clozapine levels.
• After optimizing the clozapine dosage, several interventions (eg, use of electroconvulsive therapy, augmentation with mood stabilizers, participation in support groups, and obtaining guidance from mental health professionals) can facilitate improvement in patients and their family members.

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Vision Neuroscientist Marie Burns Appointed Interim Director of the Center for Neuroscience

Interdisciplinary center is the heart of neuroscience research and training at UC Davis

• by Kimberly Cummings
• July 09, 2024

Marie E. Burns , a professor in the Departments of Ophthalmology and Vision Science, and Cell Biology and Human Anatomy in the School of Medicine, and a core faculty member at the Center for Neuroscience (CNS), has been appointed the CNS interim director, effective July 1, 2024. 

Burns succeeds A. Kimberley McAllister , who has served as the center’s director since 2016 and who is departing UC Davis to begin a new position as Vice Provost for Research, Scholarly Inquiry and Creative Activity at Wake Forest University in the fall. 

An accomplished vision scientist, leader and mentor 

A highly respected and active member of the UC Davis neuroscience community, and a CNS core faculty member since 2001, Burns brings a wealth of leadership experience and a distinguished career in vision neuroscience research to her new role. She served as the inaugural director of the UC Davis Center for Vision Science from 2007–2012 and has been the director of the NIH Vision Science T32 Training Program since 2017. 

“Marie’s dedication to mentoring trainees and fostering an inclusive, collaborative research environment has been a hallmark of her career at UC Davis,” said Mark Winey, dean of the College of Biological Sciences. “Her leadership acumen and longstanding commitment to advancing neuroscience research make Marie an excellent fit for this interim role.” 

A third generation “eye doc,” Burns received her Ph.D. in neurobiology from Duke University and completed her postdoctoral training at Stanford University. “I am motivated by personal connections, my family members and friends affected by glaucoma and age-related macular degeneration,” said Burns. “I believe the work I do will directly impact the quality of care and treatment options within my parents' lifetimes."

Her research at CNS focuses on photoreceptors in the retina, the rods and cones in our eyes that detect light, in health and disease. The  Burns Lab uses innovative approaches to study photoreceptor signaling and interactions between photoreceptors and the immune cells of the retina in vivo.

“Bridging a uniquely broad range of research topics and approaches, the Center for Neuroscience has been a national leader in multi-disciplinary neuroscience research for decades, and I’m honored to step into the role of interim director during this transition," said Burns. "Together with the incredible faculty, trainees and staff at CNS, we will continue to advance the center’s mission, building on the strong foundation established over the past 30 years.” 

A decade of dramatic growth, innovation and discovery 

McAllister, who has dual appointments in the Department of Neurology in the School of Medicine and the Department of Neurobiology, Physiology and Behavior in the College of Biological Sciences, is a cellular and molecular neuroscientist who specializes in synapse biology and neuroimmunology. Over nearly 25 years at UC Davis, McAllister has trained 10 pre-doctoral and 13 post-doctoral fellows and more than 60 undergraduates and 13 post-bacs. She has been a CNS core faculty member since 2000.

From 2014–2016, McAllister served as the center’s associate director and in 2016 became the first woman named director of the center. As director, McAllister oversaw significant growth in the center’s research funding, training programs, and philanthropic support, and played a pivotal role in fostering collaborations and interdisciplinary initiatives within the broad neuroscience community across campus.

“Kim’s tenure as CNS director has been marked by numerous significant achievements and contributions to our community, and to the broader community of neuroscientists at UC Davis,” said Winey. “Her legacy, which is one of achievement and innovation, of collaborative, interdisciplinary partnerships across our campus, will be enduring.” 

During her tenure as director, McAllister expanded three research areas critical to the future of neuroscience discoveries: computational neuroscience, systems neuroscience and the field of neuroengineering. She also recruited seven CNS core faculty members, and greatly expanded NeuroFest , the center’s annual outreach event held each March during Brain Awareness Week. This event, which welcomes hundreds of visitors each year, has strengthened the center’s mission of engaging the public in neuroscience research. McAllister was also instrumental in creating the  CNS Director’s Circle , a special recognition program for donors who support ground-breaking research, outreach events and training fellowships at the center.

McAllister is also the founding director of the UC Davis Learning, Memory, and Plasticity (LaMP) T32 Training Program, Co-Director of the UC Davis Conte Center and Co-Champion of the Emerging Health Threats Grand Challenge.

“Serving as the director of the Center for Neuroscience for the past eight years has been one of the greatest honors of my life,” said McAllister. “I am immensely grateful for my UC Davis colleagues and proud of all we have accomplished together.”

About the Center for Neuroscience

Established in 1992, CNS is the interdisciplinary hub for neuroscience research and training at UC Davis. CNS faculty are leaders in cell/molecular, computational, cognitive, development and systems neuroscience and conduct cutting-edge research across a wide range of neuroscience approaches and subfields. We are committed to training the next generation of neuroscientists and engaging the public in neuroscience research.  Our commitment to diversity, equity, and inclusion permeates and elevates every aspect of our community.

Media Resources

• Kimberly Cummings, marketing and communications specialist, Center for Neuroscience, [email protected]

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