Joseph M. Pierre, MD

How do we, as clinicians, assess the benefits and harms of any medication, including but not limited to psychiatric medications? More specifically, how do we decide whether long-term antipsychotic treatment does more good than harm-or vice versa, as some critics of psychiatry have claimed? Certainly, a careful examination of the literature on relapse and remission rates in schizophrenia spectrum disorders is an important part of the answer.

However, we reject the notion that this is the only criterion for judging the risks and benefits of long-term antipsychotic use. Equally, we do not believe that armchair analyses of the literature by non-clinicians will answer the risk to benefit question in a humane and judicious manner. On the contrary, we believe that working with psychotic patients, and appreciating their often profound suffering, is an essential part of the equation. Critics of psychiatry who have never spent time with patients and families coping with the ravages of schizophrenia simply do not grasp the human tragedy of this illness. These critics also miss the deep-seated satisfaction that comes from seeing severely impaired patients achieve remission, and even recovery-in which antipsychotic medication usually plays an important role.

As clinicians with many years of experience in treating patients with 

, our views on antipsychotic medication are shaped not only by our understanding of the scientific literature, but also by our personal care of many hundreds of patients over several decades. Recent studies that pointed to the benefits of long-term antipsychotic use in schizophrenia, including reduction of relapse rates and the risk of suicide, were examined previously.

 Here we examine the concept of quality of life (QOL) and what we know about its relationship to antipsychotic use. We focus primarily on placebo-controlled studies, despite the paucity of such investigations in the published literature.

 noted in their 2003 review, the concept of QOL is relatively new in the psychiatric literature and “embraces a whole spectrum of uses and meanings.” In general, however, QOL refers to “. . . how patients feel and how satisfied they are with treatment, besides the traditional focus on disease outcomes.” In 1998, the World Health Organization described QOL in these terms: “It is a broad-ranging concept affected in a complex way by . . . physical health, psychological state, level of independence, social relationships and their relationship to salient features of their environment.”

 Berlim and Fleck list nearly a dozen instruments or scales designed to measure QOL, including the Quality of Life Scale (QLS), the Wisconsin Quality of Life Index (W-QLI), and the Medical Outcomes Study Short Form-36 Items (SF-36). The main items on the original (21-item) version of the QLS are shown in the 

 provide a comprehensive review of QOL in schizophrenia, based mainly on open-label and/or naturalistic studies. Only 2 studies compared QOL of patients who received an antipsychotic (either olanzapine or long-acting risperidone) with QOL of patients in the placebo group. Hamilton and colleagues

 evaluated patients (N = 76) over a 6-month period; Nasrallah and colleagues

 evaluated patients (N = 369) over 3 months. In both studies, patients who received the antipsychotic showed significantly greater improvement in QOL than those treated with placebo. Indeed, Nasrallah and colleagues found that long-acting risperidone (25 mg q 2 weeks) improved QOL to levels “not significantly different from normal,” based on the SF-36.

 acknowledge the “wide range of adverse [antipsychotic drug] effects that may negatively affect the quality of life” in patients with schizophrenia, and they observe that atypical antipsychotics may not improve QOL more than typical agents. Nevertheless, the authors conclude that “. . . the longer the length of the illness, the worse the quality of life . . . the combination of psychopharmacological and psychotherapeutic treatment improve quality of life.” They also observed that “. . . patients integrated in community support programs demonstrate a better quality of life than those who are institutionalized.” (Unfortunately, adequate outpatient and community supports are sadly lacking in many if not most parts of the US.)

One notable study not included in the review by Bobes and colleagues is that of Beasley and colleagues.

 This 52-week, double-blind, relapse prevention trial tested whether stable patients with schizophrenia who were taken off active drug treatment would experience greater improvements in long-term quality of life than those who were continued on antipsychotic treatment. The study found that, on average, Heinrichs-Carpenter Quality-of-Life Scale total scores improved by 4.3 ± 10.6 points during treatment with olanzapine (10 to 20 mg/d; n = 212), but decreased by 7.1 ± 14.6 points during treatment with placebo (n = 92; P < .001). The researchers also found that “. . . stable patients with schizophrenia who were taken off active drug treatment experienced no greater improvements in long-term quality of life than those who were continued on antipsychotic treatment, even in the absence of psychotic symptoms.”

 studied subjective well-being in patients with schizophrenia, using the Subjective Well-being Under Neuroleptic Treatment scale (SWN). (Subjective well-being overlaps substantially with QOL.) They reviewed open and controlled trials between 1994 and 2010, covering 44 studies. Most studies were short-term (< 1 year), and none used a placebo control; rather, most compared one antipsychotic with another, with regard to improvement on the SWN. However, 6 studies had a duration of 1 year or longer (up to 3 years). The key conclusion of this review was that “subjective well-being of patients with schizophrenia improved during treatment in almost all studies.”

Only a handful of placebo-controlled studies of QOL have been published since the 2007 article by Bobes and colleagues. Leucht and colleagues

 reviewed randomized trials that compared maintenance treatment with antipsychotic drugs compared with placebo, for persons with schizophrenia or schizophrenia-like psychoses. In addition to finding superiority of antipsychotic drugs compared with placebo in preventing relapse at 7 to 12 months, the researchers found some evidence that QOL was better in drug-treated participants (based on 3 randomized, controlled trials: n = 527; standardized mean difference, -0.62; confidence interval, -1.15 to -0.09).

 undertook an 8-week randomized, double-blind, placebo-controlled trial of olanzapine (long-acting injection) versus placebo in 404 acutely ill inpatients with schizophrenia. Participants were randomized to olanzapine long-acting injectable (LAI) 210 mg/2 weeks (n = 106); olanzapine-LAI 300 mg/2 weeks (n = 100); olanzapine-LAI 405 mg/4 weeks (n = 100); or placebo (n = 98). All active treatment groups were superior to placebo on the QLS total score (P < .01).

Finally, in an 8-week, randomized, placebo-controlled study of patients with acute schizophrenia, Isitt and colleagues

 compared a new sustained-release formulation of risperidone (RBP-7000) with placebo. Patients (N = 337) were assessed on health status, subjective well-being, treatment satisfaction, and preference of medicine. Health-related QOL (HRQoL) was measured using several scales. Findings indicated a significantly greater improvement in HRQoL and overall well-being in patients randomized to RBP-7000. Patients who received RBP-7000 also reported greater medication satisfaction on the Preference of Medicine Questionnaire (POM).

There are certainly large gaps in our knowledge of how antipsychotic medication affects “quality of life,” compared with placebo or no medication treatment. In particular, most studies are not randomized or placebo-controlled, and of those that are, most are short-term (< 1 year). Our conclusions, therefore, must be considered provisional. Nonetheless, our review finds no support for the notion that antipsychotic medication worsens QOL for patients with schizophrenia. Considerable controlled evidence shows that antipsychotic treatment improves QOL by various measures-at least within the first year of treatment, and perhaps for as long as 3 years.

 reviewed studies of patients with psychotic disorders that compared outcomes in those who received, or did not receive, antipsychotic medication during a follow-up period of at least 2 years. The researchers did not specifically study QOL; rather, they examined recidivism, negative symptoms, positive symptoms, and social functioning. Although the authors found the evidence base methodologically inadequate to determine the benefit-to-harm ratio of long-term antipsychotic use, they did not find evidence pointing to long-term harm from antipsychotics. Specifically, they concluded, “Our study did not support the hypothesis that long-term treatment with antipsychotic medication causes harm.”

Similarly, with regard to QOL, we find no placebo-controlled evidence that use of antipsychotics for up to a year causes any decline in QOL; indeed, the studies we reviewed show that antipsychotic treatment typically enhances QOL for patients with schizophrenia. That said, it is clear that we need more long-term (> 1 year), placebo-controlled studies of QOL and its relationship to antipsychotic treatment.

The decision to continue antipsychotic medication for the long term requires more than a survey of the research literature. It is a decision based, among other considerations, on the particular patient’s history; risk factors; response to initial treatment; adverse effect burden; and perhaps most important, the degree of suffering and incapacity the patient has endured as a consequence of having schizophrenia. Thus, careful assessment of the patient’s QOL should also be a part of the decision-making process, which should involve active and respectful collaboration with the patient (and, sometimes, the patient’s family). An ongoing process of informed consent and periodic monitoring of the patient’s response to treatment is essential.

The decision regarding long-term treatment is not a binary either/or choice; rather, the goal is to find the best medication and dose, with the fewest adverse effects. For some carefully selected patients with schizophrenia-and in most cases of “brief psychotic disorder”

-a slow tapering and discontinuation of antipsychotic medication may be warranted, with close monitoring of the patient’s response.

In our view, when non-clinician critics argue that most patients with schizophrenia would be “better off” without long-term antipsychotic medication-or that antipsychotics have done more harm than good-they misrepresent the best available evidence. Moreover, patients who impulsively discontinue their medication on the basis of such misinformation are jeopardizing their health, safety, and QOL.

 Our review suggests that amidst the shrill rhetoric of anti-psychiatry, the voices of patients who have done well on antipsychotic medication often go unheard.

Note: We use the term “schizophrenia” in the syndromal sense; ie, we recognize that the DSM-5 construct of schizophrenia most likely represents a “final common pathway” with several different etiologies; that there is probably a spectrum of schizophrenia-like conditions; and that the genetics and pathophysiology of schizophrenia probably overlap with other types of psychotic illness. The treatment of these conditions must be individualized, including decisions concerning the use of long-acting antipsychotic medication.

This article was originally posted on 8/10/2016 and has since been updated.

Dr Pies is Professor of Psychiatry and Lecturer on Bioethics at SUNY Upstate Medical University; Clinical Professor of Psychiatry, Tufts University School of Medicine; and Editor-in-Chief Emeritus of 

. Dr Pierre is Associate Director of Residency Education, UCLA Semel Institute for Neuroscience and West Los Angeles VA Medical Center; Acting Chief, Inpatient Psychiatry, West Los Angeles VA Medical Center; and Health Sciences Clinical Professor, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA. The authors report no conflicts of interest concerning the subject matter of this article.

The authors wish to thank Dr. Dieter Naber and Dr. A. George Awad for their helpful correspondence.

 Pies R. How antipsychotic medication may save lives. 

http://www.psychiatrictimes.com/blogs/couch-crisis/how-antipsychotic-medication-may-save-lives

 Pies R. Long-term antipsychotic treatment: effective and often necessary, with caveats. 

http://www.psychiatrictimes.com/blogs/long-term-antipsychotic-treatment-effective-and-often-necessary-caveats

 Berlim MT, Fleck MPA. Quality of life: presentation of the concept. 

 The World Health Organization. Quality of life assessment: development and general psychometric properties. 

 Heinrichs DW, Hanlon TE, Carpenter WT Jr. The Quality of Life Scale: an instrument for rating the schizophrenic deficit syndrome. 

 Bobes J, Garcia-Portilla MP, Bascaran MT, et al. Quality of life in schizophrenic patients. 

 Hamilton SH, Revicki DA, Genduso LA, Beasley CM. Olanzapine versus placebo and haloperidol: quality of life and efficacy results of the North American double-blind trial. 

 Nasrallah HA, Duchesne I, Mehnert A, et al. Health-related quality of life in patients with schizophrenia during treatment with long-acting, injectable risperidone. 

 Beasley CM Jr, Sutton VK, Taylor CC, et al. Is quality of life among minimally symptomatic patients with schizophrenia better following withdrawal or continuation of antipsychotic treatment? 

 Vothknecht S, Schoevers RA, de Haan L. Subjective well-being in schizophrenia as measured with the Subjective Well-Being Under Neuroleptic Treatment scale: a review. 

 Leucht S, Tardy M, Komossa K, et al. Maintenance treatment with antipsychotic drugs for schizophrenia. 

 Witte MM, Case MG, Schuh KJ, et al. Effects of olanzapine long-acting injection on levels of functioning among acutely ill patients with schizophrenia. 

 Isitt JJ, Nadipelli VR, Kouassi A, et al. Health-related quality of life in acute schizophrenia patients treated with RBP-7000 once monthly risperidone: an 8-week, randomized, double-blind, placebo-controlled, multicenter phase 3 study. 

 Sohler N, Adams BG, Barnes DM, et al. Weighing the evidence for harm from long-term treatment with antipsychotic medications: a systematic review. 

. December 14, 2015; Epub ahead of print.

 Memon MA, Bienenfeld D. Brief psychotic disorder. Medscape. November 17, 2015. (Updated). 

http://emedicine.medscape.com/article/294416-overview

 Frances A. Setting the record straight on antipsychotics. 

 http://www.psychiatrictimes.com/couch-crisis/setting-record-straight-antipsychotics

Awad AG, Voruganti LN. The impact of newer atypical antipsychotics on patient-reported outcomes in schizophrenia. 

Cortesi PA, Mencacci C, Luigi F, et al. Compliance, persistence, costs and quality of life in young patients treated with antipsychotic drugs: results from the COMETA study. 

Pies R. Trivializing the suffering of psychosis. 

http://www.psychiatrictimes.com/schizophrenia/trivializing-suffering-psychosis

Staring AB, Mulder CL, Duivenvoorden HJ, et al. Fewer symptoms vs more side-effects in schizophrenia? Opposing pathways between antipsychotic medication compliance and quality of life. 

Strakowski SM, Johnson JL, Delbello MP, et al. HGDH Research Group: quality of life during treatment with haloperidol or olanzapine in the year following a first psychotic episode. 

Articles

The authors examine the literature on "quality of life" and how antipsychotics improve that for patients with schizophrenia.

Quality of Life and the Case for Antipsychotics

Essentials of Psychiatric Diagnosis: Responding to the Challenge of DSM-5

by Allen Frances, MD;
New York: The Guilford Press; 2013

[A note from the publisher: The revised edition features ICD-10-CM codes where feasible throughout the chapters, plus a Crosswalk to ICD-10-CM codes in the Appendix.]

Although I am fond of saying that DSM-5 is still a “good enough guide for clinical work,” 

 is a sort of guide to that guide. Perhaps the book is in the same vein as the APA 

-which Dr Frances co-authored in 1995 in his role as DSM-IV chairperson. This time, however, Dr Frances writes as a DSM-5 critic rather than an insider. This easy-to-read manual represents his concise views on how to achieve “more accurate” 

, as well as when to avoid DSM-5 altogether.

The book is made up of 18 chapters covering major categories of psychiatric disorders, with a screening question (eg, “Do you ever get so depressed that you can’t function?”). This is followed by a clinical description of a patient, as an adjunct to DSM-5 diagnostic criteria (which are not included). Brief sections on differential diagnoses and diagnostic tips follow.

Although written in a casual style, much of the information represents the kind of valuable clinical wisdom that one accumulates after years of diagnostic experience. These clinical pearls focus on the fuzzy boundaries and gray areas between threshold diagnoses and non-diagnostic problems of living, as well as Dr Frances’ concerns about diagnostic inflation in psychiatry. For example, he cautions that 

ADHD is sometimes overdiagnosed in children

 who are born at the end of the calendar year because they are less mature than their grade-matched peers.

Dr Frances also offers black box cautions for diagnoses he believes represent the greatest risk of being overdiagnosed. For example, he favors using the bereavement exclusion for major depression that was removed from DSM-5 and warns against conflating normal childhood behavior with bipolar disorder and ADHD. He also recommends using ICD criteria for substance abuse and dependence rather than the unified definition of addiction in 

. He advises abandoning the use of disorders that he believes should not have been included in DSM-5 (eg, mild neurocognitive disorder, dissociative identity disorder). These black box warnings represent areas of controversy that are clearly stated as Dr Frances’ personal recommendations; it is up to the clinician to decide whether it is practical or useful to boycott entire sections of DSM-5.

Using a decidedly Kraepelinian perspective, Dr Frances emphasizes the clear difference between psychiatric disorders and the suffering of normal life. He realizes that diagnostic boundaries are fuzzy but falls short of acknowledging a mental illness–mental health continuum and recognizes the potential value of diagnosing minor disorders and subthreshold states.

Much of this volume offers sound clinical wisdom that will be particularly insightful to those with limited clinical experience, as well as those of us suffering from “clinician’s bias,” whereby all mental health consumers are assumed to be mentally ill (or are assigned a diagnostic code in any case to justify insurance reimbursement). Reading this book may very well help temper overzealous diagnosis and intervention.

This article was originally posted online on 8/13/2014 and has since been updated.

Dr Pierre is Associate Director of Residency Education at UCLA Semel Institute for Neuroscience; Health Sciences Clinical Professor in the department of psychiatry and biobehavioral sciences at David Geffen School of Medicine at UCLA; and Co-Chief of the Schizophrenia Treatment Unit at West Los Angeles VA Medical Center.

This easy-to-read manual represents the author's concise views on how to achieve “more accurate” diagnoses with DSM-5, as well as when to avoid DSM-5 altogether.

When I was an undergraduate studying molecular biology in the early 1990s when the Human Genome Project had just begun, my required coursework included several lectures on the ethical implications of sequencing, understanding, and ultimately being able to manipulate the “code of life.” As members of the generation that might one day be able to purposefully alter individual gene expression, our class was urged to consider the vital questions arising from such potential-How should the new technology be applied? For whom and in what situations? Should it be done at all?

As DSM-5 is being drafted, on the heels of the promise of a “paradigm shift,”

 I find myself thinking again of such questions, and at the same time wondering why psychiatry as a field, from the top down, does not seem to be widely discussing them. Certainly a debate has been ignited, fueled by the likes of old-guard DSM architects Drs. Robert Spitzer and Allen Frances on the one hand, and current DSM-5 framers forging relentlessly onward to 2013 on the other. But that debate has many facets involving both content and process, and in my mind the most fundamental issues-for example, what constitutes a mental illness and what are the appropriate targets of psychiatric intervention-often seem to be lost in the shuffle.

Towards a Spectral Model of Mental Illness


I have long been fascinated by the “grey areas” of mental illness-those hard to define intermediate zones between normal and pathologic modes of behavior-but have usually found myself siding with those wary of diagnostic expansion. Perhaps that’s an expected stance for a psychiatrist primarily working on an inpatient unit focusing on the treatment of psychosis, where drawing a line in the sand to demarcate pathology is often, though not always, fairly straightforward. On the other hand, I’ve also worked at the other end of the psychotic spectrum, in a “prodromal schizophrenia” research clinic, where debate about the boundaries of mental illness was a daily discussion. As DSM-5 moves towards a more dimensional view of mental illness with the proposal of a “psychosis risk syndrome” and the broadening of other diagnostic categories, the time is ripe for us all to pause and carefully consider the implications of this direction.

The idea of conceptualizing mental illness on a spectrum that spans from normal behavior to clear disorder is not new. Incorporation of a dimensional model was considered for DSM-IV, but eventually abandoned due to “serious limitations,”

 including the belief that categorical boundaries are vital to clinical decision making. In order to define those boundaries more reliably, DSM-IV was the first edition of the manual to fully integrate a requirement of “clinically significant distress or impairment of functioning” into the criteria for each disorder (though the “not otherwise specified (NOS)” disorders lack both symptomatic criteria and any explicit requirement of distress/impairment). In contrast, recognizing that few patients neatly fit DSM-IV disorder criteria and that NOS diagnoses abound, a central agenda for DSM-5 has been to move towards a dimensional view of mental disorder.

There are reasonable arguments on either side of the debate over such dimensionalization. On the one hand, those wary of adopting a spectral view of mental disorder are concerned that psychiatry is already guilty of over-diagnosis, with the number of cataloged mental disorders more than tripling from DSM-I (106 disorders) to DSM-IV (357 disorders) and the most recent epidemiologic studies indicating that about half of Americans will meet criteria for a DSM-IV disorder at some point in their lives.

 With dimensionalization, this diagnostic boundary will almost surely be expanded further, suggesting that if it’s not already the case, it will soon be “normal” to have a mental illness. Such alarming and seemingly oxymoronic conclusions threaten the already shaky reputation of psychiatry in the public eye, where many are already worried that “psychiatrists think everyone is crazy.” Professional skepticism about diagnostic expansion is just as abundant, particularly with specific DSM disorders such as major depression,

 attention deficit hyperactivity disorder (ADHD),

 At their core, each of these arguments contends that psychiatry is overstepping its bounds by applying a label of pathology to some variant of normal human existence and behavior.

On the other side of this debate, defenders of diagnostic expansion argue that available research findings do support identification of and intervention at the “soft” end of spectral conditions such as bipolar disorder, depression, and psychosis. At a phenomenologic level, the dimensionalization position is intuitively defensible given that many of the core symptoms that make up DSM criteria-anxiety, dysphoria, and even psychosis-are indeed part of normal everyday human existence. Admittedly, for me this is one of the things that makes psychiatry so interesting-the very real sense that mental illness is, to paraphrase Susanna Kaysen,


Ever since DSM-III, the hope has been that neurobiological research of categorical diagnoses would result in the discovery of underlying pathophysiologies that would in turn elevate DSM disorders to the status of “disease entities.” Thirty years later, that vision remains unrealized. For DSM-5 and beyond, the new hope is that a spectral view of mental illness that addresses the continuum between mental disorder and mental health will better facilitate etiologic research resulting in the discovery of underlying mechanisms of symptoms as opposed to disorders 

 (e.g. it is more likely that mechanisms for “fear” or “paranoia” will be discovered than for “PTSD” or “schizophrenia”). Perhaps when future revisions are truly informed by research into spectral models of mental illness, a DSM reflecting a true “paradigm shift” will bear little resemblance to DSM-IV or DSM-5 and will instead take the form of something more akin to the Research Domain Criteria (RDoC) currently in development at the National Institutes of Mental Health.

If the promise of that vision is realized, the end-game in psychiatric research will include not only the elucidation of “pathologic” processes, but “normal” neuropsychologic processes as well-just as the early study of simple genetic mutations paved the way for the full sequencing of the DNA code in the Human Genome Project. Therefore, while the hope has been that the discovery of underlying pathophysiologies would result in the validation of psychiatric disorders, it becomes apparent that discovering an underlying biological mechanism to account for a mental process or behavior does not alone make it pathological. Thresholds of “pathology” or “disorder” will always require some value-based judgment about “clinical significance”

 On the other hand, what elucidated genetic or biochemical mechanisms do reveal is the potential to intervene using biologically-based strategies.

While I have spent considerable time pondering what is and is not a mental disorder, and wondering whether it “should” be the role of psychiatrists to intervene at the soft end of disorder spectrum,

 it appears that such debate is becoming increasingly academic rather than clinically pertinent. Clinical intervention is not and will not be dictated by DSM definitions of mental disorder, but by the discovery and availability of interventions. Intervention already occurs across a spectrum of suffering, from traditional medical diseases (e.g. cancer) by medical doctors to “problems of everyday life” by clergy and all points in between. What will change as the doors of dimensionalization open into the psychiatry of tomorrow is the potential, through pharmacologic and other “somatic” interventions, to change the course of both pathologic as well as normal mental processes and behaviors. Such potential to make people “better than well” through “cosmetic psychopharmacology” was widely discussed at the beginning of the selective serotonin reuptake inhibitor (SRRI) era with the publication of 

 but has since been strangely absent in mainstream American psychiatry.


Perhaps clinicians and patients feel comfortable relegating questions about whether this is where psychiatry “should” be headed to the domain of ethics. Indeed, some have now proposed the creation of a specific branch of “neuroethics” where debates about “neuroenhancement” are already ongoing.

But these issues are not merely ethical or philosophical, as if a part of some imagined, futuristic 

. As scientific discovery and DSM embrace a spectral view of brain disorder and inch more closely to unraveling the biological basis of not only “disease states,” but normal mental processes and behaviors as well, these questions will become more timely and pertinent before we know it. As such, it is already time for DSM architects, clinicians, researchers, patients, and families to seriously ponder them.

Although such discussions have begun to emerge concerning the development of the “cognitive enhancers,”

 the questions that arise-Who should get them? Would taking them confer an “unfair advantage” upon those with access to them? Would you still be the same person if you took them? How would their widespread use transform our notions of “normal” vs. “ideal” functioning? Could some individuals be mandated to take them? Should they be regulated? Should psychiatric physicians be involved in the practice of enhancement? Should insurance companies reimburse for such therapies?-apply to 

 future interventions for the softer end of the mental illness spectrum.

Elsewhere, I cautioned that:
“The intrusion of diagnostic labels onto traits and behaviors previously considered normal threatens the legitimacy of psychiatry as a medical field. At its worst, it paves a path from well-intentioned cosmetic psychopharmacology to the perils of eugenics.”

Accordingly, and echoing concerns about “unintended consequences” voiced by Dr. Frances,

 it is now important to cautiously consider how the inclusion of spectral views of mental disorder in DSM-5 could contribute to inappropriate medicalization of “problems of daily living” and the sanctioning of pharmacologic interventions for conditions where evidence-based practice does not yet exist (e.g. indiscriminate use of antipsychotics for the “psychosis risk syndrome”). While no skeptic of diagnostic expansion is arguing that we shouldn’t intervene for all forms of suffering, both mild and severe, a careful analysis about how best to intervene based upon controlled research is absolutely necessary. Likewise, at some point, psychiatrists will have to decide whether our field should expand to include neuroenhancement towards an ideal of “perfect” functioning or whether our goal is to help people cope with the normal, inherent suffering of everyday life and the natural limitations of the human body. Anyone is entitled to the right to the “pursuit of happiness,” but it is worth considering whether that “pursuit” is best conceptualized as a Sisyphean process distinct from attainment or satisfaction.

At the same time, I believe that for many domains of psychopathology, a spectral view does reflect biological reality and that etiologic discoveries do require a shift to dimensional models of mental illness. However, DSM-V doesn’t need to exist for a dimensional approach to research to take place-such inquiry has already been ongoing for years. In fact, I would argue that DSM revisions should follow this kind of research rather than the other way around. Yet it seems that the move towards dimensionalization in DSM-V has already begun and that an immediate impact on clinical practice is inevitable. It is within arenas in which categorical judgments about mental pathology are both essential and have significant and potentially harmful consequences-the aspects of clinical intervention described above as well as with the various “third parties” that use DSM (e.g. governments deciding resource allocation, insurance companies reimbursing for care, the legal system making decisions about moral responsibility)-that thoughtful decisions must be made about how best to adapt to a spectral view of mental illness. It is therefore our collective destiny that ethical discussions about what could occur will soon become practical discussions about what does occur.

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When I was an undergraduate studying molecular biology in the early 1990s when the Human Genome Project had just begun, my required coursework included several lectures on the ethical implications of sequencing, understanding, and ultimately being able to manipulate the “code of life.”

A Psychiatry of Tomorrow: DSM-5 and Beyond

I greatly enjoyed Dr Ron Pies’ editorial 

“What Should Count as a Mental Disorder in 

 to critically examine the boundaries of mental illness and to more carefully distinguish between diseases, disorders, and syndromes. As I have noted elsewhere, current plans to integrate a “spectrum” approach into 

 require a careful consideration of these issues that must be defensible to critics of diagnostic expansion within psychiatry.

’s requirement of “distress and impairment” for most of its disorders, Dr Pies begins with “suffering and incapacity” as core fibers to craft a model of mental disease. He then proposes that progressive discoveries about pathophysiology elevate a syndrome in step-wise fashion toward a disease entity. While this model seems logical enough, I would like to review several challenges that arise from any model that is based on a foundation of “dis-ease.”

The first is the Szaszian issue of society’s role in defining (or creating) suffering and impairment in the context of behavioral disorders. Dr Pies specifically emphasizes the importance of phenomenology-the subjective experience of distress-and also requires that suffering be inherent to the disorder rather than imposed by society (eg, as punishment for deviance). But thinking Socratically, what about conditions in which subjective dis-ease is absent? And what of conditions in which incapacity is defined only by impaired social functioning? Isn’t it sometimes true that a patient with schizophrenia with no insight and no complaints about his or her homelessness, unemployment, and “symptoms” is hospitalized involuntarily because of society’s paternalistic, if not punitive, view of impairment? If that example seems to have obvious holes, what of the thorny history of 

 and homosexuality-if presently excluded based on lack of intrinsic suffering,

 should that same status now be extended to paraphilias (for example,  pedophilia)?

Dr Pies notes that value judgments are unavoidable in diagnosis and notions of disorder and argues that this does not detract from “facts.” In his model, the “facts” seem to be manifest symptoms or known pathophysiologies. Does this mean that any condition with a known physiology that is associated with value-laden suffering or incapacity qualifies as a disease entity? Should human variations that result in less than ideal social functioning and that are almost assuredly rooted in “biomolecular etiology” (eg, ugliness, shortness, baldness, shyness, diminutive sex organs) be categorized as disorders or diseases?

 Part of this dilemma can be sidestepped by arguing that “pathological” suffering should be defined by some threshold of severity, such that therapeutic and cosmetic interventions can be disentangled. But anyone who has ever used a visual analog scale to measure a patient’s self-reported pain can appreciate the difficulties arising from such subjectivity.

Finally, it would appear that disease models that start with “dis-ease” are based on the assumption that “normal” existence does not or should not involve “prolonged suffering or incapacity.” In contrast, Freud wrote of the “common unhappiness” inherent to the human condition-a view now mirrored by proponents of acceptance and commitment therapy,

 Horwitz and Wakefield’s critique of depression,

 or those lamenting “disease mongering.”

 Here the underlying issue is causation: is prolonged suffering and incapacity caused by intrinsic pathophysiology, or is subjective dis-ease a “normal” response to extrinsic circumstances (eg, poverty, war, oppression, a less than ideal childhood development)? Such etiological distinctions were deliberately abandoned in 

 but seem to be vitally important to the task of defining disease.

These issues are hardly novel and on the contrary have confronted each wave of 

 architects. One can only hope the changes occurring in 

 will represent a step forward in accounting for these challenges.

Joseph M. Pierre, MD 
Associate Director of Residency Education 
UCLA Semel Institute for Neuroscience 
West Los Angeles VA Medical Center 
Co-Chief, Schizophrenia Treatment Unit 
West Los Angeles VA Medical Center 
Associate Clinical Professor 
Department of Psychiatry & Biobehavioral Sciences 
David Geffen School of Medicine at UCLA

1. Pies R. What should count as a mental disorder in 

http:// www.psychiatrictimes.com/display/article/ 10168/1402032.

 Accessed August 5, 2009.
2. Pierre J. Deconstructing schizophrenia for 

: challenges for clinical and research agendas. 

. 2008;2:166-174.
3. Spitzer RL. The diagnostic status of homosexuality in 

. 1981;138:210-215.
4. Silverstein C. The implications of removing homosexuality from the 

. 2009;38:161-163.
5. Moynihan R, Heath I, Henry D. Selling sickness: the pharmaceutical industry and disease mongering. 

. 2002;324:886-891.
6. Hayes SC, Strosahl KD, Wilson KG. 

Acceptance and Commitment Therapy: An Experiential Approach to Behavior Change

. New York: Guilford Press; 1999.
7. Horwitz AV, Wakefield JC. 

The Loss of Sadness: How Psychiatry Transformed Normal Sorrow Into Depressive Disorder

. Oxford, UK: Oxford University Press; 2007.
8. Smith R. In search of “non-disease.” 

I appreciate Dr Pierre’s thoughtful comments on my editorial, as well as his very useful article.

 Among many other issues, Dr Pierre raises the question of what he calls “the Szaszian issue of society’s role in defining (or creating) suffering and impairment.” It is nearly impossible, in this space, to provide a critique of Dr Szasz’s views-which I and others have criticized at length.

 Instead, I will try to answer the specific questions raised by Dr Pierre.

First, though, some foundational assumptions: I believe we need to distinguish carefully between the 

. The latter is the subject of Dr Pierre’s excellent article, in which he examines various methods by which psychiatric diagnoses may be “categorized” (eg, based on underlying pathophysiology, clinical manifestations, or both).

My contention is that these issues ought to follow the 

 of disease, which, in my view, is an everyday determination made on the basis of intrinsic suffering and incapacity of a certain kind. The classification or categorization of such conditions comes later-and constitutes the “upper stages” of the pyramidal model depicted in my editorial. As to the role of causation and etiology: I believe these are unquestionably important in determining the 

 of disease that afflicts the patient, but not in determining that the patient 

Let me be clear: my model does not regard 

 instances of prolonged suffering and incapacity as instantiations of disease. A person may experience prolonged suffering and incapacity as a consequence of poverty, physical abuse, or terrorism and would not be considered “diseased” in the sense I wish to define, or in our ordinary usage of the term. 

Thus, disease entails prolonged and substantial intrinsic suffering, as well as incapacity, in the absence of an obvious exogenous factor that maintains the condition

My second assumption is that the construct of disease needs to be “uncoupled” from the issues of its 

. That is, the primordial construct of disease is independent of whether we happen to have useful therapies for the patient or whether we decide to hospitalize the patient, either voluntarily or involuntarily. Thus, the thorny legal and ethical issues surrounding involuntary hospitalization are logically distinct from the concept of what counts as psychiatric disease. That said, I believe that involuntary psychiatric hospitalization is justified only when the individual is clearly a danger to self or others; or is so markedly unable to care for himself that he is in danger of death or severe bodily injury.

Finally, my model does not assume that only diseased persons warrant medical care and attention. After all, reconstructive surgeons routinely perform “reduction mammoplasty” without claiming that having large, pendulous breasts constitutes a “disease.” Similarly, there are many emotionally disturbed or dissatisfied individuals who are, in some sense, “suffering” but not incapacitated, or incapacitated but not suffering, and who may nevertheless benefit from psychiatric interventions-yet they would not be called “diseased” using my schema.

On the other hand, the legal system sometimes places psychiatrists in the uncomfortable position of having to provide involuntary “treatment” to individuals-such as serial sexual predators-who are 

, but who are deemed a threat to society. These persons may in some sense be “disordered,” but I would not regard them as “diseased.” Under certain legal doctrines, society may have a right to keep them confined, but it is far from clear that they will benefit from psychiatric hospitalization.

With this background in mind, my responses to Dr Pierre’s questions are as follows:

1. Conditions in which subjective “dis-ease” is usually absent and that typically lack “intrinsic suffering”-for example, ego-syntonic pedophilia-should not be considered instantiations of disease, although they may require societal intervention or control.

2. Regarding patients with schizophrenia but who have “no complaints about . . . homelessness, unemployment, and [their] ‘symptoms’ . . . ”: such individuals are extremely rare, in my clinical experience. While it is true, as Dr Pierre notes, that “delusions and hallucinations may or may not be subjectively distressing,”

 it would be exceedingly rare for someone with chronic schizophrenia to have experienced no intrinsic suffering as a result of this condition. Such suffering may not be a direct consequence of hallucinations or delusions but may stem from severe dysregulation of volition, motivation, mood, and “ego integration.”

 These phenomena are not merely examples of “social” impairment, nor are they merely the result of society’s disapproval or “labeling.” Rather, they are 

intrinsic experiential dimensions of the person’s psychosis

 himself points out, many individuals with schizophrenia experience neurocognitive difficulties that limit their ability to process and analyze information, resulting in both incapacity and subjective distress.

3. With respect to what Dr Pierre calls “human variations that result in less than ideal social functioning” and that have “a known physiology,” such as shortness or baldness: such normal variants would not constitute disease, using my model, because they are not typically associated with intrinsic suffering and substantial incapacity (although they may be the objects of derision or discrimination).

4. My model of disease does not rest on the assumption that “normal” existence does not, or “should not,” involve prolonged suffering or incapacity. However, I do assume that physicians have an ethical and humanitarian interest in reducing disease-based suffering and incapacity.

In closing, I would emphasize that there is no “correct,” objectively verifiable definition of psychiatric disease or mental illness that we have yet to “discover”-as if we were hunting for some buried treasure that has mysteriously eluded us. Nor is there ever likely to be a universally useful definition of “disease” that covers all legitimate cases and excludes all spurious ones. I believe Dr Pierre appreciates this when he writes that “medical diagnosis serves different functions” ranging from communication to treatment to definition of pathophysiology.

Indeed, in my view, what we call “disease” or “disorder” is radically dependent on specific human needs, goals, and purposes. A definition of disease that may serve the purposes of an infectious disease expert may not serve those of an internist or psychiatrist. To borrow from Ludwig Wittgenstein: we may ultimately be left with a “family” of conditions we call disease, which lack any necessary and sufficient defining features, but which cohere in so far as they entail severe and prolonged suffering and incapacity.

Ronald Pies, MD
Professor of Psychiatry 
SUNY Upstate Medical University 
Syracuse 
Clinical Professor of Psychiatry 
Tufts University School of Medicine 
Boston 
Editor in Chief, 

1. Pierre J. Deconstructing schizophrenia for 

 2008;2:166-174.  
  2. Pies R. On myths and countermyths: more on   Szaszian fallacies.

. 1979;36:139-144.  
  3. Pies R. Moving beyond the “myth” of mental illness. In: Schaler JA, ed. 

>I greatly enjoyed Dr Ron Pies’ editorial “What Should Count as a Mental Disorder in DSM-V?”1 in which he encouraged framers of DSM-V to critically examine the boundaries of mental illness and to more carefully distinguish between diseases, disorders, and syndromes. As I have noted elsewhere, current plans to integrate a “spectrum” approach into DSM-V require a careful consideration of these issues that must be defensible to critics of diagnostic expansion within psychiatry.2

Author | Joseph M. Pierre, MD

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