NeedsFixing

It is increasingly appreciated that comorbidity in psychiatric illness is an important consideration in clinical practice; it has also become a topic of research interest. Many recent articles highlight the complexity of psychiatric and systemic illness, both in terms of overlapping clinical presentation and in the degrees to which systemic illness and psychiatric illness affect each other. 

(A literature review that offers a sample of these articles can be viewed in the online version of this article here.)

When one speaks of psychiatric comorbidity, 2 constructs come to mind. The first is psychiatric illness that is comorbid with systemic medical illness. Whether the onset of the psychiatric illness is temporally associated with the systemic illness, whether the psychiatric illness comorbidity can be explained by the patient not coping well with the systemic illness, or whether both are referable to a common source is often elusive and ambiguous. What matters is that the patient has 2 (or more) medical problems (that affect different organ systems) that need to be addressed by evidence-based clinical interventions in an integrated approach.

The other “psychiatric comorbidity” refers to more than one psychiatric illness in the same patient. Examples include dementia with episodic delirium, depression with concurrent substance abuse, and personality disorder comorbid with PTSD. Indeed, for some particularly complex psychiatric patients, one may speak of “trimorbidity” (eg, mood disorder, personality disorder, and substance abuse), even in the absence of significant systemic illness. Of course, physicians are quite familiar with patients who are “multiply comorbid” on 2 dimensions (ie, 2 or more chronic systemic illnesses and 2 or more psychiatric illnesses) simultaneously.

The semantics of all of this can be daunting and less than precise. What is important, for psychiatrists and other specialty physicians, is to be vigilant for comorbidity within the category of psychiatric illness and to look for psychiatric and systemic comorbidity simultaneously. Care for these various conditions should be integrated and balanced, so that various medical interventions do not work at cross purposes. Comorbidity can serve as the illnesses’ “substrate” that encourages the patient’s various specialty physicians to thoughtfully collaborate and complement their respective interventions.

The authors of this Special Report-which will appear in this issue and also in February and which can now be read online at www.psychiatrictimes.com-have chosen a compelling series of topics. In her article, 

, addresses the psychiat-ric comorbidity of painful and life-limiting illnesses. She emphasizes that these systemic conditions both mimic primary psychiatric illnesses and are frequently comorbid with them. The inclusion of the Fukuda and Canadian criteria is a timely addition. Dr Stein specifies which symptoms of myalgic encephalomyelitis and fibromyalgia overlap with psychiatric illness and which do not, adding diagnostic and attributional specificity. She suggests that conventional psychiatric interventions such as psychotropic medication and psychotherapy may be indicated for the “non-psychiatric” systemic illnesses as well as for their comorbid psychiatric conditions. The specification of cognitive-behavioral therapy as the chosen psychotherapy model for pain conditions is especially important.

, describe the synergistic and often “reciprocal” relationship between depression and diabetes. Because these two illnesses are, independent of each other, major public health problems worldwide, thoughtful management of their commonly overlapping presentations is especially crucial for patient outcomes. The authors describe the pervasive effects diabetes and depression each have on the other. Their guidance on attributional interpretation of symptoms is particularly helpful.

, straddles the neuropsychiatric borderland in his article. It is often best to think of many CNS phenomena as neither exclusively psychiatric nor exclusively neurological, but as both. He provides concise and clinically utilitarian descriptions of the various movement disorders encountered in psychiatric practice and offers useful management approaches.

Todd Smitherman, PhD, Donald B. Penzien, PhD, and Jeanetta C. Rains, PhD

, review a common clinical relationship between migraine and psychiatric illness. Because psychiatric comorbidity is both common and complicating, physicians are reminded to consider migraine and its psychiatric comorbidity in an integrated fashion. Both psychopharmacological and nonpsychopharmacological treatment should be actively considered.

, describe the complex and often multiple psychiatric comorbidities that affect patients with borderline personality disorder, one of the more complex and common patient presentations in clinical practice. The authors remind us that simultaneous attention to these comorbidities is crucial in the clinical management and treatment outcomes for these patients.

These articles illustrate the variety and complexity of problems associated with comorbidity in psychiatric disorder. We hope that physicians who daily face the challenges of often multiple psychiatric illnesses in patients with significant comorbidity will find these articles useful.

Articles

 These articles illustrate the variety and complexity of problems associated with comorbidity in psychiatric disorder.

Introduction: The Integrated Approach to Addressing Comorbidities-Part 1

In this podcast, Ms Gareth Fenley and Dr Lisa Dixon, our Special Report chairs for patient education, provide a brief overview of articles that provide an opportunity for patients to help themselves.

Gareth Fenley is a Certified Peer Specialist in the Department of Psychiatry and Health Behavior at the Georgia Health Sciences University; Lisa Dixon is Professor at the University of Maryland School of Medicine, Director of Health Services Research, and Action Director of the VA Capitol Health Care Network MIRECC.

Patient Education as Treatment Foundation

Educating Patients About Bipolar Disorders

Chronic Disease Self-Management Programs in Psychiatry

Podcasts

Special Report chairs discuss patient education and provide a brief overview of materials that provide an opportunity for patients to help themselves. 

Podcast: Current Trends in Patient Education

Generic education has long been a component of psychiatric treatment. At a very basic level, ethics and regulations require physicians to provide information about the risks and benefits of medication. Patient education and psychoeducation programs have been studied for decades as strategies to improve outcomes.

Fundamental underpinnings and assumptions of patient education have evolved markedly over the past decade. Patient-centered and recovery-oriented care have reshaped medical practice. Patient education is best seen as an agent of shared decision making that reflects mutual collaboration among patients, families, and clinicians. This perspective expands education from a treatment component to a treatment foundation.

A critical point in this approach is that collaboration shifts the emphasis away from doctors telling patients what to do; instead, together doctors and patients decide what to do. Although sometimes patients may prefer less decision-making responsibility, in the long run, patients are better at treatment adherence when they make their own choices.

Psychiatrists can use educational strategies to address specific goals and needs. We can provide information about specific treatment areas, and beyond that, we can teach patients and families the process of how to educate themselves. With appropriate educational strategies, psychiatrists can address and match diverse goals, competencies, preferences, and practical means of access. We can teach patients and families to become wise consumers of the information they will encounter outside the clinical setting. Together we can identify resources that will inform healthy choices. Collaboration will ultimately improve outcomes.

 With appropriate educational strategies, psychiatrists can address and match diverse goals, competencies, preferences, and practical means of access.

Introduction: Patient Education as Treatment Foundation

The Specific Efficacies of CBT and IPT Have Not Been Established

In the past few years, large meta-analyses of antidepressant drug treatments for major depression have failed to show distinct advantages over placebo. The authors of one such report provocatively concluded that the new antidepressant drugs are either placebos or act as placebos and therefore are not clinically meaningful. Some authors have argued that such findings advance the utility of the evidence-based nondrug treatments-cognitive-behavioral therapy (CBT) and interpersonal psychotherapy (IPT).

But what holds for the goose often holds for the gander. We have undertaken reviews of both CBT and IPT as treatments for major depression.

 When compared with plausible control psychotherapies, they also showed minimal differentiation. Just as some authors claim that the evidence shows that antidepressant drugs are no more than placebos, the same suggestions have been put forth about CBT and IPT. For instance, the psychologist Gary Greenberg

advanced the view that CBT is more an ideology and a “method of indoctrination into the pieties of American optimism.”

The key issue then is why do the so-called evidence-based or empirically supported treatments (ESTs) for depression (ie, antidepressant drugs, CBT, IPT) produce this perplexing result when all 3 are invariably positioned in treatment guidelines as the mainstay of treatment for managing depression?

We offer 2 principal reasons here. First, we outline the methodological limitations of psychotherapy efficacy research and the role that this has played in falsely positioning CBT and IPT as first-line or superior treatments for depres-sion. As part of this, we consider what is meant by the placebo effect. Second, we discuss the negative impact of universally applying treatments across nonspecific disorders, such as major depression.

The supportive evidence base for CBT and IPT as superior treatments for major depression is less substantive than generally considered because of 3 critical methodological flaws in efficacy research.

 First, differential effects generally disappear when analyses are limited to therapies that are intended to be therapeutic (bona fide therapies). For example, when meta-analyses specifically removed non–bona fide therapies, CBT did not differ from other psychotherapies for acute-phase treatments of major depression.6 A more recent meta-analysis quantified comparable effects when contrasting IPT (eg, coping-oriented couples therapy, supportive psychotherapy) with other psychotherapies, including CBT for depression-a finding that is consistent with our review of IPT studies.

Studies or meta-analyses that have shown the superiority of CBT and IPT have generally used benign, ineffective control strategies (eg, wait-list assignment) in randomized controlled trials (RCTs), leading to false positioning of CBT and IPT as superior treatments. Treatment-as-usual comparators also tend to favor the active psychotherapy, because therapist enthusiasm, patient expectancy, and other common factors are less likely to be activated in the treatment-as-usual condition.

For example, the meta-analysis undertaken by Cuijpers and colleagues

 reported a moderate to large effect of IPT in the acute treatment of depression compared with other treatment methods. Control groups in RCTs of the effectiveness of psychotherapy consisted of treatment as usual; wait-list; and inert nontherapies, which risked false boosting of IPT effect sizes. Requesting a therapist to be inert (in so-called clinical management) or to provide a psychotherapy with only nonspecific therapeutic ingredients is difficult for any therapist to implement.

We are not asserting that all treatments are equal, but rather that flawed procedures and paradigms may obscure quantification of true treatment efficacy. Nonetheless, the evidence to date does not support the reified status of CBT and IPT as universal treatments for treating clinical depression.

Evaluating psychotherapies (especially CBT and IPT) is made even more difficult by a second key methodological issue-the role of nonspecific therapeutic factors. Evidence of psychotherapy’s benefits that emerge from its 

ingredients (ie, techniques and therapeutic approaches integral to the therapy’s theoretical model) is lacking; meta-analyses have quantified that only an 8% variance in psychotherapeutic outcome was accounted for by such a specific therapeutic component.

 Furthermore, dismantling designs have shown that key components of CBT were not responsible for therapeutic benefit, and others have observed that most improvement occurs before the formal introduction of cognitive restructuring techniques.

Most of the improvement during psychotherapy is therefore likely to be a consequence of nonspecific effects common to all therapies-namely, an emotionally charged confiding therapeutic relationship, a healing setting, a clear rationale, and a treatment procedure believed by both patient and therapist to be restorative.

psychotherapeutic ingredient is low-with estimates of up to only 15%-this makes it extremely difficult to quantify its 

 when compared with any other plausible psychotherapy that provides those nonspecific ingredients.

This issue also helps explain why meta-analyses that support CBT and IPT show significant differences only when the control therapy lacks the key nonspecific therapeutic ingredients. Proper evaluation of the effectiveness of CBT and IPT therefore needs to recognize this major methodological limitation.

This general finding is worthy of some clarification. The use of the term “placebo-controlled trials” has a clear connotation-that the nonactive-treatment group receives a placebo or, by definition, an inert treatment. But should we equate the beneficial nonspecific effects of a therapeutic intervention-whether as a component of psychotherapy or of good clinical care when a therapist principally prescribes an antidepressant drug-as necessarily inert? All psychotherapists effectively prescribe themselves and, while we have long recognized the phenomenon of nonspecific and placebo effects, we doubt whether their impact is sufficiently appreciated.

 reviewed studies of sham surgeries for patients with Parkinson disease, knee surgery, and angina pectoris and rejected the view that placebo treatments are, by definition, inert. As a component of psychotherapy, they provide the integral, curative, nonspecific that may actually activate spontaneous remission and may provide ongoing benefits. We should not be dismissive of these types of effects and should realize that the term “placebo effect” does not capture the reality that optimal, nonspecific, therapeutic ingredients are powerful and not, in fact, inert. We also need to recognize the distinct contribution of placebo effect in RCTs, which makes clarification of the specific effects of each therapy more difficult, especially for the psychotherapies. This issue should be embraced in study designs rather than ignored or summarily dismissed.

The third methodological issue relevant to psychotherapy efficacy research concerns underestimation of the role of therapeutic allegiance. Allegiance is not only strongly associated with outcome (with effect sizes of up to 0.65), but it may also equalize treatment differences.

Meta-analyses have attributed almost one-third of the variance in effect sizes to therapeutic allegiance, and therapeutic allegiance also accounts for 69% of the variance in outcome.

 On the basis of these results, others have quantified that 92.5% of the time therapeutic allegiance alone may predict the treatment that will be most successful.

Studies that position CBT and IPT as first-line treatments for depression rarely consider this factor.

Universal application of treatments across nonspecific disorders

We are not suggesting that CBT, IPT, or antidepressant drugs are ineffective treatments for major depression-despite their minimal separation from placebo/control therapies in RCTs. Rather, we wish to argue that their specific efficacy has not been established. The obfuscating problem rises from diagnoses such as major depression and dysthymia that are no more than domain names (like major breathlessness) that subsume multiple depressive conditions (with variable biological, psychological, and social causes) and yet are the categorical diagnoses used in RCTs for antidepressants and psychotherapies.

Imagine if a new and very effective anti-asthma drug was tested in a placebo-controlled trial for those with major breathlessness, but only 5% to 10% of the participants actually had asthma. The risk is that the truly effective anti-asthma drug would not emerge as superior to placebo. In essence, because the methodological approach was logically flawed, logically flawed interpretations follow. Similarly, physicians would not tell their patients that they have diabetes and merely decide treatment on that domain diagnosis alone. Rather, patients would have their diabetes subtyped-with a diagnosis of type 1 diabetes treated with insulin and a type 2 diabetes diagnosis addressed with lifestyle changes.

Thus, we argue for abandoning the current nonspecific model that allows treatments to be tested as if they have a nonspecific application for nonspecific disorder categories because this invariably produces nonspecific results.

 Clinical depression is not an entity; it comprises a heterogeneous collection of different conditions that have their own propensities to preferentially respond to drugs and/or psychotherapeutic approaches.

By simply adopting a domain diagnosis of major depression, the true treatment validity of CBT and IPT is obscured. Although we acknowledge that CBT and IPT are likely to be specifically effective in some circumstances, the evidence is yet to be demonstrated and will not be until context-specific clinical syndrome RCTs are undertaken that respect the intrinsic rationale of the specific therapeutic approach. The task is to identify when antidepressant drugs, CBT, IPT, and other therapies are primary and salient in addressing causes and when and if they complement each other, as well as when they might best be operationalized sequentially. “

We have outlined several reasons why the evidence-based treatments for depression have been falsely positioned as first-line treatments for depression and why the actual evidence of their effectiveness is compromised by faulty diagnostic paradigms and RCT design strategies. Current clinical management of the depressive disorders risks the affective fallacy-evaluating a work by its effects on the reader rather than by the integral strengths of the work itself.

In this context, the choice between different treatments for each patient often risks resting simply on the professional and personal biases of the patient and therapist. As it currently stands, the literature gives CBT and IPT high-cachet status and risks overselling them as treatments for depression.

There is strong clinical support for the 3 ESTs considered here, and we do not judge antidepressant drugs, CBT, or IPT as ineffective in the sense of acting only as placebos. However, we do not view any one as having universal relevance or application. That is theoretically nonsensical and, unfortunately, so plays out in the clinical arena. The priority is to not view any therapy as having universal application for clinical depression, to respect a “horses for courses” model, and to determine the specific contribution of different treatments to different conditions.

Gordon Parker, AO, MBBS, MD, PhD, DSc
Scientia Professor of Psychiatry
University of New South Wales
Executive Director, Black Dog Institute
Prince of Wales Hospital
Randwick, NSW, Australia

Kathryn Fletcher
Research Assistant, Black Dog Institute

Professor Parker and Ms Fletcher report that they have no conflicts of interest concerning the subject matter of this article.

 Kirsch I, Deacon BJ, Huedo-Medina TB, et al. Initial severity and antidepressant benefits: a meta-analysis of data submitted to the Food and Drug Administration. 

 Parker G, Roy K, Eyers K. Cognitive behavior therapy for depression? Choose horses for courses. 

 Parker G, Parker I, Brotchie H, Stuart S. Interpersonal psychotherapy for depression? The need to define its ecological niche. 

Manufacturing Depression: The Secret History of a Modern Disease

Parker G, Fletcher K. Treating depression with the evidence-based psychotherapies: a critique of the evidence. 

 Wampold BE, Minami T, Baskin TW, Callen Tierney S. A meta-(re)analysis of the effects of cognitive therapy versus ‘other therapies’ for depression. 

 Cuijpers P, Geraedts AS, van Oppen P, et al. Interpersonal psychotherapy for depression: a meta-analysis. 

 Westen D, Novotny CM, Thompson-Brenner H. EBP ≠ EST: Reply to Crits-Christoph et al. (2005) and Weisz et al. (2005). 

The Great Psychotherapy Debate: Models, Methods, and Findings

. Mahwah, NJ: Lawrence Erlbaum Associates; 2001.


 Jacobson NS, Dobson KS, Truax PA, et al. A component analysis of cognitive-behavioral treatment for depression. 

 Ilardi SS, Craighead WE. The role of nonspecific factors in cognitive-behavior therapy for depression. 

 Frank JD. Common features of psychotherapy. 

 Lambert MJ. Implications of outcome research for psychotherapy integration. In: Norcross JC, Goldstein MR, eds. 

The Emperor’s New Drugs: Exploding the Antidepressant Myth

 Luborsky JL, Barrett MS. What else materially influences what is represented and published as evidence? In: Norcross JC, Beutler LE, Levant RF, eds. 

Evidence-Based Practices in Mental Health: Debate and Dialogue on the Fundamental Questions

. Washington, DC: American Psychological Association Press; 2005:257-267.


 Robinson LA, Berman JS, Neimeyer RA. Psychotherapy for the treatment of depression: a comprehensive review of controlled outcome research. 

 Luborsky L, Diguer L, Seligman DA, et al. The researcher’s own therapy allegiances: a “wild card” in comparisons of treatment efficacy. 

 Westen D, Novotny CM, Thompson-Brenner H. The empirical status of empirically supported psychotherapies: assumptions, findings, and reporting in controlled clinical trials. 

 Paul GL. Strategy of outcome research in psychotherapy. 

(See Counterpoint by Steven D. Hollon, PhD)

Is Specificity Relevant When Treating Depression With Evidence-Based Treatments?

 argue that specificity has yet to be established for cognitive-behavioral therapy (CBT) or interpersonal psychotherapy (IPT)-the two psychosocial interventions most often touted as evidence-based treatments for depression. I agree with some of the points the authors make, but I disagree with others.

First, a distinction needs to be made between specificity and superiority. I agree with Parker and Fletcher (and Wampold before them) that nonspecific psychotherapy controls are hard to implement in a convincing manner. To the extent that is true, then finding a psychosocial intervention superior to a nonspecific psychosocial control could simply reflect a more powerful mobilization of those nonspecific factors (“my nonspecifics are bigger than your nonspecifics”). Therefore, one could find superiority in the absence of specificity.

The same concern can be raised with respect to comparisons between psychotherapies. As Parker and Fletcher also point out (and Luborsky before them), allegiance effects loom large in the treatment literature and account for much of the variance in outcomes. To the extent that allegiance effects reflect differences in enthusiasm for one approach over the other, then one could again find superiority in the absence of specificity. However, differential allegiance could also reflect differences in competence to implement the respective interventions.

 Such comparisons depend on the capacity of the research team to implement each of the respective interventions in a competent fashion, and it is rare that any one research group is competent to implement multiple psychotherapies in the same trial.

These concerns do not extend to pill-placebo controls in the context of comparisons to medications, since such controls can be implemented in a blinded and relatively unbiased fashion and medication efficacy depends less on the skill of the provider than on the dosage provided. Most such trials have found psychotherapy, including CBT for more severe or atypical depression, IPT or behavioral activation (BA) for more severe depression, and problem-solving therapy in general practice, to be superior to placebo and comparable to antidepressant medications.

CBT was no better than pill-placebo and less effective than antidepressants in patients with more severe depression in the studies by Elkin and associates5 and Dimidjian and colleagues.

 However, questions can be raised about the quality with which CBT was implemented in the first study and the role of allegiance effects in the second (the Dimidjian study was conducted at the home of BA).

Results with dynamic psychotherapy did not differ from those with pill-placebo in the only such comparison to date, but neither did antidepressant medication and the two psychotherapies differ.

 Other types of psychotherapies have yet to be compared with antidepressants.

What these studies suggest in aggregate is that CBT, IPT, and perhaps BA may have specific effects when competently implemented, but only for patients with more severe depression. In fact, among studies that tested for moderation with respect to severity, specific effects were found only among patients with more severe depression, with respect to both psychotherapy and medications.

 The latter is the “dirty little secret” of a pharmaceutical industry that has long selectively screened out patients with less severe depression (in order to up the odds of finding drug-placebo differences required to win FDA approval) and then turns around and markets those same medications to people who it knows full well are likely to respond for purely psychological reasons.

What all this means is that nonspecific factors are likely to be sufficient to produce response in most patients with less severe depression (the majority of patients with major depressive disorder) and that treatments with specific effects are required for only those patients with more severe (and possibly chronic or comorbid) depression. Virtually every psychosocial intervention that has been tested has been shown to be better than its absence, and Parker and Fletcher are correct that meta-analytic reviews suggest that differences are few among them and that nonspecific factors account for the largest portion of the change.

 When practice guidelines privilege CBT and IPT in their recommendations, it is because they have been tested more extensively and against more rigorous comparators, such as medication treatment, not because they have been shown to be superior to other types of psychotherapies in head-to-head comparisons.

Two other factors that likely influence guideline recommendations that Parker and Fletcher do not address are the greater breadth of effect shown by IPT and the more enduring effects shown by CBT relative to medications. There are indications that IPT is not only as effective as antidepressants in reducing acute distress but is also better at addressing relationship problems.

 CBT and perhaps BA have enduring effects not found for antidepressant medications that protect against relapse following treatment termination.

 Parker and Fletcher do not address these benefits, but rather treatment guidelines.

Absence of evidence is not evidence of absence. Just because something has not been tested does not mean that it does not work. However, when third parties are making decisions regarding treatment selection, absence of evidence is tantamount to absence of ticket. Guideline generators and policy makers look to the preponderance of the evidence. CBT and IPT have the most good-quality evidence of any of the existing psychotherapies to support their utility. This does not necessarily mean that their specificity (with respect to common factors) has been established (although the placebo-controlled trials certainly speak to that issue) or that their superiority to other psychotherapies has been established as well.

When other psychotherapies are not recommended by guidelines or selected by third-party payers, it is not because they have failed in direct comparisons with CBT or IPT (by and large those comparisons do not exist) but because they have not been tested as often or as stringently. Parker and Fletcher are right to call attention to that fact and it would be unwise to overstate the case for CBT or IPT (or especially BA, which has yet to be extensively tested). At the same time, it is not unreasonable for the recent guidelines to have greater confidence in CBT or IPT than they do for other approaches.

Steven D. Hollon, PhD
Professor
Department of Psychology
Vanderbilt University
Nashville, Tenn

Dr Hollon reports that he is the recipient of the NIH/NIMH P01 MH60713 grant.

 Parker G, Fletcher K. Treating depression with the evidence-based psychotherapies: a critique of the evidence. 

 Leykin Y, DeRubeis RJ. Allegiance in psychotherapy outcome research: separating association from bias. 

 DeRubeis RJ, Hollon SD, Amsterdam JD, et al. Cognitive therapy vs medications in the treatment of moderate to severe depression. 

 Jarrett RB, Schaffer M, McIntire D, et al. Treatment of atypical depression with cognitive therapy or phenelzine: a double-blind, placebo-controlled trial. 

 Elkin I, Shea MT, Watkins JT, et al. National Institute of Mental Health Treatment of Depression Collaborative Research Program. General effectiveness of treatments. 

 Dimidjian S, Hollon SD, Dobson KS, et al. Behavioral activation, cognitive therapy, and antidepressant medication in the acute treatment of major depression. 

 Mynors-Wallace LM, Gath DH, Lloyd-Thomas AR, Tomlinson D. Randomized controlled trial comparing problem solving treatment with amitriptyline and placebo for major depression in primary care. 

 Jacobson NS, Hollon SD. Prospects for future comparisons between drugs and psychotherapy: lessons from the CBT-versus-pharmacotherapy exchange. 

 Barber JP, Barrett M, Gallop R, et al. Short-term psychodynamic therapy vs. pharmacotherapy for major depressive disorders: the role of minority status and gender. 

 Driessen E, Cuijpers P, Hollon SD, Dekker JJ. Does pretreatment severity moderate the efficacy of psychological treatment of adult outpatient depression? A meta-analysis. 

 Fournier JC, DeRubeis RJ, Hollon SD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. 

 Khan A, Leventhal RM, Khan SR, Brown WA. Severity of depression and response to antidepressants and placebo: an analysis of the Food and Drug Administration database. 

The Emperor’s New Drugs: Exploding the Antidepressant Myth.

 Cuijpers P, van Straten A, Warmerdam L, Smits N. Characteristics of effective psychological treatments of depression: a metaregression analysis. 

 Cuijpers P, van Straten A, Andersson G, van Oppen P. Psychotherapy for depression in adults: a meta-analysis of comparative outcome studies. 

 Weissman MM, Klerman GL, Paykel ES, et al. Treatment effects on the social adjustment of depressed patients. 

 Weissman MM, Klerman GL, Prusoff BA, et al. Depressed outpatients. Results one year after treatment with drugs and/or interpersonal psychotherapy. 

 Dobson KS, Hollon SD, Dimidjian S, et al. Randomized trial of behavioral activation, cognitive therapy, and antidepressant medication in the prevention of relapse and recurrence in major depression. 

 Hollon SD, DeRubeis RJ, Shelton RC, et al. Prevention of relapse following cognitive therapy vs medications in moderate to severe depression. 

Cognitive-behavioral therapy, interpersonal psychotherapy, or antidepressants can be effective treatments for major depression-despite their minimal separation from placebo/control therapies in clinical trials. This article argues that their specific efficacy has not been established.

Debate: What’s the Evidence for the Evidence-Based Treatments of Depression?

The findings sounded like good news. As reported recently in 

chronic fatigue syndrome (CFS) may be successfully treated with a combination of psychotherapy and exercise. Specifically, results of a randomized trial showed that cognitive-behavioral therapy and graded exercise therapy have a moderate effect in the treatment of CFS.

 suggested that the study results “. . . are certain to displease many patients and to intensify a fierce, long-running debate about what causes the illness and how to treat it.” The 

 noted that “many patients . . . believe the 

 may be caused by viruses related to mouse leukemia viruses, and they are clamoring for access to antiretroviral drugs. . . .” Furthermore, “. . . the new study . . . is expected to lend ammunition to those who think the 

 is primarily psychological or related to stress [italics added].”

For those of us accustomed to the charge that psychiatry is trying to “medicalize normality”-and that “psychiatry has no objective tests” to validate our disease categories-this report is both ironic and revealing. First, it suggests that 

-not just physicians-may sometimes have compelling reasons for applying the “medical model” to conditions whose etiology and pathophysiology remain controversial and obscure. Indeed, in light of the serious adverse effects associated with antiretroviral drugs, it is extraordinary that some patients would be clamoring for these agents, given the tenuous link between CFS and a viral etiology. I suspect this speaks to the profound lethargy and physical impairment experienced by some patients with severe forms of CFS-and this, in turn, speaks to an important truth regarding the nature of what we call 

 “Disease” (disease) is usually first recognized by those who suffer with it, and by their loved ones. It is not fundamentally a scientific term, but an

Those who suffer with CFS understand this, and their predicament serves as a window into the conceptual and semantic problems that bedevil psychiatry.

report by David Tuller presents a microcosm of the linguistic ferment in the realm of medical nosology. Note that the reporter uses 3 different terms to describe CFS: 

This alone should tell us that in the matter of describing and classifying abnormal physical and emotional states, confusion abounds-and not just among journalists. Physicians and researchers, too, often bandy about terms such as “illness,” “syndrome,” and “disease” without much reflection as to the precise meaning of these terms, or how they differ from one another.

The  Platonic enterprise of “carving Nature at its joints” is wasted  surgery, if we are not relieving the suffering and incapacity of our  patients.

It is notable that despite a lack of reliable biomarkers or “lab tests” for CFS, the CDC describes CFS as a “distinct disorder with specific symptoms and physical signs.”

 Here we meet yet another poorly defined term: 

-the term of choice for conditions in the DSMs, and one that strikes some of us as a bit of a dodge. How, after all, does a 

? If it is simply a matter of identifiable pathophysiology, then why is Alzheimer disease listed as a cognitive “disorder” in DSM-IV? Are we to infer that all “diseases” are also “disorders,” but that the converse is not true? It is enough to make the clinician’s eyes glaze over.

It is not merely intellectual laziness that underlies this unsavory stew of disease terms, although some-times that charge may apply. In truth, we physicians are, by and large, practical folk. We see our waiting rooms crowded with fellow human beings in various states of pain, suffering, and incapacity. We want to help them as efficiently and effectively as possible, and we don’t care very much, at the end of the day, whether we have alleviated a syndrome, an illness, a disease, or a disorder-and neither does the patient. We 

 care a great deal that the patient who came in feeling miserable leaves feeling better. We engage in a daily struggle to reduce the net amount of medical 

 in the world-not to win prizes as philosophers of science or language.

Unfortunately, in recent years, some scholars and researchers have been fixated on the precise boundaries of mental “normality” and “abnormality”-as if Nature itself recognizes this neat dichotomy! To be sure, many of us-including this writer-have pointed to instances in which a condition has been prematurely or inappropriately labeled a “mental disorder.” For example, I have argued against including conditions such as “pathological bigotry” and “Internet addiction” in DSM-5, and I have raised serious questions regarding the validity of so-called hypoactive sexual desire disorder.

Others have gone much further in their critique of psychiatric nosology, declaring some psychiatrists guilty of “disease-mongering” or pointing to the danger of diagnostic “fads” in psychiatry.

 (Recently, Dr Allen Frances directed me to an 

, discussing the medical treatment of “excessive and annoying cheerfulness!”

Part of our preoccupation with the boundaries of normality and abnormality lies in our failure to produce “a model of mental disorder,” as Dr Niall McLaren

 recently argued. Indeed, I believe psychiatry has been hobbled by the very terms now emblazoned on our DSMs: “mental” and “disorder.” Neither of these terms has been satisfactorily defined, and neither has been very helpful. I would much rather see a classification of “neuropsychiatric disease” or “brain-mediated disease.”

 More centrally, however, I believe we have gotten lost in the “trees” of boundary issues, while failing to see the “forest” of our patients’ chief concern:

 the relief of their suffering and incapacity; that is, the relief of disease

 (disease). I believe it is from this experiential wellspring that our nosology should issue. This same reality also defines our profession’s chief 

the relief of medically based suffering and incapacity by any safe and effective means.

 In short, I am arguing that our nosology must be firmly rooted in our 

Even our diagnostic criteria should follow this ethical imperative. Thus, rather than focusing primarily on 

-achieved when a set of diagnostic criteria is based on an identifiable pathogenic agent or process-I believe we should be focusing on what I have called 

 the extent to which our diagnostic criteria 

enable us to reduce the patient’s particular type of suffering and incapacity.

 I do not draw a sharp distinction between “validity” and clinical “utility.”) We can gradually refine our prototypical disease categories, based on how well their criteria hold up in empirical studies of treatment; ie, the more the category criteria facilitate effective treatment, the higher their instrumental validity. Only secondarily should our disease categories be modified by other types of validity, such as 

 (Discriminant validity is essentially the degree to which the criteria can identify one construct, such as “narcissism,” without demonstrating a high correlation with an unrelated construct, such as “schizotypy.”

So, how does all this apply to CFS and the insistence by some that patients with CFS be treated with antiretroviral drugs? It would be unfair to conclude that those advocating this position are trying to “medicalize” severe, chronic fatigue, in any pejorative sense of the term “medicalize.” On the contrary: like physicians, these advocates are, in good faith, trying to 

-and they have every right to do so, regardless of how well or poorly we understand the pathophysiology of CFS. Of course, it is an empirical question as to whether antiretroviral drugs are either safe or effective in CFS. I have serious doubts, but only clinical investigation will resolve the matter. Nonetheless, there should be no quarrel over the reality of severe CFS as an instantiation of genuine 

 just as schizophrenia and major depression constitute real disease.

In my view, psychiatrists would do well to avoid scholastic disputations over “where to draw the line” between normality and abnormality.

(If 99 in 100 stockbrokers jump out the window after the stock market crashes, is that behavior “normal” or “abnormal”?) So, too, with our nosology. The Platonic enterprise of “carving Nature at its joints” is wasted surgery, if we are not relieving the suffering and incapacity of our patients. This applies whether we are discussing major depressive symptoms following bereavement

 or severe, chronic fatigue. The central question for both our psychiatric nosology and our medical duty is just this: how much suffering and incapacity is burdening the patient who seeks our help? If the answer is, “Quite a lot,” then our patient has bona fide 

, and it is ethically incumbent on us to provide safe and effective treatment.

 White PD, Goldsmith KA, Johnson AL, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial.

 Tuller D. Researchers say psychotherapy eases chronic fatigue, a finding unlikely to satisfy. 

http://www.nytimes.com/2011/02/18/health/research/18fatigue.html?_r=1

 Pies R. What should count as a mental disorder in DSM-5? 

http://www.psychiatrictimes.com/dissociative-identity/content/article/10168/1402032

 Pubmed Health. Chronic Fatigue Syndrome. 

http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002836

http://www.psychiatrictimes.com/display/article/10168/55226

 Pies R. Should DSM-V designate “internet addiction” a mental disorder? 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2719452

 Pies RW. FDA lacks desire for flibanserin-but does hypoactive sexual desire disorder even exist? 

 http://www.psychiatrictimes.com/sexual-disorders/content/article/10168/1632801

 Healy D. The latest mania: selling bipolar dis-order. 

 2006;3:e185. doi:10.1371/journal.pmed.0030185. http://www.plosmedicine.org/article/metrics/info%3Adoi%2F10.1371%2Fjournal.pmed.0030185;jsessionid=02A5A6715DC868BFDABF4DFD33E1EAFA.ambra02. Accessed March 12, 2011.


 Frances A. Normality is an endangered species: psychiatric fads and overdiagnosis. 

http://www.psychiatrictimes.com/dsm-5/content/article/10168/1598676

 FDA approves depressant drug for the annoyingly cheerful. 

http://www.youtube.com/watch?v=_et969pc7iA

 McLaren N. Temper tantrums, mental disorder, and DSM-5: the case for caution. 

http://www.psychiatrictimes.com/blog/dsm-5/content/article/10168/1803237

 Pies R. The ideal and the real: how does psychiatry escape The DSM-5 “fly-bottle”? 

Bulletin of the Association for the Advancement of Philosophy and Psychiatry.

http://alien.dowling.edu/~cperring/aapp/bulletin_v_17_2/Vol17N2.pdf

 There should be no quarrel over the reality of severe CFS as an instantiation of genuine disease, just as schizophrenia and major depression constitute real disease.