Popular Posts

Total Downloads Worldwide

Monday, 22 July 2013

PSYCHIATRY DEBATE POST DSM-5 : Clinical judgment in psychiatry. Requiem or reveille? GIOVANNI A. FAVA - COURTESY OF THE informahealthcare.com website


Clinical judgment in psychiatry.
Requiem or reveille?


Fava GA. Clinical judgment in psychiatry. Requiem or reveille? Nord J Psychiatry 2013;67:1–10.


There is increasing awareness of a crisis in psychiatric research and practice.

Psychopathology and clinical judgment are often discarded as non-scientific and obsolete methods. Yet, in their everyday practice, psychiatrists use observation, description and

classification, test explanatory hypotheses, and formulate clinical decisions.


: The aim of this review was to examine the clinical judgment in psychiatry, with special reference to clinimetrics, a domain concerned with the measurement of clinical phenomena that do not find room in customary taxonomy.


: A MEDLINE search from inception to August 2011

using the keywords “ clinical judgment ” and “ clinimetric ” in relation to psychiatric illness for articles in English language was performed. It was supplemented by a manual search of the

literature. Choice of items was based on their established or  potential incremental increase inclinical information compared with use of standard diagnostic criteria. The most representative examples were selected.


: Research on clinical judgment has disclosed several innovative

assessment strategies: the use of diagnostic transfer stations instead of diagnostic endpoints using repeated assessments, subtyping versus integration of different diagnostic categories,

staging, macro-analysis, extension of clinical information beyond symptomatic features.

Evidence-based medicine does not appear to provide an adequate scientific background for challenges of clinical practice in psychiatry and needs to be integrated with clinical judgment.


. A renewed interest in clinical judgment may yield substantial advances in clinical assessment and treatment. A different clinical psychiatry is available and can be practiced now.

• Clinical judgment, Clinimetrics, Evidence-based medicine, Conflict of interest, Mental disorders.
Giovanni A. Fava, M.D., Department of Psychology, Viale Berti Pichat 5, 40127 Bologna, Italy,

E-mail: giovanniandrea.fava@unibo.it; Accepted 7 June 2012.

George Engel 
(1) differentiated between “ scientific physicians ” (clinicians who fully apply the scientific method in their care of patients and in their understanding of the disease) and “ physician-scientists ” (physicians whose primary commitment is to scientific research pertaining to medicine and who have little or no familiarity with the clinical process). Clinical practice is the

source of fundamental scientific challenges for scientific

physicians, whereas the application of basic (including

pharmaceutical) research is the preferred focus of

physician-scientists. Part of the challenge and, at the

same time, fascination of being a clinician lies in applying

scientific methods in the care of patients and in under-

standing disease (2). Greater knowledge should result in

significant benefits for the patients, and in a sense of

continued development on the part of the physician. We

are witnessing, however, a progressive detachment of

clinicians from research, which is often accompanied

by a sense of personal stagnation and tiredness (2).

This detachment is mainly the reflection of an intellectual

crisis that became more and more manifest in recent

years (1 – 3). Psychiatrists are constantly reminded that

genetics and neurosciences are going to transform and

improve their practice. Biomarkers are considered the

stairway to such a shift (4) and leading journals, such as

the American Journal of Psychiatry and the Archives

of General Psychiatry, are pursuing this perspective.

Psychiatrists may share this optimism and wait for this

event. Nothing has really come in the past two decades

(5, 6), as exemplified by the field of psychiatric genetics

(7), but we may be really close. Psychopathology

and clinical judgment are discarded as non-scientific

and obsolete methods. Yet, in their everyday practice,

psychiatrists use observation, description and classification, test explanatory hypotheses, and formulate clinical decisions. In evaluating whether a patient needs admission to the hospital (or can be discharged from it), in deciding whether a patient needs treatment (and in case what type) and in planning the schedule of follow-up visits or interventions, the psychiatrist uses nothing more.

When, in the early 1990s, these mechanisms became operational in psychiatry, there were several important obstacles: the  presence of independent studies that could challenge sponsored indings, the potential influence of uncontrolled review articles and opinions by scientific physicians, the stubborn reliance of psychiatrists on clinical judgment despite evidence-based medicine, and the type of clinical research that was performed.

All four aspects were taken care of and the clinician who wanted to retain a cautious and balanced attitude felt

like the person whom Chomsky depicts as sitting alone

in front of the TV, thinking he/she must be crazy or out-

dated for not buying what comes out of the tube (13).

The pseudoscience of meta-analyses

In the mid-1990s, Alvan R. Feinstein (14) compared

meta-analyses to the alchemy that existed before modern

scientific chemistry. The analogy was the hope to con-

vert existing things into something better (changing base metals into gold) and the work with material that was heterogeneous  and poorly identified. Mixingtogether studies of different qualities and characteristics could only lead to violation of scientific principles of precision and homogeneity. It is a common belief that meta-analyses provide an objective appraisal of the state of the art in a specific field. Actually,  during thedevelopments of these analyses, there are many steps

that may involve highly subjective choices (14 – 16): formulation of the question, collection of studies (published

versus unpublished, databases, key-words, etc.), criteria

for eligibility and selection of studies, evaluation of

risk of bias, methods of data extraction and analysis,

choice of assessment criteria, presentation of results and

interpretation of data. All these issues may be affected

by conflict of interest (16). However, authors of meta-

analyses are only required to disclose their financial

interests and are unlikely to detail the source of funding

of the studies that were included (16).

The example of benzodiazepines

A recent meta-analysis that was concerned with drug

treatment of generalized anxiety disorder (17) provides

an illustration of how conflict of interest may affect the

rocess. A pharmaceutical firm conceptualized and

designed the study, and commissioned two of the authors,

who work in a private medical communications company,

to conduct the systematic review and meta-analysis, and

prepare the manuscript. Two other authors, who were

university employees, performed a critical review of the

results and assisted in the development of the manuscript.

The study was allegedly independent, yet all authors had

financial ties to the funding firm and other pharmaceuti-

cal companies that manufactured drugs that were included

and discussed in the meta-analysis. The expert who was

commissioned to write the accompanying editorial (18)

than the science of psychopathology (8) and clinical

judgment (9).

The proliferating connections between scientists and

the industry, with ensuing conflicts of interests, have

brought the credibility of clinical medicine into a crisis

(10). Not surprisingly, in view of its characteristics, psy-

chiatry has been particularly vulnerable to this loss of

credibility (11, 12). Corporate interest has resulted in self-

selected academic oligarchies (special interest groups) that

influence clinical and scientific information (10). Members

of special interest groups, by virtue of their financial

power and close ties with other members of the group,

have the task of systematically preventing dissemination

of data that may be in conflict with their interests. The

first target is to undermine the critical individual judgment

of the physicians. The intellectual freedom portrayed by

scientific physicians, in particular, is the worst enemy of

special interest groups, and thus required massive doses

of censorship. Censorship may take different forms:

direct suppression of information by special interest groups

who act as editors and reviewers or make choices in scientific programs; careful selection of the literature in a

biased direction and manipulated interpretation of clinical

trials (including those supported by public sources); self-

censorship (when an investigator omits of raising ques-

tions and criticism for the fear of retaliation) (10).

Not all conflicts of interest in psychiatry are of a

financial nature (personal recognition, career advance-

ment, visibility in the media, favoring a friend or relative,

the allegiance to a school of thought, political commitment, rivalry between experts, representation of a certain

professional society, involvement in specific educational

activities). However, the conflicts concerned with financial matters have achieved prominence in the past decade

and have endangered a pluralism that existed before (10).

In this review, the detrimental effects of pharmaceutical psychiatry on shaping clinical orientations of physi-

cians and how clinical research concerned with clinical

judgment and new political attitudes may foster a renais-

sance of psychiatry as a medical discipline are examined.

Evidence-based medicine and clinical judgment

Chomsky ’ s (13) mechanisms of propaganda may apply to

what has occurred in medicine in the past two decades.

Corporate interests have fused with academic medicine to

create an unhealthy alliance that works against objective

reporting of clinical research (censorship), sets up meetings and symposia with the specific purpose of selling

the participants to the sponsors (engineering opinions),

gets its prodigal experts into leading role in journals,

medical associations and non-profit research organizations

(using the public relations industry), and provides the

appropriate degree of retaliation to outliers (marginalizing

with increasingly complicated and cumbersome procedures

that require a working team (25). Detailing literature

searches and getting as close as possible to a comprehensive  coverage of the literature are of course welcome targets, even  though these procedures were generallyendorsed by traditional reviews (disdainfully tagged as “ narrative ” ). However, this does not necessarily occur with systematic reviews, as the following personal example concerned with bipolar disorder outlines.

Reviews on bipolar disorder

When Robert Kellner and I published a review on

prodromal symptoms of affective disorders, including

bipolar disorder (26), I had gone through the literature

both with a computerized (Medline) and manual search,

including the heavy volumes of the Index Medicus and

discussed all the issues with my co-author. I had person-

ally interviewed the patients in a specific study on pro-

dromes of bipolar disorder (27). The conclusion was that

there was high interindividual variability between patients,

which did not allow recognition of a specific prodromal

phase (26). However, prodromal symptoms tended to be

consistent within the same individual, i.e. an affective epi-

sode tended to begin in the same way for the same patient

and this allowed room for early intervention. Indeed, years

later a randomized controlled trial demonstrated the feasibility of this approach (28), which was further confirmed

by subsequent trials concerned with psycho-education (29).

I updated the review in 1999 (30); there was no substantial change in conclusions compared with 1991, as well as

it was found to be the case in an independent review that

appeared in 2003 (31), but other implications were added.

In 2010 (32) and 2011 (33), two systematic reviews on

prodromes of bipolar disorder were published. The first

paper (32) failed to cite previous reviews (26, 30), but

even more importantly, did not include the investigations

that were discussed in those reviews. The conclusion was

typical of current systematic reviews: “ More well-designed

in-depth studies, including qualitative ones, are needed

to characterize the initial bipolar prodrome ” (32, p. 126).

The same omissions took place in the other paper (33),

despite the fact that one of the missing reviews had been

published in the same journal (30). The authors of this

2011 paper (33) identified specific clinical features preced-

ing bipolar disorder and ventured in postulating primary

and secondary interventions. A note of caution was of

course added: “ Large-scale longitudinal studies are needed

to validate these features and characterize their specificity

and sensitivity in independent samples ” (33, p. 1567).

I wish these authors were simply aware of what had

actually been published before advocating new studies.

Systematic or critical reviews?

I am afraid that cumbersome instructions that require a

large team of authors (six in the 2011 review) do not also had financial ties with a number of the pharmaceutical companies that manufactured drugs that were included and discussed in  the meta-analysis. A systematic review of randomized controlled drug trials was performed and,by use of probabilistic mixed-treatment meta-analysis, concluded that two antidepressant drugs had advantages over other treatments in generalized anxiety disorder.

These conclusions were challenged by an editorial that

appeared in another journal (19). Trials were selected if

they could allow determination of “ response ” (the proportion of patients who experienced a reduction of at least 50% of their baseline score on the Hamilton Anxiety Rating Scale) and remission (the proportion of patients below a certain cut-off on the scale). The authors failed to justify the choice of outcome measures, which has the major disadvantage of being affected by different characteristics of trials, maximizing the systematic tendency of meta-analyses to violate the internal validity of

the placebo comparison. The procedure excluded a great

number of investigations concerned with older and low-

cost medications, such as benzodiazepines, despite a large

body of evidence pointing to their efficacy in generalized

anxiety disorder (19). Berney et al. (20) reviewed of controlled trials on anxiety disorders that compared antidepressant drugs with benzodiazepines and could identify only one trial with fewer antidepressants. They concluded that the major change of prescribing patterns from benzodiazepines to newer antidepressants in anxiety disorders occurred without any comparative evidence (20). A major drive in the change was the risk of dependence with benzodiazepines, even though withdrawal symptoms frequently occur with newer antidepressants upon tapering and discontinuation (21), even in optimal conditions, and do not necessarily subside within a few weeks (22).

The weight of meta-analyses

As often happens with innovations, the weight given to

meta-analyses is likely to be reconsidered in due course:

statistically significant meta-analyses of clinical trials have

been found to have modest credibility and inflated effects

(23). Clinical reviews which focus on the methodological

appraisal of individual studies and their clinical integration in practice tend to be regarded as less “ scientific ”

than meta-analyses, whereas just the opposite is true (14).

Combining heterogeneous studies in meta-analyses may

only lead to inconclusive results (24) and negative treatment trials tend to go unpublished despite registration (16). Careful analyses of individual studies, with appropriate mention to confl

m ict of interest issues, are the actualbest-evidence syntheses.

The intellectual poverty of systematic reviews

The traditional review article with one or two experts

who review the literature drawing from their clinical

experience tends to be substituted by systematic reviews,

aimed at overshadowing truly independent and high-

quality individual studies. Familiarity with the clinical

process and intellectual independence can make quite a

difference in the way the literature is examined.

Evidence-based medicine as Leitkultur

The concept of evidence-based medicine, from its incep-

tion in the early 1990s, has achieved wide currency

and enthusiastic endorsement in all areas of clinical medicine, including psychiatry. Feinstein & Horwitz (37)

were among the first to warn about the dangers of

excessive reliance on randomized controlled trials and meta-

analyses. An issue that is neglected is the fact that, when

transferred to clinical medicine from their origins in agricultural research, randomized trials were not intended to

answer questions about the treatment of individual patients

(37). The results may show comparative efficacy of treat-

ment for an average randomized patient, but not for perti-

nent subgroups formed by characteristics such as severity

of symptoms, comorbidity and other clinical nuances.

Feinstein & Horwitz (37) also warned against the authoritative aura given to collections of “ best available evidence ” , which may lead to major abuses that produce

inappropriate guidelines or doctrinaire dogmas for clinical

practice. The risk is particularly serious in view of the fact that financial conflicts of interest are substantial in

medical societies and guidelines authors (10, 38). This has

been found to apply also to the psychiatric field (39, 40).

Special interest groups are thus using evidence-based

medicine to enforce treatment through guidelines, advocating what can be subsumed under the German language term of “ Leitkultur ” , which connotes the cultural superiority of a culture, with policies of compulsory,cultural assimilation. In psychiatry, such process has achieved strong prescribing connotations (41), with a resulting neglect of psychosocial treatments.

As Healy (41) remarks, randomized placebo-controlled trials originated as efforts to debunk therapeutic claims, but the force field in which medicine is now practiced has transformed them

into technologies that mandate action ( ... ) Where the placebo arms of antidepressant, antipsychotic or mood stabilizer trials suggest we should not be using the drugs as readily as we do, the trials of these products, embodied in guidelines, have instead become a means to enforce treatment. (41, p. 200)

Use of clinical judgment is thus viewed as a dangerous

departure from established patterns, instead of exercise

of critical thinking.

The inadequacy of current research designs

and strategies Elena Tomba (42) observed that the standard randomized controlled trial design is still based on the acute disease prevent major omissions that are functional to specific

hypotheses or end up to state that the evidence is too

limited and further studies are needed, as was found to

be the case in more than half of Cochrane reviews (34).

Laupacis & Straus (34) remark that the traditional review

has its virtues: the expert interprets research findings in

light of clinical experience and judgment, particularly

where the evidence is limited. If he/she distinguishes

between evidence and opinion, this approach can be

much more helpful to clinicians and policymakers.

The reliability of reports of studies funded by the

pharmaceutical industry has been seriously questioned

(10). Researchers with financial conflicts of interest are

more likely to publish articles (original investigations,

editorials, systematic and non-systematic reviews, meta-

analyses) that support the products of the companies with

which the researchers have financial ties (10). Simple dis-

closure of financial conflicts of interest is not regarded

as sufficient for original investigation funded by pharmaceutical companies, and strategies for minimizing biases

have been suggested, such as ensuring that at least one

author who is not employed by a commercial firm has

full access to all of the data and the use of an independent biostatistician (35). Surprisingly, however, little has

been proposed to minimize bias in other types of papers,

and particularly systematic reviews and meta-analyses

(16, 25, 35). When these latter papers have been supported by the industry, by means of funding or authors ’ties, they have been found to reach conclusions that favored sponsors ’ interests more than independent metaanalyses (16).

Journals policies and reviews

There is the need for a reassessment of journals ’ policies

concerned with this type of paper. In line with what has

been suggested for authors of clinical practice guidelines

(35), meta-analyses should only be conducted by investi-

gators free of substantial conflicts of interest (10). The

definition of conflict of interest can be, however, less

stringent than that endorsed by American professional

 medical societies (36). It can be suggested that a researcher meets the criteria for the presence of substantial conflict of interest when he/she is an employee of a private firm, and/or is a regular consultant or on the board of directors of a firm, and/or is a stockholder of a firm related to the field of research and/or owns a patent directly related to the published work (10). The threshold for determining conflict of interest is thus based on thecontinuity of a financial relationship with a private company. Occasional consultancies, grants for performing an

investigation, or receiving honoraria or refunds for

specific occasions would not be a source of substantial

conflict of interest. Rewarding those researchers who are

free from binding financial ties may avoid inappropriate

publication of reviews driven by financial incentives and

heterogeneous clinical phenomenon such as depression is

immense. But what is its translational value?

The reveille of clinical judgment

In 1967, Alvan Feinstein dedicated a monograph to an

analysis of clinical reasoning that underlies medical evaluations, such as the appraisal of symptoms, signs and

the timing of individual manifestations (52). In 1982, he

introduced the term “ clinimetrics ” (53) to indicate a

domain concerned with the measurement of clinical issues

that do not find room in customary clinical taxonomy.

Such issues include the types, severity and sequence of

symptoms; rate of progression in illness (staging); severity of comorbidity; problems of functional capacity; reasons for medical decisions (e.g. treatment choices), and many other aspects of daily life, such as well-being and distress (54, 55). The customary clinical taxonomy in psychiatry does not include patterns of symptoms, severity of illness, effects of comorbid conditions, timing of phenomena, rate of progression of illness, responses to previous treatments, and other clinical distinctions that demarcate major prognostic and therapeutic differences

among patients who otherwise seem to be deceptively

similar since they share the same psychiatric diagnosis

(56). Clinimetric research in psychiatry has yielded

important insights as to the role and function of clinical

judgment (56, 57).


A first strategy is concerned with staging. It differs from

the conventional diagnostic practice in that it defines not

only the extent of progression of a disorder at a particular point in time, but also where a person is currently along the continuum of the course of illness. Staging methods for unipolar depression, bipolar disorder, panic disorder and schizophrenia, which outlined the basic steps

of development of a psychiatric disorder, ranging from

the prodromal to the residual and chronic forms, in a

longitudinal view of development of disturbances, have

been developed (56, 58, 59), together with. specific

instruments (60, 61). In two randomized controlled trials

(62, 63), psychotherapeutic intervention was applied

according to a staging method and was found to yield

long-term benefits (64, 65).

Unitary concepts

A second approach involves building unitary concepts

from apparently scattered phenomena.

 Tyrer and associates (66) remarked that what is shared by syndromes such as anxiety, panic, phobic disturbances and irritability may be as important as the differences between them and conditions that are apparently comorbid could be part of thesame clinical syndrome. They argued that the combination of mixed anxiety and depressive disorders together

model and ideally evaluates therapeutic effects in

untreated patients who have a recent acute onset of their

disturbances. This is in sharp contrast with the fact that,

particularly in psychopharmacology, the patient is likely

to have experienced other treatments before and these

treatments may actually modify the course and responsiveness of the individual patient (21). Under ordinary conditions, patients are included in a trial regardless of

their treatment history. The heterogeneous features of

these that “ nowhere patients ” would then affect the outcome of the trial. Meta-analyses of these nowhere groups

of patients may amplify the heterogeneous nature of the

patient populations (19), particularly if random effects

models where endorsed (24) and trials had different rates

of participation (43). Moving from the Beatles (nowhere

patients) to the Talking Heads, we may add that

pathophysiological studies of these patient populations

end up being a “ road to nowhere ” . The progress of neurosciences in the past two decades has often led us to

believe that clinical problems in psychiatry were likely to

be ultimately solved by this approach. Such hopes are

understandable in terms of massive propaganda operated

by biotechnology corporations (44) and reaction to a long

prevalence of “ brainless ” approaches (45). An increasing

number of psychiatrists are wondering, however, why the

cures and clinical insights that neurosciences have promised have not taken place. Biological reductionism (2)

has resulted in an idealistic approach, which is quite far

from the explanatory pluralism required by clinical practice. Kendler (46), Van Praag (47) and Belmaker (48)

have been outspoken critics of this reductionism. Neurosciences have exported their conceptual framework into

psychiatry much more than serving as an investigative

tool for addressing the questions addressed by clinical


An example may be provided by the problems related

to the loss of clinical effects during long-term antidepressant treatment (21). The return of depressive symptoms during maintenance antidepressant treatment

was found to occur in 9 – 57% of published trials (49).

Pharmacological tolerance, loss of placebo effect,

increase in disease severity, change in disease pathogenesis, accumulation of a detrimental metabolite, unrecognized rapid cycling and prophylactic inefficacy have been

suggested as possible explanations (49). Psychosocial

factors, such as the role of life events in causing depressive relapse during maintenance treatment (50), have not

been considered. Also the literature on differential neurobiological effects of psychosocial treatments compared

with pharmacotherapy is scarce (51). There is virtually

no exploration of the neurobiological correlates of the

loss of clinical effects, despite its clinical importance and

the practical implications that research in this area would

entail (21). At the same time, the amount of research

attempting a neurobiological characterization of a highly

often subsumed under a rubric of the Diagnostic and

Statistical Manual of Mental Disorders (DSM) (80).

A single assessment generates the prognostic and thera-

peutic judgments of the clinician. A DSM diagnosis

(e.g. major depressive disorder), however, encompasses a

wide range of manifestations, comorbidity, seriousness,

prognosis and responses to treatment. The majority of

patients with mood and anxiety disorders do not qualify

for one, but for several axis I and axis II disorders (81).

Feinstein, when he introduced the concept of comor-

bidity, referred to any “ additional co-existing ailment ”

separate from the primary disease, even in the case this

secondary phenomenon does not qualify as a disease

per se (82). Indeed, in clinical medicine, the many meth-

ods that are available for measuring comorbidity are not

limited to disease entities (83). Unfortunately, in the

DSM comorbidity has been used only in reference to

additional diagnoses, and not to indicate significant problems, situations and subthreshold conditions.


A method has been developed in psychiatry for

organizing clinical data as variables in clinical reasoning. Emmelkamp et al. (84) have introduced the concept of macro-analysis (a relationship between co-occurring syndromes and

problems is established on the basis of where treatment

should commence in the first place) in anxiety disorders.

This method has been extended to mood disorders (56),

psychosomatic assessment (85) and drug dependence

(86). Macro-analysis starts from the assumption that

in most cases there are functional relationships with

other more or less clearly defined problem areas and that

the targets of treatment may vary during the course of

disturbances (56).

Diagnostic transfers

Feinstein (87) remarks that, when making a diagnosis,

thoughtful clinicians seldom leap from a clinical manifestation to a diagnostic endpoint. The clinical reasoning goes through a series of “ transfer stations ” , where potential

connections between presenting symptoms and pathophys-

iological process are drawn. These stations are a pause

for verification, or change to another direction (87). The

use of diagnostic transfer stations has been suggested

by the sequential treatment model (29, 88), an intensive,

two-stage approach, which includes the use of one

treatment (e.g. psychotherapy) after remission has been

achieved with another (e.g. pharmacotherapy). The

sequential model relies on repeated assessments (after

each line of treatment has been completed) that may

modify an initial diagnosis (e.g. pre-existing anxiety disturbances may emerge after pharmacotherapy of a major

depressive episode). It recognizes that for most patients a

single course of treatment is insufficient for yielding

adequate improvement and that different combined or

with a certain type of abnormal personality, constitute a

single syndrome, the general neurotic syndrome (66), in

line with the traditional concept of neurosis, in its phenomenological (67) and psychodynamic (68) traditions.

The syndrome was shown to be associated with a poor

response to treatment, frequent symptoms throughout the

neurotic diagnostic spectrum and tendency to relapse

(66). A related strategy deals with the concept of allo-

static load, the cumulative effects of stressful experiences

in daily life (69).


A complementary strategy has to do with subtyping and

differentiating within a diagnostic entity. The need for

subtyping major depressive disorder, since this category

is too broad to yield meaningful treatment implications,

has been recently underscored (70 – 72). The basic assumption is that clinical manifestations that share the diagnosis of major depressive disorder may display substantial

differences in prognostic and therapeutic terms (70 – 72).

If a rating scale is no more than a particular way of

recording clinical judgment (73), careful symptom discrimination by interviewing may allow the attribution of

differential emphasis on specific symptoms. In clinimetrics, major and minor symptoms may be discriminated,

unlike in psychometrics, where all items are weighed the

same (55). A recent example was provided by the use of

an item of the Clinical Interview for Depression (74),

reactivity to social environment, to characterize the clinical features (75) and response to treatment (76) of cyclothymic disorder.

The clinimetric perspective

The clinimetric perspective provides an intellectual home

for the reproduction and standardization of the clinical

intuitions (56). If associated with a broader cultural movement, it may address many of the difficulties that psychiatry is currently encountering. Pharmaceutical psychiatry is

leading to a marginal role of the specialty in the medical

system and to a perceived restriction of the psychiatrist ’ s

role to prescribing and signing forms, limiting opportunities to engage in the kind of integrated care that attracted

many physicians to the field (77). There is increasing

awareness of the limitations of current treatment strategies

that are unable to provide recovery in the majority of

patients (77). The case of major depression is particularly

illustrative (78), including the fact that there are no significant differences between treatments provided by psychiatrists compared with primary care physicians (79).

Beyond the concept of disease:

the emerging role of macro-analysis

In most instances of diagnostic reasoning in psychiatry,

the process ends with the identification of a disorder,

If we peruse the literature for clinical studies con-

cerned with samples homogeneous for treatment history,

we may fi

nd out that we do not even have adequate

information from observational studies or open therapeu-

tic trials (21). Borm & Donders (96) have suggested

that a series of small trials with at least 30% power is

preferable to a single large one. These small trials may

actually provide important clinical information that is

immediately helpful to the clinician encountering that

specific patient. This strategy would actually constitute a

paradigm shift in psychiatry. Conflicting results among

randomized controlled trials can represent a spectrum of

outcomes, based on different patient groups, more than

bias or random variability (97).

Regaining intellectual independence

In recent years, the Leitkultur of evidence-based medicine,

because of the influence of special interest groups on

medical societies and their media (journals, newsletters,

meetings etc.), has become the preferred tool of pharmaceutical propaganda.

Its reductionistic approach centered on the average

patient hiding the wide fluctuations that may occur in

treatment response.

The variability in response

Horwitz et al. (98) developed a method of clinical inquiry

within randomized controlled trials that can enhance

the applicability of results to clinical decision making.

Re-analyzing the Beta-Blocker Heart Attack Trial, they

found that propranolol reduced the risk of dying for the

“ average ” patient who survived an acute myocardial

infarction, whereas it was harmful in a subgroup of

patients characterized by specific cotherapy histories. If

we accept the possibility that a treatment that is helpful

on average may be ineffective on some and even harmful

on someone else, we may learn that a given therapy may

not be of value for a particular class or subgroup of

patients who are defined in terms of more detailed

(compared with the RCT eligibility criteria) specifications

of clinical conditions. This may stimulate further research

on alternative therapies that could potentially benefit

the class of patients defined by the subgroup for whom

otherwise effective therapy is providing no benefit or

may even be causing harm (98). Many examples may be

provided in the field of psychopharmacology (2), such

as with the use of atypical antipsychotic drugs (99), as

well as in psychotherapy research (100). The pharmaceutical industry obviously wants to avoid the phase of

disillusionment, which follows the report of toxic

unwanted effects, after an initial stage of enthusiasm for

the “ wonder drug ” , which is then prescribed excessively

and inappropriately (2). As a result, the pharmaceutical

industry is likely to censor, with the help of special interest groups, who act as editors, reviewers and consultants

sequential approaches may be necessary. The traditional

psychiatric paradigm still endorses the conviction that

psychotropic drugs work by acting on a disease process,

which the propaganda translates into “ curing ” psychiatric

disease. However, there is substantial evidence to call

such views in question (89).

New research on clinical judgment

In 1967, Alvan Feinstein (52) urged clinicians to develop

a “ basic science ” of their own — to study the clinical

phenomena directly, to specify the importance of different types of clinical data, to create appropriate systems

of taxonomy for classifying the information, and to

develop intellectual models and pragmatic methods that

would articulate the clinical process and use the results

for quantified analyses. Such line of research, which

affects clinical decision making (90), has been neglected

(56). The fact that clinicians browsing a journal issue

may no longer find any article relevant to their practice

is a direct consequence of such neglect.

Exclusive reliance on diagnostic criteria has impoverished the clinical process and does not reflect the complex thinking that underlies decisions in psychiatric practice (56). The use of transfer stations with repeated assessments instead of diagnostic endpoints, the building of global formulations of clinical integration, staging methods, an expansion and a better organization of clinical information, encompassing subclinical distress (30),illness behavior (91), lifestyle (92) and psychological well-being (93 – 95) may be an antidote to oversimplified models that derive from biological reductionism, neglect individual responses to treatment and clash with clinical

reality (56). A large amount of clinical research is derivative: methods are often applied in clinical studies simply because they have become available. If the clinical problem itself is poorly defined and obfuscated by marketing strategies, the focus of neurobiological research is set for random effort and misunderstanding.

Research designs and strategies

An intervention can be either evaluated by a single large

trial or by a series of smaller trials (96). The current

standard of therapeutic trial in psychiatry nowadays is

represented by the US large, multi-center, controlled,

randomized trial with very specific inclusion and exclu-

sion criteria, but little attention to the clinical history

of patients (42). Not surprisingly, however, the conclu-

sions that can be drawn by these trials are very limited

and offer trivial variations on tired themes. An increasing

number of researchers has no familiarity with the clinical

process and their research indeed reflects their naivet é .

In the meanwhile, pharmaceutical medicine is taking full

advantage of the clinical vacuum, providing directions

with massive doses of propaganda.

 This process of regaining intellectual independence not only involves researchers, but each clinician and society member. I recently refused to pay the American Psychiatric Association annual dues, because of the dramatic inadequacy of the society in handling the issues related to conflict of interest and clinical

challenges. Such stands have personal costs, but are in

line with the expression of intellectual freedom.


Often, in their clinical practice, psychiatrists use sophisticated forms of clinical judgment that are suitable for clinical challenges, but are not addressed by current research strategies. A renewed interest in the process of

clinical judgment (56) and in psychopathology as a science (8) may entail solution to the current impasse of

psychiatric research and practice. The notion of psychiatric disease is not in line with the changed spectrum of

health and the complex interplay of biological and psychosocial factors (56). Evidence-based medicine leads to

undertreatment, overtreatment or mistreatment, and is not

geared to the complexity of clinical situations. Alterna-

tive models that articulate the clinical process may pave

the way to a renewal of the appraisal of clinical judg-

ment in psychiatry.


— This paper is based on a lecture delivered at the Annual Finnish Psychiatric Association meeting in Helsinki, 2011.


Engel GL . Physician scientists and scientifi

c physicians . Am J


Med 1987 ; 82 : 107 – 11 .

Fava GA . The intellectual crisis of psychiatric research .


Psychother Psychosom 2006 ; 75 : 202 – 8 .

Feinstein AR . The intellectual crisis in clinical science . Persp


Biol Med 1987 ; 30 : 215 – 30 .

Insel T , Cuthbert B , Gavery M , Heinssen R , Pine DS , Quinn K ,


Sanislow C , Wang P . Research Domain Criteria (RDoC): Toward

a new classifi

cation framework for research on mental disorders .

Am J Psychiatry 2010 ; 167 : 748 – 51 .

Fava GA . The clinical factor . Psychother Psychosom 2011 ; 80 : 1 – 3 .


Balon R . Clinical factor 2010 . Psychother psychosom


2011 ; 80 : 195 – 8 .

Risch N , Herrell R , Lehner T , Liang KY , Eaves L , Hoh J ,


Griem A , Kovacs M , Ott J , Merikangas KR . Interaction between

the serotonin transporter gene (5-HTTLPR), stressful life events,

and risk of depression: A meta-analysis . JAMA 2009 ; 301 :

2462 – 71 .

Lipowski ZJ . Psychopathology as a science: Its scope and tasks .


Comp Psychiatry 1966 ; 7 : 175 – 82 .

Faust D , Nurcombe B . Improving the accuracy of clinical


judgment . Psychiatry 1989 ; 52 : 197 – 208 .

to medical journals and non-profi

t research organizations,

any data suggesting that a specifi

c drug may also lead

to a worse outcome. Of course, subgroup analyses can

entail serious methodological problems, such as multi-

plicity concerns (101) and advanced specifi

cation of sub-

sets (102). Yet, these analyses are in line with the object

of clinical inquiry (103).

The specifi city of clinical science

Engel identifi

ed the key characteristic of clinical science

in its explicit attention to humanness, where observation

(outer-viewing), introspection (inner-viewing) and dia-

logue (inter-viewing) are the basic methodological triad

for clinical assessment and for making patient data scien-


c (104). The exclusion of this interaction by medical

science ’ s continuing allegiance to a 17th-century scien-


c world view makes this approach unscientifi

c (105).

Unlike 20th-century physics, “ ... the human realm either

has been excluded from accessibility to scientifi

c inquiry

or the scientifi

c approach to human phenomena has been

required to conform to the reductionistic, mechanistic,

dualistic predicates of the biomedical paradigm ” (105,

p. 14). Not surprisingly, the evidence-based medicine

educated clinician is often not geared to tackle complex

clinical problems conceptually.

A reappraisal of evidence-based medicine

Evidence-based medicine certainly gave an important

historical contribution to the scientifi

c development of

medical literature in the past two decades. The time has

come, however, to become aware of its considerable lim-

itations, overall reductionism, insuffi

cient consideration

of problems related to fi

nancial confl

icts of interest, dis-

regard of the patient – physician relationship (including

patient ’ s preferences) and the need for integration with

clinical judgment. Not only do guidelines need to be

individualized (106), but alternative ways of assessing

evidence should be explored. For instance, in discussing

treatment options in depression, the choice of the main

evidence-based treatment ingredients in depression (phar-

macotherapy and psychotherapy) can be placed in the

context of clinical judgment (107), outlining the advan-

tages and disadvantages that each treatment selection


The role of scientifi

c societies

The scientifi

c societies that underlie the guideline-making

process do not provide an adequate background for intel-

lectual independence (10). Furthermore, society meetings

are still held on an annual basis, causing major ecologi-

cal wastes due to thousands of people travelling for

reaching the sites, and refl

ect a 20th-century communica-

tion paradigm, where meetings were of the main source

of scientifi

c novelties compared with printed journals. At

a time of information available to scientifi

c community

Fontanarosa PB , Flanagin A , de Angelis CD . Reporting confl



of interest, fi

nancial aspects of research, and role of the sponsors in

funded studies . JAMA 2005 ; 294 : 110 – 11 .

Rothman DJ , McDonald WJ , Berkowitz CD , Chimonas SC ,


DeAngelis CD , Hale RW , Nissen SE , Osborn JE , Scully JH Jr ,

Thomson GE , Wofsy D . Professional medical associations and

their relationships with industry. A proposal for controlling confl


of interest . JAMA 2009 ; 301 : 1367 – 72 .

Feinstein AR , Horwitz RI . Problems in the “ evidence ” of “ evidence-


based medicine ” . Am J Med 1997 ; 103 : 529 – 35 .

Glassman PA , Hunter Hayes J , Nakamura T . Pharmacological


advertising revenue and physicians organizations: How much is

too much? West J Med 1999 ; 171 : 234 – 5 .

Cosgrove L , Krimsky S , Vijayaraghavan M , Schneider L .


Financial ties between DSM-IV panel members and the

pharmaceutical industry . Psychother Psychosom 2006 ; 75 : 154 – 60 .

Cosgrove L , Bursztajn HJ , Krimsky S , Anaya M , Walker J .



icts of interest and disclosure in the American Psychiatric

Association ’ s Clinical Practice Guidelines . Psychother Psychosom .

2009 ; 78 : 228 – 32 .

Healy D . Irrational healers? Psychother Psychosom 2008 ; 77 :


198 – 200 .

Tomba E . Nowhere patients . Psychother Psychosom 2012 ; 81 : 69 – 72 .


Arfken CL , Balon R . Declining participation in research studies .


Psychother Psychosom 2011 ; 80 : 325 – 8 .

Lewontin RC . Biology as ideology . New York: Harper and Collins ;


1991 .

Lipowski ZJ . Psychiatry: Mindless or brainless, both or neither?


Can J Psychiatry 1989 ; 34 : 249 – 54 .

Kendler KS . Toward a philosophical structure for psychiatry .


Am J Psychiatry 2005 ; 162 : 433 – 40 .

Van Praag HM . Over the mainstream: Diagnostic requirements for


biological psychiatry research . Psychiatry Res 1997 ; 72 : 201 – 12 .

Belmaker RH . The future of depression psychopharmacology .


CNS Spectr 2008 ; 13 : 682 – 7 .

Byrne SE , Rotschild AJ . Loss of antidepressant effi

cacy during


maintenance therapy . J Clin Psychiatry 1998 ; 59 : 279 – 88 .

Paykel ES , Tanner J . Life events, depressive relapse and mainte-


nance treatment . Psychol Med 1976 ; 6 : 481 – 5 .

Karlsson H , Hirvonen J , Kajander J , Markkula J , Rasi-Hakala H ,


Salminen JK , Nagren K , Aalto S , Hietala J . Psychotherapy increases

brain serotonin 5-HT1A receptors in patients with major depressive

disorder . Psychol Med 2010 ; 40 : 523 – 8 .

Feinstein AR . Clinical Judgment . Baltimore, MD: Williams &


Wilkins ; 1967 .

Feinstein AR . The Jones criteria and the challenge of clinimetrics .


Circulation 1982 ; 66 : 1 – 5 .

Feinstein AR . Clinimetrics . New Haven, CT: Yale University Press ;


1987 .

Fava GA , Tomba E , Sonino N . Clinimetrics: The science of clinical


measurements . Int J Clin Practice 2012 ; 66 : 11 – 15 .

Fava GA , Rafanelli C , Tomba E . The clinical process in psychiatry:


A clinimetric approach . J Clin Psychiatry 2012 ; 73 : 177 – 184 .

Tomba E , Fava GA . The emerging role of clinimetrics in


psychological assessment . In Lange MA , editor , Leading-edge

psychological tests and testing research . New York: Nova Science

Publishing ; 2007 . p. 129 – 43 .

Fava GA , Kellner R . Staging: A neglected dimension in psychiatric



cation . Acta Psychiatr Scand 1993 ; 87 : 225 – 30 .

McGorry P , Hickie IB , Yung AR , Pantelis C , Jackson HJ . Clinical


staging of psychiatric disorders . Aus N Zeal J Psychiatry

2006 ; 40 : 612 – 22 .

Bilsbury CD , Richman A . A staging approach to measuring


patient-centred subjective outcomes . Acta Psychiatr Scand 2002 ;

106 Suppl 414) : 5 – 40 .

Andresen R , Caputi P , Oades L . Stages of recovery instrument .


Aust N Zeal J Psychiatry 2006 ; 40 : 972 – 80 .

Fava GA , Grandi S , Zielezny M , Canestrari R , Morphy MA .


Cognitive behavioral treatment of residual symptoms in primary

major depressive disorder . Am J Psychiatry 1994 ; 151 : 1295 – 99 .

63. Fava GA , Rafanelli C , Grandi S , Conti S , Belluardo P . Prevention of

recurrent depression with cognitive behavioral therapy . Arch Gen

Psychiatry 1998 ; 55 : 816 – 20 .

Fava GA . Unmasking special interest groups: The key to addressing



ict of interest in medicine . Psychother Psychosom

2010 ; 79 : 203 – 7 .

Maj M . Are psychiatrists an endangered species? World Psychiatry


2010 ; 9 : 1 – 2 .

Katschnig H . Are psychiatrists an endangered species? Observations


on internal and external challenges to the profession . World

Psychiatry 2010 ; 9 : 21 – 8 .

Chomsky N . Media control. The spectacular achievements of


propaganda. New York: Seven Stories ; 1997 .

Feinstein AR . Meta-analysis: Statistical alchemy for the 21st


century . J Clin Epidemiol 1995 ; 48 : 71 – 9 .

Tricco AC , Tetzlaff J , Moher D . The art and science of knowledge


synthesis . J Clin Epidemiol 2011 ; 64 : 11 – 20 .

Fava GA . Meta-analyses and confl

ict of interest . CNS Dugs


2012 ; 26 : 93 – 6 .

Baldwin D , Woods R , Lawson R , Taylor D . Effi

cacy of drug


treatments for generalised anxiety disorder: Systematic review

and meta-analysis . BMJ 2011 ; 342 : d1199 .

Furukawa TA . Drug treatment for generalized anxiety disorder .


BMJ 2011 ; 342 : d1216 .

Fava GA . Statistical alchemy for drug treatment of generalized


anxiety disorder: A commentary on the meta-analysis by Baldwin

et al. (BMJ 2011;342:d1199) . Psychother Psychosom 2011 ; 80 :

261 – 3 .

Berney P , Halperin D , Tango R , Daeniker-Dayer I , Schulz P . A


major change of prescribing pattern in absence of adequate

evidence: Benzodiazepines versus newer antidepressants in anxiety

disorders . Psychopharmacol Bull 2008 ; 41 : 39 – 47 .

F a v a G A , O f fi

dani E .

The mechanisms of

tolerance in



action . Progr Neuro-Psychopharmacol Biol Psychiatry 2011 ; 35 :

1593 – 602 .

Fava GA , Bernardi M , Tomba E , Rafanelli C . Effects of gradual


discontinuation of selective serotonin reuptake inhibitors in panic

disorder with agoraphobia . Int J Neuropsychopharmacol 2007 ;

10 : 835 – 8 .

Pereira TV , Ioannidis JPA . Statistically signifi

cant meta-analyses


of clinical trials have modest credibility and infl

ated effects . J Clin

Epidemiol 2011 ; 64 : 1060 – 9 .

Al Khalaf MH , Thalib L , Doi SAR . Combining heterogeneous


studies using the random-effects model is a mistake and leads to

inconclusive meta-analyses . J Clin Epidemiol 2011 ; 64 :

119 – 23 .

Moher D , Liberati A , Tetzlaff J , Altman DG , the Prisma


Group . Preferred reporting items for systematic reviews and

meta-analyses: The PRISMA statement . J Clin Epidemiol 2009 ; 62 :

1006 – 12 .

Fava GA , Kellner R . Prodromal symptoms in affective disorders .


Am J Psychiatry 1991 ; 148 : 823 – 30 .

Molnar G , Feeney G , Fava GA . Duration and symptoms of bipolar


prodromes . Am J Psychiatry 1988 ; 145 : 1576 – 8 .

Perry A , Tarrier N , Morriss R , McCarthy E , Limb K . Randomized


controlled trial of effi

cacy of teaching patients with bipolar disorder

to identify early symptoms of relapse and obtain treatment . BMJ

1999 ; 318 : 149 – 53 .

Tomba E , Fava GA . The sequential combination of pharmacother-


apy and psychotherapy in mood disorders . J Contemp Psychother-

apy 2009 ; 39 : 101 – 9 .

Fava GA . Subclinical symptoms in mood disorders:


Pathophysiological and therapeutic implications . Psychol Med

1999 ; 29 : 47 – 61 .

Jackson A , Cavanagh J , Scott J . A systematic review of manic and


depressive prodromes . J Affect Disorder 2003 ; 74 : 209 – 17 .

Skjelstad DV , Malt UF , Holte A . Symptoms and signs of the initial


prodrome of bipolar disorder . A systematic review. J Affect Disord

2010 ; 126 : 1 – 13 .

Howes OD , Lim S , Theologos G , Yung AR , Goodwin GM ,


McGuire P. A comprehensive review and model of putative

prodromal features of bipolar affective disorder . Psychol Med

2011 ; 41 : 1567 – 77 .

Laupacis A , Straus S . Systematic reviews. Time to address clinical


and policy relevance as well as methodological rigor . Ann Intern

Med 2007 ; 147 : 273 – 5 .

Nord J Psychiatry Downloaded from informahealthcare.com by on 07/22/13

For personal use only.

No comments:

Post a Comment