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MelancholiaReview - Melancholia
The Diagnosis, Pathophysiology and Treatment of Depressive Illness
by Michael A Taylor and Max Fink
Cambridge University Press, 2006
Review by Roy Sugarman, Ph.D.
Jan 1st 2008 (Volume 12, Issue 1)

To let you know from the outset why this book uses a term that is seldom bandied about in professional tomes, a quote from the authors is in order:

Early International Classification of Diseases (ICD) editions and DSM-I and DSM-II classifications identified melancholia, but these classification systems were not helpful in prescribing newly introduced treatments ... that were found to be effective in schizophrenia and then in manic-depressive illness.  The efficacy of psychotropic drugs was also weakly correlated with heterogeneous DSM categories, discouraging the search for treatment response as a feature for classification.  The DSM-III and subsequent classification introduced as operationally defined and more "scientific", produced no better results. To achieve the approval of the largest segments of the diverse membership[s of professional organizations, the DSM definition of mood disorder became overly broad and criteria for the diagnosis of major depression overly liberal. The "worried well" with characterological depressive moods were conflated with melancholia into the category of "major depression".  The neuroendocrine, neurophysiologic, and psychopathological delineators of melancholia were confounded, and discarded as diagnostic and prognostic clinical laboratory aids ... .  In response to weakened criteria and confusing classification, we reintroduce melancholia as the classic depressive illness with definable diagnostic criteria and effective treatment algorithms (pages xii-xiii).

These authors are no alone in criticizing the criteria and definitions used to describe the clinical diagnosis and clinical pathways for mental illness.  No less a luminary as Steve Hyman, the past head of the NIMH recently (Nature Reviews Neuroscience, September 2007) asked whether neuroscience was ready to inform on the DSM-V. He called for a less categorical, more continuous approach to the nosological framing of mental illness. This was based on findings for instance that although a family member may receive a categorical diagnosis such as Schizophrenia, other members of the family can be found to have some features of the illness even if they are not diagnosed in terms of the categories of the DSM or ICD.

Other authors, such as Ronald Miller have criticized the current evidence based approach to both training and practice in psychiatry as failing to effectively allow for clinicians to engage with human suffering, and others such as Spaulding, Sullivan and Poland have described the mechanics of a community approach to mental illness based on the wide and polymorphous spread of symptoms within a single diagnostic entity.

The conceptual history and definitions provided by these authors are designed to support their argument that melancholia is not only a defined clinical entity, but that doing so also provides for a clear set of clinical tests of the psychophysiology of the sufferer that identify the condition reliably.  They offer the examples of seemingly unreliable tests, which, when applied only to those with a clearly defined illness such as this, produce valid and reliable discrimination from other illnesses or conditions.

Melancholia is a recurrent, debilitating, pervasive brain disorder that alters mood, motor functions, thinking, cognition, perception and many basic physiologic processes (page 15).  In this way, pathological mood can be described, in pervasive and unremitting apprehension terms, psychomotor disturbance is second characteristic, vegetative functions are disrupted, and psychosis is recognized when the mood is severe in about 30% of patients and is seen as an integral part of melancholia.

These authors are not alone in defining melancholic depression either.  Prof Gordon Parker of the Australian "Beyond Blue" organization likewise regards motor disturbances as a hallmark of melancholia ( see as well as psychotic melancholia.

Such discussions are astounding in the environment an advanced science such as psychiatry, and are somewhat disturbing evidence to be added to a plethora of works that psychiatric nosological categories are insufficient ecologically to sustain efficient practice.  Elements in the FDA report by personal communication that even though drug companies submit multiple compounds to the FDA each year, about 50% have insufficient data to support their approval and in those that are safe, most simply don't better placebo by more than 10%.  This is more likely to represent the filtering effect of using the DSM-IV categories to establish the drug cohorts rather than the drugs: if the target is ill defined, how does one establish which therapeutic arrows are likely to strike home?

Here, the authors then take their argument to several related conditions, such as bipolar and post partum disturbances, and demonstrates the logic of their targeted approach.

They point out that the boundaries have been blurred between melancholia and other heterogeneous or "mixed bag" conditions, such as dysthymia or premenstrual syndromes.  They conclude that melancholia, from the literature and experience of others, is a distinct syndrome, a specific depressive disorder, and offers a specific paradigm shift in thinking about mood disorder.  This shift allows for laboratory testing which lends credence to the idea that this is a 'real' rather than tailored entity. The diagnosis leads to tests for it being specific to the entity, rather than trying to find reliable tests for DSM entities, which so far have proved fruitless.  HPA tests and those of electrophysiology are put forward for consideration.

Apart from laboratory testing the authors needed to describe the exact clinical approach to examining for mood disorders of this type. This will include examining for vegetative signs and psychotic features, suicidal thoughts, cognitive falloff, personality disorder and so on.  Various inventories are also evaluated, with such stalwarts as the Beck Depression Inventory regarded as not being useful for assessing melancholia or in assessing the severity of depressive illness in hospital settings, although it is held to be useful in outpatient settings.  The differential diagnosis is also offered, with criteria against non melancholic depression, atypical depression, seasonal affective disorder, dysthymia, adjustment disorder and premenstrual disorder. The concept of the condition in children and adolescents is discussed, with an indication that incidence of comorbidities may be higher.  Also discussed here is autism, the elderly, patients with a psychotic disorder, OCD, drug-related conditions, and other typical DSM categories such as general medical conditions.  Suicide is taken seriously in melancholia, and so many aspects of this are discussed, with treatment often involving locked ward stays and ECT, as well as medication.

An extensive review of the risks for suicidality on modern SSRI's concludes that the interactions are complex and indirect.  A major worry has been the effect on adolescents; these authors conclude that if there is an increased risk of suicidality, it will be in the first week or so, owing to weak antidepressant and mild activating qualities of the drugs.  As noted, these authors make frequent reference to ECT in melancholia, and devote an entire chapter to this treatment.  They deconstruct its value in each of multiple conditions, commenting that the merits of ECT in melancholia are undisputed.  They do note the principal restrictions on its use are its "stigma and restrictions in its use, the special requirements for consent, and other non-clinical aspects".  Prof Gordon Parker agrees, in his writings on the subject, and also notes there may be value in transcranial magnetic stimulation as well.  These authors are more skeptical, and suggest the need for more studies.  Nevertheless, another chapter follows on precisely how to achieve effective ECT, as these authors feel this is a neglected field in treatment efficacy studies.

A long review is necessary into the pharmacotherapy of the illness, as if you change the 'target' as I mentioned above, you would need to review the literature on therapeutic arrows.  Here, the evidence is supported, as it is by Prof Gordon Parker, for the tricyclic agents rather than the SSRI's which are described as only weakly antimelancholic, overly energizing, so that they increase agitation and anxiety, and they degrade sleep.  Nortriptyline and desipramine are described as having only modest side effects, and are regarded as more effective in melancholia.

Having reviewed the medication effects in the literature, the authors turn to guiding the treatment via pharmacotherapy, including advice on augmentation in both melancholia and related conditions at different levels of severity.

An entire chapter is then devoted to complicating circumstances such as pregnancy, breastfeeding, childhood, adolescence, including the use of tricyclics and MAOI's in the young and the elderly.  Other medical conditions are also well examined, continuing the philosophy of these authors that the condition is as much as physical as a mental condition.

As noted briefly above, other putative treatments are discussed, with the reservations generally of the need for further elaboration.

Another chapter, this time more extensive, follows on the pathophysiology as it is the author's contention that the current dearth of laboratory findings in depressive disorders can be addressed, and are likely to emerge from studying the neuroendocrine system.  As throughout the book, the references are extensive.

Predictably, the "Future Directions" chapter begins with a discussion of the need to change the DSM classification of depression, melancholia, and standards for pharmacotherapy research, reducing noise in publications, reducing the influence of the industry, changing treatment guidelines, improving the education of medical practitioners, studying ECT and other therapies, and so on.  Hundreds of pages of references and Index complete the book.

I doubt anyone has ever written as comprehensive a book on any aspect of mood disorder, and although not much is new, the authors make a compelling argument which draws on a more integrative neuroscience than is usual in these texts.  Theirs is a particularly biological view, with no real room for psychotherapy in their formulation, and neither are psychologists anyway.  Gordon Parker feels similarly that it is not a first line treatment for melancholic or psychotic depression, but rather could be used for non-melancholic forms.

Overall an outstanding work, thorough and precise. It is written at several levels, and can be read by anyone, no matter what level of training or professional expertise.

© 2007 Roy Sugarman

Roy Sugarman, Ph.D., Director of Clinical and Neuropsychological Services, Brain Resource Company, Ultimo, Australia

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