further thoughts on the mistake…

Posted on Monday 28 May 2012

Back in December, I had a shot at describing Melancholia [melancholia…]. But there are certainly better versions. Dr. Bernard Carroll’s clinical description in verse is unlikely to ever be surpassed [Bringing back melancholiafull text on-line]. And there are vivid internal descriptions by sufferers [Darkness Visible: A Memoir of Madness by William Styron and An Unquiet Mind: A Memoir of Moods and Madness by Kay Jamison come to mind]. It’s the kind of Illness experienced by people with Manic Depressive Illness in its varieties, or as a standalone illness that often recurs. It’s hard to describe without using quantitative terms like severe or profound but it’s not the severity that defines it. This next commentary is from 2010 in a plea by some of our best and brightest to include it as a distinct entity in the DSM-5 – a plea unheeded:
Issues for DSM-5: Whither Melancholia?
The Case for Its Classification as a Distinct Mood Disorder
American Journal of Psychiatry. 2010 167:7.

Melancholia, a syndrome with a long history and distinctly specific psychopathological features, is inadequately differentiated from major depression by the DSM-IV specifier. It is neglected in clinical assessment [e.g., in STAR*D] and treatment selection [e.g., in the Texas Medication Algorithm Project]. Nevertheless, it possesses a distinctive biological homogeneity in clinical experience and laboratory test markers, and it is differentially responsive to specific treatment interventions. It therefore deserves recognition as a separate identifiable mood disorder. Melancholia has been variously described as “endogenous,” “endogenomorphic,” “autonomous,” “type A,” “psychotic,” and “typical” depression. In contrast to the current DSM criteria for the melancholia specifier [features of which are often shared with major depression], it has characteristic clinical features.

Clinical Features

  1. Disturbances in affect disproportionate to stressors, marked by unremitting apprehension and morbid statements, blunted emotional response, nonreactive mood, and pervasive anhedonia—with such features continuing autonomously despite any improved circumstances. The risks for recurrence and for suicide are high.
  2. Psychomotor disturbance expressed as retardation [i.e., slowed thought, movement, and speech, anergia] or as spontaneous agitation [i.e., motor restlessness and stereotypic movements and speech].
  3. Cognitive impairment with reduced concentration and working memory.
  4. Vegetative dysfunction manifested as interrupted sleep, loss of appetite and weight, reduced libido, and diurnal variation—with mood and energy generally worse in the morning.
  5. Although psychosis is not necessarily a feature, it is often present. Nihilistic convictions of hopelessness, guilt, sin, ruin, or disease are common psychotic themes.
Biological Changes
Several biological changes occur more frequently in melancholia than in other forms of depressive illness. Three indicative markers are known.

  1. Hypercortisolemia, reflected in the dexamethasone suppression test (DST). It is common in melancholia and relatively uncommon in nonmelancholic mood disorders.
  2. Psychomotor disturbance measurable by the CORE scale, with CORE scores demonstrating a linear relationship with DST nonsuppression rates.
  3. Characteristic disturbances in sleep architecture, with reduced REM latency, increased REM time, and reduced deep sleep.
Melancholic patients respond better to broad-action tricyclic antidepressants than to narrow-action antidepressants (e.g., serotonin uptake inhibitors). They respond well to ECT. In comparison to those with nonmelancholic mood disorders, melancholic patients rarely respond to placebos, psychotherapies, or social interventions.

Melancholia is a lifetime diagnosis, typically with recurrent episodes. Within the present classification it is frequently seen in severely ill patients with major depression and with bipolar disorder. Melancholia’s features cluster with greater consistency than the broad heterogeneity of the disorders and conditions included in major depression and bipolar disorder. The melancholia diagnosis has superior predictive validity for prognosis and treatment, and it represents a more homogeneous category for research study. We therefore advocate that melancholia be positioned as a distinct, identifiable and specifically treatable affective syndrome in the DSM-5 classification.

Besides the clinical description above, there’s a felt solemnity, like being in a Medieval Stone church on an overcast dreary day. Talking or asking questions feels pointless, hopeless, almost wrong. I’ve always thought of it as a noun [the patient is depression] as opposed to an adjective [the patient is depressed]. The described emotion or the one empathically felt isn’t on a continuum with sadness. It’s something else ["Unlike grief, dark motif" – Carroll]. But whatever way you choose to describe it, it’s different from other more common depressions that can be severe, even fatal, but they lack the unique qualities of Melancholia. They are described more like profound sadness. The empathic feeling is sadness, sometimes rage, but it’s not the alien feeling of Melancholia. They’re just different things and the difference is more apparent in person than it is when you try to read or write about it. Just thinking about it to write this, it seem impossible to imagine that these things would be categorized together in any diagnostic system, yet they were [paradoxically, by a man who is an author on the plea above – Robert Spitzer].

In the earlier DSM Manuals, the distinction wasn’t so necessary [still hypothesizing…]. It was almost built into the system – the Major Affective Syndromes being primarily the Melancholic Depressions and the Psychoneuroses being the commoner forms of Depressive Illness. Here are the Research Diagnostic Criteria [RDC] again as a reminder:

The subcategories under Major Depressive Disorder did not come from actual research. Like the Feighner Criteria, they came from the literature, from the collective attempts of psychiatrists who had come before to make inroads into our understanding of depression using descriptive or historical criteria. Notice that Melancholia is not on the list. For many, at that time, Melancholia was a term from history. The Endogenous versus Exogenous distinction was widely used – an etiologic classification that was faltering primarily because of examples where a significant number of clinically Endogenous cases seemed to be precipitated by life circumstances. That aside, the conditions under Major Depressive Disorder were predominantly terms people had devised to parse the Melancholic Depressions [exception Situational, maybe Secondary].

We use the term "major depressive disorder" as it seems general enough to encompass the many further subdivisions that are the basis of much current research. This category includes some cases that would be categorized as neurotic depression, and virtually all that would be classified as involutional depression, psychotic depression, and manic depressive illness, depressed type.

Notice the use of the world "some." I presume that those were the severe cases of neurotic depression. But the point here is that Spitzer and his colleagues were primarily talking about what we are calling here Melancholia. The counterpoint, Minor Depressive Disorder, was described:
Depressive Disorders Not Meeting the Full Criteria for Major Depressive Disorder: There is even more controversy as to the best way of classifying subjects who are bothered from time to time more than most people by depressive mood and associated symptoms but who do not meet the full criteria for major depressive disorder.
I’m afraid I’m going to have to give the RDC Group a grade of F on their handling of this diagnosis. I know that at the time, they were declaring war on psychoanalytic formulations, but that doesn’t justify the diminutive description given here. There’s nothing that separates it from their Major Depressive Disorder except severity and even the name, Minor Depressive Disorder, is discounting. There are a lot of people who die every year from suicide who are in this category, I daresay more than from Melancholia, to evoke a popular Public Health argument. And a term like Minor Depressive Disorder has no place on a Death Certificate. There’s nothing "Minor" about death. In Edward Shorter’s classic history, Before Prozac: The Troubled History of Mood Disorders in Psychiatry, [complete with interviews of the principals], he documents that there was debate aplenty on this point as the DSM-III was being constructed with arm twisting, name changing, pushing and shoving [pp. 158]. Needless to say, the term didn’t make it into the DSM-III. But for our purposes here, it implied a lesser depression than Melancholia, no matter the name, and that sentiment of lesser contributed to the big mistake contained in the Research Diagnostic Criteria, the one that haunts us still [a mistake…]. One can speculate about why that happened ad nauseum. Neurotic Depression was a broad term, both heterogeneous in proposed etiology and widely variant in severity. Some biological psychiatrists thought it wasn’t the business of psychiatry to even involve itself with this group. It wasn’t real depression. It wasn’t medical. And at that time, almost all of them would have rightly excluded such patients from their biological research cohorts – too fuzzy and probably resulting from non-biological causes.

Another fact of life that must have affected the construction of these criteria  had to do with the groups studied in the process of building them. "Study A used an early draft of the RDC and involved 68 newly admitted inpatients at the New York State Psychiatric Institute"; "Study B … subjects were newly admitted inpatients who met screening criteria for a depressive or manic syndrome"; "The test-retest reliability study was conducted at the same four facilities as study B … involving a different group of newly admitted inpatients". It was a different time in history and psychiatric hospitalization was much more available. Melancholic Depression frequently lead to admission for evaluation and treatment. Only severe cases of Neurotic Depression were admitted, primarily based on suicidality. Melancholic Depression was, in those days, mostly an inpatient disease and Neurotic Depression was primarily an outpatient condition. That must have heavily skewed the results used in arriving at the criteria.

It’s not my intent to go off on a diatribe about the plight of the neurotically depressed, though it might make a very valid and useful point. My goal is to say two things. First, replacing the dichotomy of Major Affective Disorder and Depressive Neurosis with Major Depressive Disorder and Minor Depressive Disorder removed a categorical distinction and replaced it with a severity scale. Second, while there may well have been an opinion among some biological psychiatrists that Neurotic Depression was not a proper arena for psychiatrists, expressing that opinion in the diagnostic system was actually a mistake for them that had a paradoxical outcome – dramatically impeding the biological research in depression. Whether intentional or inadvertent, the Research Diagnostic Criteria ultimately inserted a legitimacy scale into our diagnostic system with disastrous consequences. Stay tuned…
    May 29, 2012 | 11:30 AM

    Well the first name I saw in the article that gives reason for any recommendation of ECT use for treatment is MAX FINK, of course he’d recommend ECT that’s his life work.

    May 29, 2012 | 1:07 PM

    Well in my experience ECT is the most effective treatment for melancholic depression. I have seen some truly remarkable responses to very severe and life threatening depression.

    May 29, 2012 | 2:51 PM

    In case you haven’t read this yet: Grassley goes after NIH over Nemeroff grant – http://freepdfhosting.com/ee8f43562b.pdf

    May 29, 2012 | 3:01 PM

    Say, Tom, how long did that remarkable response last? As long as the amnesia?

    May 29, 2012 | 3:08 PM

    “I have seen some truly remarkable responses to very severe and life threatening depression.”

    that’s a nice sounding subjective statement…but where is the concrete evidence…what’s the electricity actually doing to the brain tissue..I’m quite sure a memory wipe would do wonders for someone with depression…but is that a treatment or a stop gap measure with dangerous and long term negative consequences?

    This goes to the root of psychiatry’s main problem…they theorize, make hypothetical promises, put these sort of treatments into actual practice, and then put off the real understanding and science for somewhere decades down the road; which may I add, consequently never seems to pan out…..then they just repackage the same old junk science ideas and go through this fantasy process all over again..evidence based medicine be damned…

    Heck, the ECT devices are not even regulated; or do they go through proper tested and clinical trials before going into use..just more darts being thrown in the dark by misguided medical fortune tellers…but by gosh it works for some unknown reason…trust me on it….I can only say in response NO THANK YOU…you have used up all your “trust me” cards…

    May 29, 2012 | 3:09 PM

    Stan, You just made my day! Viva Grassley…

    May 29, 2012 | 5:37 PM

    Amen, Mickey! Thank you, Stan! Thank you, thank you! Will be interested in the response requested by June 12. Wonder where Insel is in all this. I have a friend who is a journalist; when he took writing classes at Queens he was in the “creative non-fiction” section (as opposed to fiction or poetry). Each section came up with their own t-shirts. His? “You can’t make this s…. up!”

    May 29, 2012 | 6:49 PM

    Just a voice from the other end of the spectrum… that of the “patient.” No, I have not had ECT or been hospitalized. I’m just starting out on the “meds” treadmill, hoping to make a dent in my depression and other issues. That being said, after reading this, absent some clearcut PROOF that ECT provides lasting relief, would I let anyone DO that to me? Uh… No.

    May 29, 2012 | 7:22 PM

    Go Senator Grassley! Nemeroff– or something stinks and it glows in the dark! not hard to find that pharma paid KOL when it comes to corruption he’s right there! Watch out , he’s on the board of directors of a urology pharma company too; besides the aerosol spray Ambien! $$$$ is all that guy is about, and he needs to be removed permanently from ALL government funded trials and grants!

    Joel Hassman, MD
    May 29, 2012 | 9:06 PM

    People die from being given penicillin. Let’s outlaw that drug pronto!

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