depression, Depression, and Alchemy…

Posted on Thursday 28 April 2011


One would think that after thirty years of practicing as a Psychiatrist, it should be easy to read through this list of diagnostic criteria for Major Depressive Disorder and have something to say about it. But honestly, it leaves me as blank as it did the first time I read it back when it was first introduced in 1980.


A. Five [or more] of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either depressed mood or loss of interest or pleasure.
  1. depressed mood most of the day, nearly every day, as indicated by either subjective report [e.g., feels sad or empty] or observation made by others [e.g., appears tearful]. Note: In children and adolescents, can be irritable mood.
  2. markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day [as indicated by either subjective account or observation made by others].
  3. significant weight loss when not dieting or weight gain [e.g., a change of more than 5% of body weight in a month], or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
  4. insomnia or hypersomnia nearly every day.
  5. psychomotor agitation or retardation nearly every day [observable by others, not merely subjective feelings of restlessness or being slowed down].
  6. fatigue or loss of energy nearly every day.
  7. feelings of worthlessness or excessive or inappropriate guilt [which may be delusional] nearly every day [not merely self-reproach or guilt about being sick].
  8. diminished ability to think or concentrate, or indecisiveness, nearly every day [either by subjective account or as observed by others].
  9. recurrent thoughts of death [not just fear of dying], recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.
B. The symptoms do not meet criteria for a Mixed Episode.
C. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
D. The symptoms are not due to the direct physiological effects of a substance [e.g., a drug of abuse, a medication] or a general medical condition [e.g., hypothyroidism].
E. The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

I’ve tried to write about this numerous times, but always end up scrapping what I’ve said as missing the mark. This list has all the right stuff – dysphoric mood, vegetative symptoms, loss of interest in life or living, difficulty thinking clearly. It pretty much covers what one sees in a depressed person.

In the early days when I worked with people who were hospitalized, I met people who were profoundly depressed – in fact it was the only thing they could talk about [if they could talk at all]. I thought of those people as having Depression, like a noun. I had no difficulty thinking of  them as having a Disease. Some had had previous episodes. Some had had episodes of Mania before. Some got it in late life. Other got it after having a child. For some, it just seemed to happen out of the blue. So I learned the names of its various flavors and gave the antidepressants of the day, did ECT on some of the non-responders like my predecessors [and was amazed at the results]. I thought of those patients as having Major Depression [whichever sub-version]. Like with every patient, I tried to find things in the person’s life that might be a factor, but came up with nothing that meant very much in this group. I was taught that’s what Major Depression was and that’s how I found it. It came in severe, more severe, and profound – but not mild.

And then I saw depression – all the time. I never thought of it as a disease. I guess I saw it as more a sign or a symptom. Back then, it got coded as Neurotic Depression which more a descriptive diagnosis than a diagnosis of disease. The patients had vegetative signs and all the other things on the list up there, but to a lesser degree. Some had miserable life situations or bad things happening to them. Some were character disordered people. Some had grief that wouldn’t let go. Some had what Freud said, retroflexed rage. Some were people who were helpless in the face of life’s challenges. And some were like the people in the last paragraph, but the symptoms weren’t so pervasive. I could probably fill paragraphs with situations if I thought back over the years. I thought of those patients medically too. They had the signs and symptoms of depression, and I looked for a cause. It usually wasn’t that hard to locate. It was, however, a challenge to figure out how to deal with it. The "feeling better" outcome sometimes passed by imperceptibly because the outcome got re-framed in the process. Some people were treated with medications, others weren’t – it depended on things too variable to matter much in this discussion. That’s the story of the life of an analyst or a psychotherapist. To many psychiatrists, that’s all mumbo jumbo and a waste of time and money. Different strokes for different folks is all I have to say about that. The point here is that I saw depression as a pointer, a signal, a part of being human – not as a disease to be removed. I still see it that way.

There’s something about the way I approached things that I think was out of the norm. I never suggested psychotherapy or analysis to any patient. I always saw that as a choice and that the outcome was a lot better if I left that choice to the patient. And if I saw someone who only wanted to get rid of their symptom, I was glad to either try medications or refer them if that seemed a better choice. I could be a medical psychiatrist at the drop of a hat. I’m an Internist and had plenty of practice. Most people who were referred to me came looking for psychotherapy after failing with other modalities, but not all. But I didn’t think that the patients who only wanted to feel better had a disease. I thought they just only wanted to feel better [or sometimes, were in situations that they didn’t want to examine]. Their choice in my book.

That’s an introduction  to why I feel blank when I read those criteria up there. Depression as a disease and depression as a symptom/signal/pointer/human thing/etc. are all fused together under one heading and I find it virtually unusable in evaluationg a person. "I’m depressed" is a starting point, not a destination. When I read that STAR*D had 4041 subjects, I’m awed. I know it’s not 4041 people with Depression – they don’t come along in those kind of numbers. So by those criteria up there, it has to include that extremely heterogeneous collage of the many roads that lead to dysphoria – known and unknown. If these studies were labeled as the effect of medication on a symptom it would be one thing, but that’s not the way they’re written. They often start like this:
    Depression will be the second leading contributor to the burden of disease by 2020. There is therefore an urgent need to identify objective indicators of risk for depression, and to understand their link to underlying biological mechanisms and treatment.

    Depression is one of the most prevalent and costly brain diseases. In the last major epidemiology study conducted in the United States1, major depression had an overall lifetime prevalence rate of 17.1% (21% in women and 13% in men), and comparable figures have been obtained worldwide. These findings represent an increase of approximately 6% in the 15 years since the previous study2…

    Affective disorders account for considerable psychiatric morbidity (pain and suffering), but also significant disability and consequent loss of productivity. Depression has been estimated to be the second leading cause of disability worldwide, surpassed only by ischemic heart disease. Moreover, depression is often associated with comorbid psychiatric disorders, most notably anxiety disorders (panic disorder, generalized anxiety disorder, social anxiety disorder, obsessive−compulsive disorder and post-traumatic stress disorder). The mean age of onset of depression has markedly decreased from the 40- to 50-year-old range noted several years ago to the 25- to 35-year range, and this phenomenon has been observed worldwide. Depression often goes undetected, especially in children, adolescents and the elderly. Mood disorders are associated with a significant risk for suicide, which remains one of the top ten causes of death in the United States and in many countries throughout the world. Depression is a major independent risk factor for the development of coronary artery disease and stroke, and possibly other major medical disorders.

"biological mechanisms", "brain diseases", "second leading cause of disability worldwide" – sounds like an appeal to stomp out Guinea Worm or AIDS. It’s as if we’ve made a transition from a syndrome of symptoms to a brain disease with biological mechanisms skipping some essential intervening steps [like science] – and, by the way, these are introductions to articles about empiric treatments as yet unconnected to a clear causative pathway except by speculative hypotheses [and the heterogeneity is gone with the wind]. I don’t think that I’m closed to the idea that there are "biological mechanisms" involved in Depression and maybe depression too. It’s that when I read things like this, I feel like I’m being tricked, sold a bill of goods, being played for someone who wouldn’t notice the fallible logic.

I even ordered a dogeared DSM-III from Amazon to see how Major Depressive Disorder started [because I couldn’t find the original criteria on the Internet]. MDD came into existence in 1980 with the DSM-III and has remained essentially unchanged through DSM-IIIR, DSM-IV, and the proposed DSM-V. Am I bothered about this because it leaves out what I did in my career? I don’t think so. There were plenty of people looking to sort out their lives. I think it bothers me because it doesn’t fit my experience and because I’m suspicious of the motives involved – it’s the old "chemical imbalance" story without the actual phrase being used. I was recently told that 7% of Americans take antidepressants. I just don’t believe that one out of every twenty Americans has a "brain disease."

Given the magnitude of scientific misadventure in the psychopharmacologic research that fills this and many other blogs; the criminal level of conflicts of interest in the psychopharmacologic literature; the fact that almost every major drug manufacturer has been fined for suppressing or distorting scientific information and fraudulent advertising; I find it impossible to believe that similar forces have been absent in the construction of the Diagnostic and Statistical Manual – and specifically in the rigid adherence to the diagnostic category I’ve been taking about in this post – Major Depressive Disorder. More than any other, it is the one most closely connected with the high profit pharmaceuticals.

While I think that depression represents a broadly heterogeneous group of people connected more by symptom than by cause, in the end, that’s just something I think based on what I’ve seen. I’m just one person who may be wearing a set of glasses so influenced by my own experience that I can’t see clearly. On the other hand, the unity of this group is supported only by a loose set of symptoms. They don’t respond uniformly to medications – by a mile. There are no markers that have stood the test of time – if anything the candidate markers have defined subgroups. Large studies like STAR*D haven’t yielded any unifying characteristics [except that they drop out of studies in droves]. Finally, there are big studies of MDD – STAR*D, CO-MED, iSPOT to mention a few – that are collecting a large mass of global information on patients with this diagnosis. But that information is not being designed toward, collected for, or analyzed for clues that might explain the heterogeneity of this diagnostic category. It’s being collected for the personalized medicine trade – aiming towards a future testing/screening business enterprise and a market in marker-specific treatments. It’s as if keeping this Diagnosis broad is more important than looking into what it represents. It’s probably worth more when it’s imprecise.

My own take on all of this is that the neuroscientists are justified in their excitement over all the technological advances and the new access to genetic information, but so long as it’s all being used to find new products for commercial enterprises, it will not answer any of the real questions that need answering. In the video of Brain Resource’s Mayflower Action Group Initiative, Madhukar Trivedi said that what was important was to find out how to pick the right drug for the right person, not to find out about pathophysiological mechanisms. My take is that he is speaking for a large segment of his generation of neuroscientists. They’re like the Alchemists of old. "The King wants gold so we’ve got to figure out how to make it out of lead first. Discovering Chemistry will have to wait." In fact, the analogy to Alchemy occurs to me frequently when I listen to a lot of these guys. They speak eloquently about things they don’t yet understand…
    Bernard Carroll
    April 29, 2011 | 12:02 AM

    Thanks for highlighting the WHO Global Burden of Disease pabulum, which warns that depression will be the second global cause of disability by 2020.Whenever I see a journal article lead off with this anodyne theme I know there’s trouble ahead. The theme has been internalized by all the professional writers who do the ghostwriting for all the too-busy KOLs – we know who they are. By now it’s just part of the branding language.

    May 3, 2011 | 1:21 PM

    Hello there,

    First off, thanks for sharing your insights with us. Having grown up with the “chemical imbalance” approach to depression as the status quo (I’m 23), I appreciate your longer-term perspective.

    A question: among the folks in the first group (those with Depression), what recovery pattens did you see? Did some folks with serious Depression ever come to resemble those with depression while ‘getting better’?

Sorry, the comment form is closed at this time.