Dismantling “Major Depression”

Almost forty years after the publication in 1980 of the epic third edition of the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association, it is starting to become apparent that psychiatry made a historic mistake in getting rid of its traditional three or four depressive illnesses and replacing them with a single towering artifact, “major depression.”

Just to review: the main depressive illnesses before 1980 were:

• Melancholic depression, responsive to tricyclic antidepressants and electroconvulsive therapy
• Non-melancholic depression, previously called “reactive depression,” “depressive constitution,” or “neurasthenia,” among other historic terms, responsive to lots of different agents
• Atypical depression, notable for overeating, oversleeping, and high reactivity to bad news, responsive to monoamine oxidase inhibitors (MAOIs) such as Parnate
• Mixed anxiety-depression, responsive to benzodiazepines. This last depression would probably be the most problematical to classify separately. Yet Valium-style agents do seem effective in this particular picture while benzos in general are not really considered “antidepressants” (although this term has been bent so badly out of shape that it has become meaningless).

Then DSM-3 rode in and said, “There’s only one depression! We’ll call it ‘major.’” (Dysthymia in DSM-3 was really just a pattern of chronicity, not a separate illness.) Therewith, all the previous depressions were toast, and today nobody has ever heard of them. Melancholia, what’s that?

But a disaster of this magnitude could not go long unnoticed. And since 1980 the field has been trying to dismantle major depression, timidly at first, and now with increasing resoluteness. There have been a lot of research studies showing that different kinds of depressive illness really do exist and that maintaining the fiction of a single mood disorder is very convenient for the pharmaceutical industry, which gets to market “antidepressants” as a single highly profitable drug class – but harmful to patient care because, yeah, there are different treatments out there depending on what kind of depression you have.

The most recent pickaxe blow against this façade of major depression comes from Leuven University in Belgium as two scholars –Eiko Fried and Randolph Nesse – went back to the records of the 3700 outpatients in a previous study (STAR*D) to look for patterns of symptoms. Fried, E. I., & Nesse, R. M. (2015). Depression is not a consistent syndrome: An investigation of unique symptom patterns in the STAR*D study. Journal of Affective Disorders, 172, 96–102. (PDF)

Now, in most diseases in medicine there is a fairly clear pattern of symptoms. In mumps, almost all the clinical cases will have swollen parotid glands along with the fever and malaise of a classic viral infection. So if major depression is a real disease we should be able to find similar patterns: everyone sad, plus hopeless, plus lacking energy. You get the picture.

So what did the investigators find? ”Overall, we identified 1030 unique symptom profiles. Of these profiles, . . 83.9 percent were endorsed by five or fewer subjects. . . “ There were 501 profiles (48.6 percent) so unique as to be endorsed by only one patient. And “the most common symptom profile exhibited a frequency of only 1.8 percent.” In other words, the symptoms of the “depressed” patients were all over the place. There was no such thing as standard symptoms; they all had something different.

The authors concluded, “The substantial symptom variation among individuals who all qualify for one diagnosis calls into question the status of Major Depressive Disorder as a specific consistent syndrome and offers a potential explanation for the difficulty in documenting treatment efficacy.”

This latter sentence is a convoluted way of saying, “This is why so few patients with Major Depression respond to a specific treatment: Because there are a number of different diseases in the pot, not just one.” In fact, only about a fourth of the patients in the STAR*D study responded to treatments in the first round.

So the anti-DSM bandwagon is now gathering speed. “Schizophrenia” has come under the magnifying glass as a supposed unitary disease. The uniqueness of “bipolar disorder” as a separate affective disease is being increasingly challenged. The NIMH finds DSM-5 virtually useless in its own efforts to understand disease. Finally, I have thrown my own stone into these troubled waters with my new book, that will be out from Routledge two weeks from now, “What Psychiatry Left Out of the DSM-5: Historical Mental Disorders Today.” It is about the diseases that didn’t make it in but should have, and those that did make it in but shouldn’t have.