Janusz Rybakowski: 120 years of the Kraepelinian dichotomy of "endogenous psychoses" in historical perspective

Edward Shorter’s comment

         Professor Rybakowski holds the professorship of psychiatry at Poznan University of Medical Sciences and is among the most distinguished European students of psychopharmacology. And his remarks about the Kraepelinian “dichotomy” are well worth attention. But there is a problem. It is the problem of people bellowing at each other through a megaphone without really hearing the other megaphone.

         The Kraepelinian megaphone made two arresting assertions:

1.That a firewall existed between madness and mood disorders, which is to say, between dementia praecox and manic-depressive insanity. That firewall has been preserved in DSM.

2.That all of the mood disorders of whatever polarity belong in a single basin: the manic-depressive basin.

         Now, other megaphones have ignored some of the Kraepelinian megaphone. Professor Rybakowski believes, to some extent, in the Kraepelin “firewall,” which he and others call the “dichotomy.” But Professor Rybakowski does not believe in the other great Kraepelinian proposition, the single pool of mood disorders, because he accepts “bipolar disorder” as a separate illness. (It is, by the way, incorrect to say that our bipolar disorder is a lineal descendant of Kraepelin’s manic-depressive insanity: we accept unipolar depression [“major depression”] as an entirely separate entity. Kraepelin, of course, lumped it into the manic-depressive basin). It was not Kraepelin but Karl Leonhard who created the distinction between the depression of “bipolar disorder” and the depression of unipolar disorder.

         So, we are off to a bad start, treating bipolar disorder as a separate entity. We stumble further as we treat “schizophrenia” as a separate entity. These are not disease entities as found in nature but the product of decades of accreting unwisdom, much like viewing the eddying tide and believing that it is a battleship. Kraepelin’s historic mistake was erecting the firewall. So, associating distinctive patterns of neurotransmitter activity and treatment response with these artifactual entities is bound to end in tears. What solid pieces of knowledge do we possess?

1.There is virtually no specificity of response in psychopharmacology. Everything works grosso modo on everything. Most agents are panaceas. (Lithium is in fact effective in manic psychosis.) One has only to look at the steady expansion of indications in the so-called “second-generation antipsychotics” to understand the correctness of this proposition.

2.Depression and schizophrenia are hopelessly intertwined. Schizophrenic episodes can begin with depression; depression can occur throughout schizophrenia; depression can persist after the “schizophrenia” has resolved.

3.Antipsychotics have a strong antidepressant activity. Chlorpromazine was seen for years as an effective agent in depression, psychotic or otherwise, and it was only a bureaucratic exercise at FDA called “Drug Efficacy Study Implementation” (DESI) that ended the antidepressant role of the antipsychotics.

4.It is mainly as a result of the marketing activities of Pharma that this steady expansion of indications has occurred. We have known all along that Risperdal, Zyprexa and so forth were panaceas because the sales representatives assured us, in whispered murmurs, that this was so. Only when the companies performed the incredibly expensive RCTs was the obvious confirmed.

5.As for specificity of genetics, “polygenic response” is merely a euphemistic way of saying that no one has found a distinctive genetic profile for any DSM disease entity. There is no mystery about this. We don’t have the proper endotypes, and without discovering endotypes as they exist in nature, we won’t have specific genetic pictures.

         In other words, much of the “literature” of the last 30 years has really been a waste of time. Effective means of differentiating disease classes, such as pharmaco-EEG, have been cast aside in favor of an unproductive preoccupation with neurotransmitters. It is a preoccupation that has led neither to the discovery of new diseases nor of new agents — except for those diseases, such as “postpartum depression,” that can be marketed profitably.

         It is dismaying to write so negatively, but if we want to move the ball down the field — as Barney Carroll used to say — we have to look Nature in the face.

December 26, 2019