Thomas A. Ban: Psychiatry for Neuropsychopharmacologists
2. From Kraepelin’s manic-depressive psychosis to Leonhard’s phasic and cycloid psychoses

Peter R. Martin’s comment


It is indeed a pleasure to read such an erudite treatment of the historical developments in conceptualization of “manic depressive psychosis” (MDP).  Ban describes, within context of neuroscientific advances of their day, the contributions to current understanding of MDP of scholars of mental pathology over the last two centuries .  After Wernicke’s “elementary symptom” approach, Kraepelin shifted emphasis from a cross-sectional perspective of mental disorders to one encompassing characteristics of their origin, course and outcome.  Notions of etiology and expressed psychopathology subsequently entered the mix, including the idea that MDP was an “endogenous psychosis whose appearance is generally unrelated to external circumstances”.  The concepts of polarity and the “polymorphous” or “monomorphous” nature of either depression or mania as attributed to Kleist and Leonhard are then discussed.  Finally, Ban describes appropriate diagnostic instruments that presumably are needed for neuropsychopharmacologic characterization and appropriate selection of the most effective psychopharmacologic treatments.

I believe Ban’s historical discussion contains one significant lacuna. (I acknowledge that this opinion is strongly influenced by my own clinical experience focused on addiction psychiatry.)  It is difficult to consider the intricacies of MDP without mention of the finding that 60 to 80 percent of those with MDP can also be diagnosed with alcohol or drug use disorders (Rich and Martin 2014).  MDP with and without alcohol/drug use disorders seem to be very different expressions of the same disorder.  However, it seems the typical course of MDP may include an inexorable intertwining with alcohol/drug use disorders. Therefore, it is difficult to understand why most research on the neurobiology and treatment of MDP is conducted in the minority of MDP patients, namely those in whom alcohol/drug use disorder has been excluded.

Alcohol/drug use disorder patients diagnosed with co-occurring MDP typically have a “polymorphous fluctuating disease picture”, described by Ban as one of the criteria for MDP of the DCR Budapest-Nashville; namely, a “multiform, variable disease picture in which different symptoms and/or syndromes prevail at different times. Behavior is characterized by its rapid and frequent variations alternating between extreme (opposite poles).”  The essence is mood instability, further accentuated by the alcohol/drug use, initially intended by the affected individual as a means of self-medication. The neurobiology and treatment of MDP associated with alcohol/drug use disorders likely differs from MDP that occurs alone, although this has yet to be extensively studied.  I have repeatedly observed that responsiveness to lithium is not as likely in this population and have found better outcomes with anticonvulsants and/or neuroleptics.  In part, this might be explained by the efficacy of anticonvulsants in reducing craving and relapse to alcohol and other drugs such as stimulants. Which, of course, leads to the obverse question of how common is alcohol/drug use disorders without mood instability and the etiology of mood instability in alcohol/drug use disorders?  Could it be that MDP is characterized by alcohol/drug use disorder and those with MDP but no alcohol/drug use do not represent the natural course of MDP?  These questions will never be satisfactorily answered unless academics and the pharmaceutical industry make a serious effort to study alcohol/drug use disorders in MDP.  Most important we must recognize the importance of MDP in the etiology of alcohol/drug use disorders and vice versa.



Rich SJ, Martin PR (2014). Co-occurring psychiatric disorders and alcoholism. In: Sullivan EV, Pfefferbaum A (eds) Handbook of Clinical Neurology Alcohol and the Nervous System. Elsevier, pp 573-588.


Peter R. Martin

July 21, 2016