Carl Lange: On Periodical Depressions and their pathogenesis. Speech delivered to the Medical Society of Copenhagen, January 19, 1886
Translated from the Original Danish into English by Johan Schioldann

Paul Grof’s comment


         Many thanks to Dr. Johan Schioldann for translating and for publishing this interesting historical paper by Carl Lange. It makes for fascinating reading. To discuss it briefly, I am first summing up his talk while omitting minutiae.

            In his lecture, Lange describes observations on hundreds of patients with recurrent depressions he followed as outpatients during the second half of the 19th century. These conditions affected patients from all walks of life, started between adolescence and late adulthood, and densely clustered in families. The frequency and length of episodes varied considerably. There were no striking gender differences, but pregnancy appeared to protect women from attacks during pregnancy.

            Several observations by Carl Lange struck me in particular. I think his description of the natural course of these untreated conditions is especially valuable. We do not see such cases anymore unadulterated and therefore in the current literature on mood disorders there are several wrong assumptions. To wit, Lange observed that the age of onset stretched from adolescence -but not earlier- and some patients became ill for the first time as late as in their 60s. The frequency of recurrences lessened later in life or even stopped. Pregnancy in these women was usually protective. We have made and reported the same observations in our studies of untreated course of mood disorders but you won't find them in the recent literature.

            The current assumptions are that mood disorders start early in life and that once a patient has had a few episodes of mood disorder, they will keep coming back indefinitely. As a result, the need for maintenance treatment is not regularly reassessed, and that's unfortunate and leads to overtreating.

            Reading the lecture makes it much easier to presume why Lange decided later to experiment with lithium in these depressions. Through “uric acid diathesis,” there was a mental link between these depressions and the disorders of joints where lithium was in therapeutic use at that time.

            His description makes it also easy to understand why he was later successful with lithium. It is striking how his description of these conditions - recurrent, wholly remitting, often periodic, clustering in families, untainted by comorbidities - resemble the current profile of excellent responders to lithium stabilization.

            If you wonder as I do, how is it possible that Lange did not observe hypomanias in these patients, I can only offer observations from the early lithium years, before our field became obsessed with bipolarity. Missing hypomanias was very common until psychiatrists learned how frequently patients presenting with recurrent depressions turned out having a bipolar type II illness.

            Hypomanias were missed for a variety of reasons: patients never came for treatment for hypomania, relatives considered elation an understandable reaction to recovering from depression, psychiatrists hospitalized patients for severe depressions only, etc.Things changed once psychiatry started zeroing in on bipolarity as something potentially well treatable. Even today you still find many patients with bipolar disorder treated with antidepressants only, disregarding hypomanias.

            Lange's careful, detailed description of his patients is very reminiscent of professors who taught us psychiatry in the 1950s. They could spend as much as an hour and a half analyzing an individual patient, even though they could not yet offer any proven treatment. How different from the colleagues who today spend up to 15 minutes checking off symptoms on the DSM list and then immediately prescribe psychotropics!

            Lange also correctly points out how challenging it is to evaluate the benefits of prophylactic treatment in these conditions - considerations so resonant with some of the heated debates raging in 1968–1976.

            Thank you so much, Drs. Schioldann and INHN for dusting off this mind-stimulating paper!


December 20, 2018