Thomas A. Ban
Neuropsychopharmacology in Historical Perspective.

Education in the field in the Post-Psychopharmacology Era

Collated 39


Thomas A. Ban: Lithium in Psychiatry in Historical Perspective

Dedication and Preface



         To Gyorgy (George) Sandor, my service chief and teacher in 1955 at the National Institute of Nervous and Mental Diseases in Budapest. It was from Sandor that I first heard about the therapeutic potential of lithium in manic-depressive patients. Far ahead of his time, he already used lithium in maintenance treatment of some of his patients and monitored blood levels to keep the substance in the safe therapeutic range.


         “Lithium in Psychiatry in Historical Perspective” is a collection of selected postings from INHN’s website. To provide  readily accessible information on the history of the clinical development of the substance in psychiatry  the postings are presented under eight headings: 1. discovery, 2. introduction, 3. verification, 4. controversy, 5. re-evaluation, 6. safety, 7. action and 8. indications.

         The potential use of lithium in “mania” was discovered by William T. Hammond (1871) and in “periodic depression” by Carl Lange in the mid and late-19th century, respectively. There are two postings included in the collection relevant to this topic: 1. Johan Schioldann’s comment on William T. Hammond and 2. Carl Lange’s speech “On Periodical Depressions and Their Pathogenesis,” in Johan Schioldann’s translation from Danish into English. Schioldann’s comment on Hammond was posted in BOOKS on September 20, 2018, and Lange’s speech in PERSPETIVE on August 16, 2018.

         Instrumental to the introduction of lithium into treatment was Edward Trautner’s determination of the effective dose range in which lithium can be used safely. He carried out the crucial study with Charles Noack, his junior associate, and their  paper was published in 1951, two years after John Cade’s (1949)  report of successful treatment of manic patients with lithium. There are four postings in the collection relevant to this topic: John Cade’s and Edward Trautner’s biographies, written by Samuel Gershon, posted in PROFILES on August 1, 2013; Sam Gershon’s autobiographic account, Events and Memories,  posted in BIOGRAPHIES on June 25, 2015; and Gershon’s Lithium History, posted in CONTROVERSIES  on May 1, 2018.

         The therapeutic effect of Lithium in “mania” was verified by Mogens Schou and his associates (1954) in the mid-1950s. Their findings set the stage for the clinical development of the substance. There are three postings in the collection relevant to this topic: Mogens Schou’s autobiography, My journey with Lithium, presented by Johan Schioldann in BIOGRAPHIES on August 10, 2018, and Paul Grof’s  and Janusz Rybakowski’s comment on it,  posted  on January 10, 2019, and October 24, 2019, respectively.

         Acceptance of lithium treatment was delayed by a controversy in the mid-1960s, triggered by Blackwell and Shepherd’s 1968 paper in the Lancet in which they referred to Baastrup and Schou’s (1967) findings that lithium has prophylactic effect in manic depressive patients, as “another therapeutic myth.” The controversy concluded with Baastrup and Schou’s reply, published in 1968, in which they provided further substantiation to lithium’s prophylactic effect (Baastrup and Schou 1968a,b). There are four postings in the collection relevant to this topic: Barry Blackwell’s essay, The lithium controversy, a historical autopsy, posted in CONTROVERSIES on June 14, 2014; Paul Grof’s  and Jules Angst’s comments on it,  both posted on January 22, 2015; and Blackwell’s reply to both, posted on February 5, 2015. 

         In the 1980s lithium was re-evaluated and its place in the treatment of bipolar disorder (manic-depressive psychosis) consolidated. There are three postings in the collection  relevant to this topic: Paul Grof’s comment, More hindsight thought on Barry Blackwell’s comments on Mogens Schou’s My journey with lithium, posted in BIOGRAPHIES on November 7, 2019;  Barry Blackwell’s review of Johan Schioldann’s (2009) History of the Introduction of Lithium into Medicine and Psychiatry: Birth of Modern Psychopharmacology 1949 posted in BOOKS on September 14, 2017, and  Johan Schioldann’s comment, Ripostes and Annotations, on Blackwell’s review, posted on February 15, 2018.

         By the time the re-evaluation concluded, lithium has become lifetime treatment for patients with “bipolar disorder” and with the prolonged use of the substance its anti-vasopressin action, causing polyuria and nephrogenic diabetes insipidus in vulnerable patients, had become a safety concern.  Spearheaded by the research of Janos Radó, by the end of the second decade of the 21st century, renal toxicity of lithium could be successfully treated and prevented; the safety concerns about the chronic use of lithium, at least in terms of its renal toxicity, has been resolved.   There are five postings by Radó included in this collection relevant to this topic. One, Mechanism of lithium-induced polyuria in historical perspective,” posted in PERSPECTIVE on July 4, 2019; and four, Calcitonin in nephrogenic diabetes insipidusRenal toxicity of lithium in historical perspective with special reference to nephrogenic diabetes insipidus, Desmopressin may counteract polyuria in lithium-induced nephrogenic diabetes insipidus. Review of the literature and Use of modern antidiuretic agents in lithium-induced nephrogenic diabetes insipidus, posted in CONTROVERSIES, on January 25, 2018, September 13, 2018, May 2, 2019, and July 18, 2019, respectively.

         Throughout the years the mode of action of lithium has been extensively studied. Yet, in this selection, information on its possible mode of action is restricted to its effect on the “purinergic system” presented in two postings: 1.  Magda Malewska-Kasprzak, Agnieszka Permoda-Osip and Janusz Rybakowski’s (2018) treatise,  Disturbances of the purinergic system in affective disorders and schizophrenia, and 2.  Janusz K. Rybakowski’s Additional information: A commentary on Walter Felber’s paper on Lithium prevention of depression 100 years ago -- an ingenious misconception, published in 1987.  Both were posted in CONTROVERSIES on December 13, 2018, and February 21, 2019, respectively.

         The therapeutic indication of lithium extended, after its introduction, from the treatment of “manic excitement” to the acute, maintenance and prophylactic treatment of “manic-depressive psychosis” referred to by that time as “bipolar disorder” in consensus-based classifications. The heterogeneity in responsiveness to lithium in bipolar patients was recognized early but it has remained an open question whether populations derived by psychiatric nosology and psychopathology would provide more homogenous populations, in terms of responsiveness to lithium, than the consensus-based diagnosis of “bipolar disorder.” There are two postings by Thomas Ban which provide relevant information to this topic: 1. Development of the diagnostic concept of Manic-Depressive Psychosis in Emil Kraepelin’s classifications, posted in ARCHIVES (Ban Collection) on November 5, 2015, and From Emil Kraepelin’s Manic-Depressive Psychosis to Karl Leonhard’s Phasic and Cycloid Psychoses posted in COURSES (Central Office) on April 16, 2016.



Baastrup PC, Schou M. Lithium as a prophylactic agent: Its effect against recurrent depressions and manic-depressive psychosis. Arch Gen. Psychiatr. 1967; 16:162-72. 

Baastrup PC, Schou M. Prophylactic lithium. Lancet 1968a; I:1419-22. 

Baastrup PC, Schou M. Prophylactic lithium. Lancet 1968b; II:340-50.

Blackwell B, Shepherd M. Prophylactic lithium: Another therapeutic myth? An examination of the evidence to date. Lancet 1968; I: 968-71. 

Cade JF. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2:349-52.

Hammond WA. Treatise on Diseases of the Nervous System. London:Lewis, 1882. 

Malewska-Kasprzak M, Permoda-Osip A, Rybakowski J. Disturbances of the purinergic system in affective disorders and schizophrenia. Psychiatr Pol 2018; 52. 

Noack D, Trautner EM.  The lithium treatment of maniacal psychosis.  Med J Austr 1951; 2:218-22. 

Schioldann J. History of the Introduction of Lithium into Medicine and Psychiatry. Birth of Modern Psychopharmacology 1949. Adelaide: Adelaide Academic Press; 2009. 

Schou M, Juel-Nielsen N, Strömgren E, Voldby H. The treatment of manic psychoses by the administration of lithium salts. J. Neurol. Neurosurg. Psychiatr. 1954; 17:250-60.


December 9, 2019

            July 9, 2020