Janusz Rybakowski: Lithium therapy- a personal tale of the recent decade 


Paul Grof’s comment


        Professor Rybakowski was the head of the Department of Psychiatry at Poznan university until 2016. Over the past 50 years there, much of his research focused on lithium's clinical use and possible mechanisms of action. From his numerous publications throughout his career, he selected for this book 39 papers he published as the leading author during the recent decade.  The scope of the work and its comprehensive nature are admirable.

        As this volume is rich and varied in its content, I thought I should review it by choosing the most significant points. At a major journal, I served long in charge of book reviews where I learned that excellent reviews could be written only about books with only one dominating topic.  Multi-topic books are nearly impossible to represent properly. But the rich content of Rybakowski's book is close to my heart. Year after year, I followed the mounting of his material as he regularly presented his innovative studies at conferences and they attracted much interest.

        The book opens with his personal tale of lithium research conducted during the past decade. Rybakowski's investigations have been intensely involved in the essential clinical aspects of lithium treatment, stretching from guides for prescribers to the inquiry of adverse effects, the cognitive functioning of the patients and the thyroid changes (I counted 11 articles).

        The kidney function has received particular attention (with seven articles) and for a good reason. A number of Rybakowski's patients have been receiving maintenance lithium for up to 50 years.  This cohort on lithium monotherapy is unique, possibly not available anywhere else, and requires special attention. Unlike during the first two decades of lithium monotherapy, when glomerular filtration remains intact, after four decades a fair proportion of patients start showing the observable reduction. No one else has so far published on this topic, "ultra-long lithium monotherapy." I doubt there are too many investigators who have similar material.

        While there is no relevant evidence that glomerular filtration in lithium-treated patients is adversely affected during the first two decades of treatment, Rybakowski's observations about "ultra-long" treatment should call for concern. In the next couple of decades, many other investigators will gradually encounter this problem and here professor Rybakowski can offer invaluable observations based on his own experiences.  More patience on “ultra-long lithium treatment" will be seen, most likely with reduced glomerular filtration. It is urgent that we start exploring lithium treatment strategies that minimize or avoid this problem.

        Rybakowski also guided a very productive group of genetic researchers and six of their papers are included here. Molecular genetic research of lithium-relevant candidate genes, while productive, is still in its early stages. Some associations have been reported between lithium's prophylactic response and the polymorphism of various candidate genes, but rarely have the findings been replicated. A valuable paper on the offspring of lithium-treated parents is added and an enormously interesting chapter on lithium treatment in literature and art.

        Four more papers deal with another particular interest of the author, the features of lithium responders. Inspired partly by the earlier investigations of Hagop Akiskal, Rybakowski has explored and confirmed, in particular, the relationship between lithium response and temperament.

        To complete the investigative journey, his original works on antiviral, antiherpes and neuroprotective properties of lithium are outlined, as well as lithium-driven explorations of biochemical activities embryonic-like stem cells and mRNA and glial markers.

        Through all his clinical and research activities, Rybakowski became part of lithium history. This fact was well expressed when the ISBD awarded him the Mogens Schou Research Award. Thus, naturally, his book also addresses historical figures in three of his papers.

        I want to end my review of Professor Rybakowski's personal tale with my own account. I had a special opportunity to see the unique clinical material, which is the basis of the research described in professor Rybakowski's book. In 1998 I was given a task to assess all IGSLI lithium maintenance responders suitable for a collaborative genetic study of lithium response. The purpose was to review all patients included in the study by one person to achieve clinical homogeneity.

        During the nearly 60 years, I have visited many setups treating and investigating patients with lithium. However, this one stood out by combining excellent research quality with simplicity.

        Each patient's chart was hand-written and deposited in a simple brown envelope, but each demonstrated crystal-clear patients successfully treated by lithium monotherapy for decades. The previous course of illness and family history were precisely described in detail for each case.

        Even a quarter of a century later, I am still very impressed by this unforgettable clinical research material. These Poznan observations contrasted sharply with other setups that I have visited in North America where the information is neatly saved in a computerized database, but patients have been treated with a cocktail of complex polypharmacy that makes it impossible to evaluate what role, if any, has lithium played and what its benefits and side-effects might have been.


January 27, 2022