Janos Rado. Renal toxicity of lithium in historical perspective with special reference to nephrogenic diabetes insipidus and its treatment.


Janusz Rybakowski’s response to Janos Radó’s reply


         I was greatly flattered by the appraisal of my comment by Janos Radó. It seems that the bottom line for both of us is to efficiently alleviate possible renal obstacles to long-term lithium treatment, be it nephrogenic diabetes insipidus or lithium-induced nephropathy. We concur with the notion that lithium should be used more frequently and, by doing so, it would be able to help the larger number of patients.

         While lithium is the drug of choice for preventing recurrences in bipolar (and probably also unipolar) mood disorder, the fringe benefits of lithium therapy should also be emphasized. These are connected with anti-suicidal, antiviral and neuroprotective properties of this ion. Among all mood-stabilizing drugs, lithium is the most powerful for preventing suicidal behavior (Cipriani, Hawton, Stockton and Geddes 2013). The antiviral effect of lithium was demonstrated by showing a reduction of labial herpers frequency in long-term lithium-treated patients (Rybakowski and Amsterdam 1991). Finally, neuroprotective effects of lithium have been demonstrated such as increasing cerebral volume, decreasing risk of dementia as well as promising results in Alzheimer's disease (Rybakowski, Suwalska and Hajek 2018). Interestingly, the effect of lithium in dementia might be connected with its action against herpes viruses (Rybakowski 2019). A recent paper of Van Gestel, Franke, Petite et al. (2019) could also be recalled showing that lithium-treated bipolar patients show the features of decreased brain aging.

         It should be hoped that disseminating knowledge on the efficient managing of lithium-induced renal side effects could contribute to more common application of this therapeutic ion in mood disorders.



Cipriani A, Hawton K, Stockton S, Geddes JR. Lithium in the prevention of suicide in mood disorders: updated systematic review and meta-analysis. Br Med J 2013;346:f3646.

Van Gestel H, Franke K, Petite J, Slaney C, Garnham J, Helmick C, Johnson K, Uher R, Alda M, Hajek T. Brain age in bipolar disorders: Effects of lithium treatment. Aust N Z J Psychiatry 2019 Jun 27: 4867419857814. [Epub ahead of print].

Rybakowski JK, Amsterdam JD. Lithium prophylaxis and recurrent labial herpes infections. Lithium 1991;2:43-7.

Rybakowski JK, Suwalska A, Hajek T. Clinical perspectives of lithium's neuroprotective effect. Pharmacopsychiatry 2018;51:194-99.

Rybakowski JK. Commentary: Corroboration of a major role for Herpes Simplex Virus Type 1 in Alzheimer's disease. Front Aging Neurosci 2019;10:433.


November 14, 2019