Barry Blackwell: The lithium Controversy in Historical Perspective. Collated

Janos Rado's additional final comment on Calcitonin in Lithium-induced nephrogenic diabetes insipidus

Janos Radó’s reply to Hector Warnes’ comments on his additional final comment


        Many thanks to Hector Warnes for his recent very interesting comments on my additional final comment of September 13, 2018.

        I absolutely agree with Hector Warnes that: “I would not take it lightly if the patient developed nephrogenic diabetes insipidus because of the kidney risks involved unless lithium has been the only mood stabilizing drug that kept the patient symptom free for many years.”

        In some patients treated more than10 years with lithium urinary concentrating ability decreases below plasma osmolality. Development of nephrogenic diabetes insipidus as a consequence of long-term lithium treatment is not a rarity anymore. In the two patients with severe disturbance in the renal concentrating operation of Hector Warnes it was a really wise decision to stop lithium therapy. In some cases withdrawal of lithium results in improvement in renal function, while in others lithium-induced nephrogenic diabetes insipidus remains irreversible (Radó and Zdravkova 1991,1993). Even in these cases of “lithium-induced permanent nephrogenic diabetes insipidus” therapy is not absolutely hopeless, there are several therapeutic options available, by which the rest of the patient during night can be somewhat secured by decreasing the polyuria. Thiazide diuretics, indomethacine, amiloride, desmopressin and most importantly combinations of them are our armamentarium in the alleviation of polyuria and polydipsia (Croft, Bedford, Leader and Walker 2018; Mizuno, Fujimoto, Sugiyama et al. 2003; Radó 2018; Radó 2019; Stasior, Kikeri, Duel and Seifter 1991; Weinstock and Moses 1990).

        It was the conclusion of our previous work that in such an important form of psychiatric treatment as lithium is, a serious side effect, the disturbance of water metabolism, can be alleviated by clever use of modern antidiuretic interventions. (Radó 2018)



Kalita-De Croft P, Bedford JJ, Leader JP, Walker RJ. Amiloride modifies the progression of lithium-induced renal interstitial fibrosis. Nephrology (Carlton). 2018 Jan;23(1):20-30.

Mizuno H, Fujimoto S, Sugiyama Y, Kobayashi M, Ohro Y, Uchida S, Sasaki S, Togari H. Successful treatment of partial nephrogenic diabetes insipidus with thiazide and desmopressin. Hormone Research 2003; 59(6) :297-300.

Radó’ J. Use of modern antidiuretic agents in the treatment of permanent lithium-induced nephrogenic diabetes insipidus (Administration of excessive doses of desmopressin resulted in clinically relevant antidiuresis, enhanced by indomethacine and abolished by calcitonine). January 25, 2018.

Radó JP, Zdravkova S. Lithium-induced chronic water-metabolism disorder (nephrogenic diabetes insipidus)]. Orv Hetil. 1991;132, 1987-90.

Radó J. Renal Toxicity of Lithium in Historical Perspective with Special Reference To Nephrogenic Diabetes Insipidus and its Treatment. May 2. 2019. 

Radó JP, Zdravkova S. Effect of Indomethacine and Calcitonin During Administration of 1-Deamino-8-D-Arginin-Vasopressin (dDAVP) on Free Water Clearance in Nephrogenic diabetes Insipidus (NDI). XIIth International Congress of Nephrology. June 13–18, 1993 Jerusalem, Israel.

Stasior DS, Kikeri D, Duel B, Seifter JL. Nephrogenic diabetes insipidus responsive to indomethacine plus dDAVP. New Eng J Med 1991; 324: 850-1. 

Weinstock RS Moses AM. Desmopressin and indomethacine therapy for nephrogenic diabetes insipidus in patients receiving lithium carbonate. South Med J 1990; 83: 1475-7.


August 15, 2019