A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users

TY - JOUR

T1 - A double-blind, randomized, placebo-controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users

AU - Fotso Soh, Jocelyn

AU - Beaulieu, Serge

AU - Trepiccione, Francesco

AU - Linnaranta, Outi

AU - Torres-Platas, Gabriela

AU - Platt, Robert W.

AU - Renaud, Suzane

AU - Su, Chien Lin

AU - Mucsi, Istvan

AU - D’Apolito, Luciano

AU - Mulsant, Benoit H.

AU - Levinson, Andrea

AU - Saury, Sybille

AU - Müller, Daniel

AU - Schaffer, Ayal

AU - Dols, Annemiek

AU - Low, Nancy

AU - Cervantes, Pablo

AU - Christensen, Birgitte M.

AU - Herrmann, Nathan

AU - Rajji, Tarek

AU - Rej, Soham

N1 - Funding Information: Authors thank the Kidney Foundation of Canada (Montr?al, QC. H3X 2H9) for their generous funding support without which this trial would not have been possible. Sponsors had no role in the design, analysis, interpretation and publication of the study. Publisher Copyright: © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - Objective: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. Method: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. Results: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, −35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were −0.13 L [95% CI, −0.54, 0.28] and 98.68 [95% CI, −190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). Conclusion: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

AB - Objective: Lithium remains an important treatment for mood disorders but is associated with kidney disease. Nephrogenic diabetes insipidus (NDI) is associated with up to 3-fold risk of incident chronic kidney disease among lithium users. There are limited randomized controlled trials (RCT) for treatments of lithium-induced NDI, and existing therapies can be poorly tolerated. Therefore, novel treatments are needed for lithium-induced NDI. Method: We conducted a 12-week double-blind pilot RCT to assess the feasibility and efficacy of 20 mg/d atorvastatin vs placebo in the treatment of NDI in chronic lithium users. Patients, recruited between September 2017 and October 2018, were aged 18 to 85, currently on a stable dose of lithium, and determined to have NDI. Results: Urinary osmolality (UOsm) at 12 weeks adjusted for baseline was not statistically different between groups (+39.6 mOsm/kg [95% CI, −35.3, 114.5] in atorvastatin compared to placebo groups). Secondary outcomes of fluid intake and aquaporin-2 excretions at 12 weeks adjusted for baseline were −0.13 L [95% CI, −0.54, 0.28] and 98.68 [95% CI, −190.34, 387.70], respectively. A moderate effect size was observed for improvements in baseline UOsm by ≥100 mOsm/kg at 12 weeks in patients who received atorvastatin compared to placebo (38.45% (10/26) vs 22.58% (7/31); Cohen's d = 0.66). Conclusion: Among lithium users with NDI, atorvastatin 20 mg/d did not significantly improve urinary osmolality compared to placebo over a 12-week period. Larger confirmatory trials with longer follow-up periods may help to further assess the effects of statins on NDI, especially within patients with more severe NDI.

KW - bipolar disorder

KW - kidney function

KW - lithium use

KW - nephrogenic diabetes insipidus

UR - http://www.scopus.com/inward/record.url?scp=85088089271&partnerID=8YFLogxK

U2 - 10.1111/bdi.12973

DO - 10.1111/bdi.12973

M3 - Journal article

C2 - 32621644

AN - SCOPUS:85088089271

SN - 1398-5647

VL - 23

SP - 66

EP - 75

JO - Bipolar disorders

JF - Bipolar disorders

IS - 1

ER -