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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Jocelyn Fotso Soh, McGill University, Jewish General Hospital
  • ,
  • Serge Beaulieu, McGill University
  • ,
  • Francesco Trepiccione, University of Naples Federico II
  • ,
  • Outi Linnaranta, McGill University
  • ,
  • Gabriela Torres-Platas, McGill University
  • ,
  • Robert W. Platt, McGill University
  • ,
  • Suzane Renaud, McGill University
  • ,
  • Chien Lin Su, McGill University
  • ,
  • Istvan Mucsi, University of Toronto
  • ,
  • Luciano D’Apolito, Biogem S.c.a.r.l.
  • ,
  • Benoit H. Mulsant, University of Toronto
  • ,
  • Andrea Levinson, University of Toronto
  • ,
  • Sybille Saury, McGill University
  • ,
  • Daniel Müller, University of Toronto
  • ,
  • Ayal Schaffer, University of Toronto
  • ,
  • Annemiek Dols, Amsterdam UMC
  • ,
  • Nancy Low, McGill University
  • ,
  • Pablo Cervantes, McGill University
  • ,
  • Birgitte M. Christensen
  • Nathan Herrmann, University of Toronto
  • ,
  • Tarek Rajji, University of Toronto
  • ,
  • Soham Rej, McGill University, Jewish General Hospital

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.

Original languageEnglish
JournalBipolar disorders
Volume23
Issue1
Pages (from-to)66-75
Number of pages10
ISSN1398-5647
DOIs
Publication statusPublished - Feb 2021

    Research areas

  • bipolar disorder, kidney function, lithium use, nephrogenic diabetes insipidus

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