Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: The protocol of a randomized controlled trial

Jocelyn Fotso Soh, Susana G. Torres-Platas, Serge Beaulieu, Outi Mantere, Robert Platt, I. Mucsi, Sybille Saury, Suzane Renaud, Andrea Levinson, Ana C. Andreazza, Benoit H. Mulsant, Daniel Müller, Ayal Schaffer, Annemiek Dols, Pablo Cervantes, Nancy C.P. Low, Nathan Herrmann, Birgitte M. Christensen, Francesco Trepiccione, Tarek RajjiSoham Rej

Research output: Contribution to journalArticle

Abstract

Background: Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin. Methods: We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline. Results: Not applicable. Conclusion: The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.

Original languageEnglish
Article number227
JournalBMC Psychiatry
Volume18
Issue number1
DOIs
Publication statusPublished - Jul 16 2018

Fingerprint

Nephrogenic Diabetes Insipidus
Lithium
Randomized Controlled Trials
Therapeutics
Chronic Renal Insufficiency
Osmolar Concentration
Placebos
Urine
Hypernatremia
Kidney
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Aquaporins
Atorvastatin Calcium
Major Depressive Disorder
Bipolar Disorder
Acute Kidney Injury
Gold
Fear
Canada
Cross-Sectional Studies

Keywords

  • Atorvastatin
  • Kidney function
  • Lithium
  • Nephrogenic diabetes insipidus
  • Placebo
  • Randomized clinical trial
  • Urinary osmolality

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus : The protocol of a randomized controlled trial. / Fotso Soh, Jocelyn; Torres-Platas, Susana G.; Beaulieu, Serge; Mantere, Outi; Platt, Robert; Mucsi, I.; Saury, Sybille; Renaud, Suzane; Levinson, Andrea; Andreazza, Ana C.; Mulsant, Benoit H.; Müller, Daniel; Schaffer, Ayal; Dols, Annemiek; Cervantes, Pablo; Low, Nancy C.P.; Herrmann, Nathan; Christensen, Birgitte M.; Trepiccione, Francesco; Rajji, Tarek; Rej, Soham.

In: BMC Psychiatry, Vol. 18, No. 1, 227, 16.07.2018.

Research output: Contribution to journalArticle

Fotso Soh, J, Torres-Platas, SG, Beaulieu, S, Mantere, O, Platt, R, Mucsi, I, Saury, S, Renaud, S, Levinson, A, Andreazza, AC, Mulsant, BH, Müller, D, Schaffer, A, Dols, A, Cervantes, P, Low, NCP, Herrmann, N, Christensen, BM, Trepiccione, F, Rajji, T & Rej, S 2018, 'Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: The protocol of a randomized controlled trial', BMC Psychiatry, vol. 18, no. 1, 227. https://doi.org/10.1186/s12888-018-1793-9
Fotso Soh, Jocelyn ; Torres-Platas, Susana G. ; Beaulieu, Serge ; Mantere, Outi ; Platt, Robert ; Mucsi, I. ; Saury, Sybille ; Renaud, Suzane ; Levinson, Andrea ; Andreazza, Ana C. ; Mulsant, Benoit H. ; Müller, Daniel ; Schaffer, Ayal ; Dols, Annemiek ; Cervantes, Pablo ; Low, Nancy C.P. ; Herrmann, Nathan ; Christensen, Birgitte M. ; Trepiccione, Francesco ; Rajji, Tarek ; Rej, Soham. / Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus : The protocol of a randomized controlled trial. In: BMC Psychiatry. 2018 ; Vol. 18, No. 1.
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T2 - The protocol of a randomized controlled trial

AU - Fotso Soh, Jocelyn

AU - Torres-Platas, Susana G.

AU - Beaulieu, Serge

AU - Mantere, Outi

AU - Platt, Robert

AU - Mucsi, I.

AU - Saury, Sybille

AU - Renaud, Suzane

AU - Levinson, Andrea

AU - Andreazza, Ana C.

AU - Mulsant, Benoit H.

AU - Müller, Daniel

AU - Schaffer, Ayal

AU - Dols, Annemiek

AU - Cervantes, Pablo

AU - Low, Nancy C.P.

AU - Herrmann, Nathan

AU - Christensen, Birgitte M.

AU - Trepiccione, Francesco

AU - Rajji, Tarek

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N2 - Background: Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. However, clinicians are increasingly avoiding lithium largely due to fears of renal toxicity. Nephrogenic Diabetes Insipidus (NDI) occurs in 15-20% of lithium users and predicts a 2-3 times increased risk of chronic kidney disease (CKD). We recently found that use of statins is associated with lower NDI risk in a cross-sectional study. In this current paper, we describe the methodology of a randomized controlled trial (RCT) to treat lithium-induced NDI using atorvastatin. Methods: We will conduct a 12-week, double-blind placebo-controlled RCT of atorvastatin for lithium-induced NDI at McGill University, Montreal, Canada. We will recruit 60 current lithium users, aged 18-85, who have indicators of NDI, which we defined as urine osmolality (UOsm) < 600 mOsm/kg after 10-h fluid restriction. We will randomize patients to atorvastatin (20 mg/day) or placebo for 12 weeks. We will examine whether this improves measures of NDI: UOsm and aquaporin (AQP2) excretion at 12-week follow-up, adjusted for baseline. Results: Not applicable. Conclusion: The aim of this clinical trial is to provide preliminary data about the efficacy of atorvastatin in treating NDI. If successful, lithium could theoretically be used more safely in patients with a reduced subsequent risk of CKD, hypernatremia, and acute kidney injury (AKI). If future definitive trials confirm this, this could potentially allow more patients to benefit from lithium, while minimizing renal risk.

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