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, Istvan Mucsi, Sybille Saury, Suzane Renaud, Andrea Levinson, Ana C Andreazza, Benoit H Mulsant, Daniel Müller, Ayal Schaffer, Annemiek Dols, Pablo Cervantes, Nancy Cp Low, Nathan Herrmann, Birgitte M Christensen, Francesco Trepiccione, Tarek Rajji & 1 others Soham Rej

Research output: Contribution to journalArticleAcademicpeer-review

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 - 16 Jul 2018

Cite this

Fotso Soh, Jocelyn ; Torres-Platas, Susana G ; Beaulieu, Serge ; Mantere, Outi ; Platt, Robert ; Mucsi, Istvan ; Saury, Sybille ; Renaud, Suzane ; Levinson, Andrea ; Andreazza, Ana C ; Mulsant, Benoit H ; Müller, Daniel ; Schaffer, Ayal ; Dols, Annemiek ; Cervantes, Pablo ; Low, Nancy Cp ; 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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title = "Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial",
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.",
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author = "{Fotso Soh}, Jocelyn and Torres-Platas, {Susana G} and Serge Beaulieu and Outi Mantere and Robert Platt and Istvan Mucsi and Sybille Saury and Suzane Renaud and Andrea Levinson and Andreazza, {Ana C} and Mulsant, {Benoit H} and Daniel M{\"u}ller and Ayal Schaffer and Annemiek Dols and Pablo Cervantes and Low, {Nancy Cp} and Nathan Herrmann and Christensen, {Birgitte M} and Francesco Trepiccione and Tarek Rajji and Soham Rej",
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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, NC, 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, https://doi.org/10.1186/s12888-018-1793-9

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, Istvan; Saury, Sybille; Renaud, Suzane; Levinson, Andrea; Andreazza, Ana C; Mulsant, Benoit H; Müller, Daniel; Schaffer, Ayal; Dols, Annemiek; Cervantes, Pablo; Low, Nancy Cp; 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 journalArticleAcademicpeer-review

TY - JOUR

T1 - Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus

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, Istvan

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 Cp

AU - Herrmann, Nathan

AU - Christensen, Birgitte M

AU - Trepiccione, Francesco

AU - Rajji, Tarek

AU - Rej, Soham

PY - 2018/7/16

Y1 - 2018/7/16

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.

AB - 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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KW - Aged

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KW - Canada/epidemiology

KW - Cross-Sectional Studies

KW - Depressive Disorder, Major/drug therapy

KW - Diabetes Insipidus, Nephrogenic/chemically induced

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Kidney/drug effects

KW - Lithium Compounds/adverse effects

KW - Male

KW - Middle Aged

KW - Young Adult

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