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
N1 - Publisher Copyright:
© 2018 The Author(s).
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.
KW - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Atorvastatin/therapeutic use
KW - Bipolar Disorder/drug therapy
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
U2 - 10.1186/s12888-018-1793-9
DO - 10.1186/s12888-018-1793-9
M3 - Article
C2 - 30012135
SN - 1471-244X
VL - 18
SP - 227
JO - BMC Psychiatry
JF - BMC Psychiatry
IS - 1
M1 - 227
ER -