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 (...
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| Format: | Article |
| Language: | English |
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BMC
2018-07-01
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| Series: | BMC Psychiatry |
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| Online Access: | http://link.springer.com/article/10.1186/s12888-018-1793-9 |
| _version_ | 1828421421197426688 |
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| author | 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 Soham Rej |
| author_facet | 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 Soham Rej |
| author_sort | Jocelyn Fotso Soh |
| collection | DOAJ |
| description | 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. Trial registration ClinicalTrials.gov NCT02967653. Registered in February 2017. |
| first_indexed | 2024-12-10T15:29:17Z |
| format | Article |
| id | doaj.art-b1bbd3ac2f414c68ab2ac7372bc7c78e |
| institution | Directory Open Access Journal |
| issn | 1471-244X |
| language | English |
| last_indexed | 2024-12-10T15:29:17Z |
| publishDate | 2018-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Psychiatry |
| spelling | doaj.art-b1bbd3ac2f414c68ab2ac7372bc7c78e2022-12-22T01:43:26ZengBMCBMC Psychiatry1471-244X2018-07-011811710.1186/s12888-018-1793-9Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trialJocelyn Fotso Soh0Susana G. Torres-Platas1Serge Beaulieu2Outi Mantere3Robert Platt4Istvan Mucsi5Sybille Saury6Suzane Renaud7Andrea Levinson8Ana C. Andreazza9Benoit H. Mulsant10Daniel Müller11Ayal Schaffer12Annemiek Dols13Pablo Cervantes14Nancy CP Low15Nathan Herrmann16Birgitte M. Christensen17Francesco Trepiccione18Tarek Rajji19Soham Rej20Geri-PARTy Research Group, Jewish General Hospital/Lady Davis Institute, McGill UniversityGeri-PARTy Research Group, Jewish General Hospital/Lady Davis Institute, McGill UniversityDouglas Mental Health University Institute and Department of Psychiatry, McGill UniversityDouglas Mental Health University Institute and Department of Psychiatry, McGill UniversityDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University Health CentreDivision of Nephrology, University Health Network, University of Toronto (UofT)Douglas Mental Health University Institute and Department of Psychiatry, McGill UniversityDouglas Mental Health University Institute and Department of Psychiatry, McGill UniversityDepartment of Psychiatry, Centre for Addiction and Mental Health & Department of Psychiatry, University of TorontoDepartment of Psychiatry, Centre for Addiction and Mental Health & Department of Psychiatry, University of TorontoDepartment of Psychiatry, Centre for Addiction and Mental Health & Department of Psychiatry, University of TorontoDepartment of Psychiatry, Centre for Addiction and Mental Health & Department of Psychiatry, University of TorontoDepartment of Psychiatry, Sunnybrook Research Institute, University of TorontoDepartment of Psychiatry, GGZDepartment of Psychiatry, McGill University Health CentreDepartment of Psychiatry, McGill University Health CentreDepartment of Psychiatry, Sunnybrook Research Institute, University of TorontoDepartment of Biomedicine, University of AarhusDivision of Nephrology, University of NaplesDepartment of Psychiatry, Centre for Addiction and Mental Health & Department of Psychiatry, University of TorontoGeri-PARTy Research Group, Jewish General Hospital/Lady Davis Institute, McGill UniversityAbstract 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. Trial registration ClinicalTrials.gov NCT02967653. Registered in February 2017.http://link.springer.com/article/10.1186/s12888-018-1793-9LithiumNephrogenic diabetes insipidusKidney functionAtorvastatinPlaceboUrinary osmolality |
| spellingShingle | 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 Soham Rej Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial BMC Psychiatry Lithium Nephrogenic diabetes insipidus Kidney function Atorvastatin Placebo Urinary osmolality |
| title | Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial |
| title_full | Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial |
| title_fullStr | Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial |
| title_full_unstemmed | Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial |
| title_short | Atorvastatin in the treatment of Lithium-induced nephrogenic diabetes insipidus: the protocol of a randomized controlled trial |
| title_sort | atorvastatin in the treatment of lithium induced nephrogenic diabetes insipidus the protocol of a randomized controlled trial |
| topic | Lithium Nephrogenic diabetes insipidus Kidney function Atorvastatin Placebo Urinary osmolality |
| url | http://link.springer.com/article/10.1186/s12888-018-1793-9 |
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