Abstract
BackgroundLithium 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.MethodsWe 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.ResultsNot applicable.ConclusionThe 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 registrationClinicalTrials.govNCT02967653. Registered in February 2017.
Highlights
Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties
We describe the first randomized controlled trial (RCT) to evaluate the effectiveness of atorvastatin for treating Nephrogenic Diabetes Insipidus (NDI) in a population of lithium users
We opted for a urinary osmolality of < 600 mOsm/Kg: patients with < 600 mOsm/kg are at risk of future NDI-related complications, such as chronic kidney disease (CKD) and they constitute a large percentage of lithium users (50% of patients)
Summary
Lithium is the gold-standard treatment for bipolar disorder, is highly effective in treating major depressive disorder, and has anti-suicidal properties. 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. Despite the effectiveness of lithium, many clinicians avoid using it, with prescribing rates declining markedly in the past 2 decades, in America where only 8% of bipolar disorder patients receive lithium [9]. This is likely in large part due to the perception of serious potential adverse effects associated with lithium use compared to other treatment options [10]
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