Brian Shine1, Rebecca F McKnight2, Laurence Leaver3, John R Geddes4. 1. John Radcliffe Hospital, Oxford, UK. 2. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK. Electronic address: Rebecca.mcknight@psych.ox.ac.uk. 3. Jericho Health Centre, New Radcliffe House, Oxford, UK. 4. Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Abstract
BACKGROUND: Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. METHODS: In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. FINDINGS: Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. INTERPRETATION: Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. FUNDING: None.
BACKGROUND:Lithium is a widely used and highly effective treatment for mood disorders, but causes poorly characterised adverse effects in kidney and endocrine systems. We aimed to analyse laboratory information system data to determine the incidence of renal, thyroid, and parathyroid dysfunction associated with lithium use. METHODS: In a retrospective analysis of laboratory data from Oxford University Hospitals National Health Service Trust (Oxfordshire, UK), we investigated the incidence of renal, thyroid, and parathyroid dysfunction in patients (aged ≥18 years) who had at least two creatinine, thyrotropin, calcium, glycated haemoglobin, or lithium measurements between Oct 1, 1982, and March 31, 2014, compared with controls who had not had lithium measurements taken. We used survival analysis and Cox regression to estimate the hazard ratio (HR) for each event with lithium use, age, sex, and diabetes as covariates. FINDINGS: Adjusting for age, sex, and diabetes, presence of lithium in serum was associated with an increased risk of stage three chronic kidney disease (HR 1·93, 95% CI 1·76-2·12; p<0·0001), hypothyroidism (2·31, 2·05-2·60; p<0·0001), and raised total serum calcium concentration (1·43, 1·21-1·69; p<0·0001), but not with hyperthyroidism (1·22, 0·96-1·55; p=0·1010) or raised adjusted calcium concentration (1·08, 0·88-1·34; p=0·4602). Women were at greater risk of development of renal and thyroid disorders than were men, with younger women at higher risk than older women. The adverse effects occurred early in treatment (HR <1 for length of treatment with lithium). Higher than median lithium concentrations were associated with increased risk of all adverse outcomes. INTERPRETATION:Lithium treatment is associated with a decline in renal function, hypothyroidism, and hypercalcaemia. Women younger than 60 years and people with lithium concentrations higher than median are at greatest risk. Because lithium remains a treatment of choice for bipolar disorder, patients need baseline measures of renal, thyroid, and parathyroid function and regular long-term monitoring. FUNDING: None.
Authors: Rebecca F McKnight; Saïk J G N de La Motte de Broöns de Vauvert; Edward Chesney; Ben H Amit; John Geddes; Andrea Cipriani Journal: Cochrane Database Syst Rev Date: 2019-06-01
Authors: Victor M Castro; Ashlee M Roberson; Thomas H McCoy; Anna Wiste; Andrew Cagan; Jordan W Smoller; Jerrold F Rosenbaum; Michael Ostacher; Roy H Perlis Journal: Neuropsychopharmacology Date: 2015-08-21 Impact factor: 7.853
Authors: Ahsan Habib; R Douglas Shytle; Darrell Sawmiller; Selina Koilraj; Sadia Afrin Munna; David Rongo; Huayan Hou; Cesario V Borlongan; Glenn Currier; Jun Tan Journal: J Neurosci Res Date: 2019-05-17 Impact factor: 4.164
Authors: Katherine E Burdick; Caitlin E Millett; Manuela Russo; Martin Alda; Ney Alliey-Rodriguez; Amit Anand; Yokesh Balaraman; Wade Berrettini; Holli Bertram; Joseph R Calabrese; Cynthia Calkin; Carla Conroy; William Coryell; Anna DeModena; Scott Feeder; Carrie Fisher; Nicole Frazier; Mark Frye; Keming Gao; Julie Garnham; Elliot S Gershon; Kara Glazer; Fernando S Goes; Toyomi Goto; Gloria J Harrington; Petter Jakobsen; Masoud Kamali; Marisa Kelly; Susan Leckband; Else Marie Løberg; Falk W Lohoff; Adam X Maihofer; Michael J McCarthy; Melvin McInnis; Gunnar Morken; Caroline M Nievergelt; John Nurnberger; Ketil J Oedegaard; Abigail Ortiz; Megan Ritchey; Kelly Ryan; Martha Schinagle; Candice Schwebel; Martha Shaw; Paul Shilling; Claire Slaney; Emma Stapp; Bruce Tarwater; Peter Zandi; John R Kelsoe Journal: Neuropsychopharmacology Date: 2020-04-29 Impact factor: 7.853
Authors: Rachael W Taylor; Lindsey Marwood; Emanuella Oprea; Valeria DeAngel; Sarah Mather; Beatrice Valentini; Roland Zahn; Allan H Young; Anthony J Cleare Journal: Int J Neuropsychopharmacol Date: 2020-12-03 Impact factor: 5.176