title: Long-term, low-dose lithium treatment does not impair renal function in the elderly: a 2-year randomized, placebo-controlled trial followed by single-blind extension.
abstract: BACKGROUND
  Recent studies evaluated the disease-modifying properties of lithium in mild cognitive impairment and dementia. Although potentially effective for these purposes, chronic lithium use in regard to safety in the elderly needs to be better explored.
  
  
  OBJECTIVE
  To evaluate the effect of long-term lithium treatment at subtherapeutic doses on renal function in older adults. Secondary aims were to evaluate the clinical safety and tolerability of this treatment and its effects on thyroid, immune, and glycemic functions.
  
  
  METHODS
  Between February 2007 and October 2011, a 2-year randomized, double-blind, placebo-controlled trial followed by a single-blinded phase for an additional 2 years. Sixty-one patients with mild cognitive impairment (Mayo Clinic criteria) were randomized to receive lithium or placebo. Renal function was estimated by the abbreviated Modification of Diet in Renal Disease (aMDRD) and the Chronic Kidney Disease-Epidemiology study (CKD-EPI) equations. Leukocytes, serum thyroid-stimulating hormone (TSH) and free thyroxine (T₄), and serum glucose and insulin were determined. Tolerability was evaluated at 3-month intervals through systematic clinical examinations and by the UKU Side Effect Rating Scale.
  
  
  RESULTS
  Analysis of longitudinal regression indicated that no significant changes in renal function were detected by the aMDRD (P = .453) and CKD-EPI (P = .213) equations after 4 years of lithium treatment. Significant increases in the number of neutrophils (P = .038), serum TSH (P = .034), and body weight (P = .015) were observed in the lithium group. The lithium group presented more overall adverse events (P = .045), particularly interfering in daily activities (P < .001). In addition, those patients had a higher incidence of diabetes mellitus (P = .037) and arrhythmia (P = .028).
  
  
  CONCLUSIONS
  Chronic use of lithium at low doses did not affect renal function and was clinically safe. However, some other potentially relevant adverse events were observed and others could not be ruled out due to limitations of the study design.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01055392.
authors.forename: Ivan
authors.initials: I
authors.lastname: Aprahamian
authors.forename: Franklin S
authors.initials: FS
authors.lastname: Santos
authors.forename: Bernardo
authors.initials: B
authors.lastname: dos Santos
authors.forename: Leda
authors.initials: L
authors.lastname: Talib
authors.forename: Breno S
authors.initials: BS
authors.lastname: Diniz
authors.forename: Márcia
authors.initials: M
authors.lastname: Radanovic
authors.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: Department and Institute of Psychiatry, Laboratory of Neuroscience (LIM-27), Faculty of Medicine, University of São Paulo, Rua Dr Ovídio Pires de Campos 785, 05403-010-São Paulo, SP, Brazil forlenza@usp.br.
authors.forename: Orestes V
authors.initials: OV
authors.lastname: Forlenza
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D060825:Cognitive Dysfunction / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D008094:Lithium / Q000008:administration & dosage / Q000009:adverse effects*; D008134:Long-Term Care; D008137:Longitudinal Studies; D008297:Male; D010919:Placebos; D016037:Single-Blind Method; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D010919:Placebos; D008094:Lithium