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.

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.

METHOD: 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.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01055392.