Age as a determinant of instability of serum lithium concentrations.

BACKGROUND: Lithium is used both in bipolar disorder and as augmentation in treatment-resistant unipolar depression. Long-term treatment is often indicated. Pharmacokinetic and pharmacodynamic changes in older age, as well as increasing comorbidities and polypharmacy, could result in instability of serum lithium concentrations. In this study, several parameters, considered proxy for instability, were compared between age groups. These parameters were derived from studies involving oral anticoagulants. METHODS: A retrospective study (1995-2004) was conducted using serum lithium concentrations from the laboratories of 3 hospitals in the Netherlands; 759 patients treated with lithium, 40 years or older, with at least 2 years' follow-up were identified. They were divided into 4 age groups: 40-49, 50-59, 60-69, and 70+ years; the youngest group was used as a reference group. The variance growth rate and percentage of time below, in, and above treatment range are all proxies for instability. They were analyzed between the age categories. RESULTS: There was no significant difference for these variables between the reference group and the older age groups. In a subgroup of 454 patients, the parameters considered as proxy for instability during titration, number of days and number of serum lithium concentration measurements during titration, were evaluated; no significant difference was found between the age groups. In a small group of 117 patients, titration and maintenance treatment for at least 2 years could be analyzed separately. Also in this group, there was no difference between the age groups. CONCLUSIONS: Age is not a determinant of serum lithium concentration instability. Therefore, age is not a reason to not initiate or discontinue lithium therapy.

Renal effects of long-term lithium therapy in the elderly: a cross-sectional study.

OBJECTIVES: To determine the effect of long-term lithium therapy on glomerular filtration rate (GFR) and maximum renal concentrating capacity (Umax) in the elderly, to identify possible risk factors, to determine the clinical impact of a reduced Umax in this population and in case of polyuria to establish a diagnosis. METHODS: This is a cross-sectional study with 48 outpatients of 65 years or over (mean 74.8 years), who were treated with lithium for more than 6 months (mean 9.2 years). The GFR was determined with the Cockcroft-Gault formula (GFR-CG) and the Umax was measured in a urine sample collected between 3 and 5 h after the patients received 40 microg desmopressin (DDAVP) intranasally. RESULTS: No relation was found between duration of lithium treatment and GFR-CG, but there was a significant negative relation between duration of lithium treatment and Umax (B -0.73; CI: -1.249/-0.212); 73% of the patients had a moderate to severe concentrating defect. No other risk factors than duration of lithium therapy were identified. A reduced Umax caused polyuria (>2500 mL/24 h) in 33% but did not cause significant more thirst, incontinence or disturbed sleep. CONCLUSIONS: In this geriatric population a negative relation was found between duration of lithium treatment and Umax. But a reduced Umax did not result in significant more clinical symptoms. In case of polyuria other mechanisms beside nephrogenic diabetes insipidus were found to play a role in this age group.