Lithium in older patients: treatment patterns and somatic adverse effects

Abstract

Lithium has been used in psychiatry for over 60 years and is still one of the first-line treatments in bipolar disorder. It is also used as augmentation to antidepressants in treatment resistant depression. Age-dependent changes in lithium pharmacokinetics and pharmacodynamics may influence lithium use patterns in an ageing population. Multimorbidity and polypharmacy could make older patients more vulnerable to the adverse effects of lithium. The main objectives of this thesis were to study the treatment patterns and the occurrence of somatic adverse effects of lithium and their possible determinants in older patients. We compared lithium use patterns between middle-aged and elderly outpatients in the Netherlands. Older patients were less likely to receive add-on of psychopharmacologic drugs next to ongoing lithium therapy and lithium was not more often discontinued and not more often switched in older than in middle-aged patients. A case description with lithium intoxication illustrated the importance of monitoring and of recognising (prodromal) symptoms of intoxication. A retrospective study was conducted to ascertain if age was a determinant of instability of the serum lithium concentration (SLC) using SLC from the laboratories of three hospitals in the Netherlands. In this study age was not found to be a determinant of SLC instability. To determine the effect of long-term lithium therapy on glomerular filtration rate (GFR) and maximum renal concentrating capacity (Umax) in the elderly, we conducted a cross-sectional study with 48 outpatients of 65 years or over. No association was found between duration of lithium use and estimated GFR, but there was a significant association between duration of lithium treatment and decrease in Umax. No other risk factors than duration of lithium therapy were identified. A reduced Umax did not cause significant more thirst, incontinence or disturbed sleep. In a cross-sectional study, we ascertained the prevalence of known cardiovascular risk factors (CVR) and the prevalence of cardiovascular disease (CVD) in elderly patients treated with lithium. There was a lower prevalence of hyperlipidemia compared with two population studies. The prevalence of ischemic heart disease was lower and the prevalence of cerebrovascular disease was higher in our study than in the general population. There was no association with duration of lithium use and CVR and CVD except for an increase in BMI in the first years of lithium use. To determine the prevalence and determinants of thyroid dysfunction in older patients with an affective disorder a retrospective cross-sectional study was conducted in patients of 65 years and older; 79 lithium patients and 85 nonlithium patients were included. The prevalence of hypothyroidism was 35.4% among the lithium patients and 7.1% in the nonlithium patients; this was very close to the prevalence in the general population. Female gender was the only determinant for the presence of thyroid disorder. Seventeen out of 26 lithium patients with hypothyroidism were diagnosed in the first three and a half years after lithium initiation. We found no association between duration of lithium treatment and calcium parameters in a cross-sectional study in elderly psychiatric outpatients. There was a high prevalence of raised parathormone (49%), perhaps partly because of a high prevalence of vitamin 25OH D deficiency (56.4% <50 nmol/L). There was an unexpected association between duration of lithium treatment and decrease in vitamin 25OH D. We state that a specialized lithium ambulatory clinic for the elderly could improve the quality of care for the older psychiatric patient. Lithium treatment in the elderly can be safe, if the patient is adequately monitored.