Tolerability of lithium: A naturalistic discontinuation study in older inpatients (≥60 years).

OBJECTIVES: Lithium is one of the most effective treatment options in both bipolar disorder and treatment-resistant depression. The use of lithium in older patients declined during the last decades, probably resulting in undertreatment of older patients. To investigate how well lithium is tolerated in old age, we aimed to determine the frequency, reasons, and possible predictors of discontinuation due to adverse effects in a cohort of inpatients ≥60 years who had started with lithium. METHODS: We performed a retrospective cohort study based on chart reviews. Participants were in treatment at Parnassia Group at The Hague, The Netherlands. After inclusion (between January 2010 and December 2016), participants were followed until April 2017, when we performed data extraction and analysis. RESULTS: In our sample of 135 patients (median age 69 years, median follow-up duration 18 months), 49 (36.3%) participants discontinued lithium. Only a minority (11 [8.1%]) of the participants discontinued solely due to adverse effects. The majority discontinued lithium due to psychiatric (18, 5%) reasons (most commonly mentioned within this subgroup: lack of effectiveness and noncompliance) or a combination of reasons (7.4%). None of the factors we studied (age, gender, Charlson Comorbidity Index, polypharmacy, renal function, and neurological history) were significantly associated with discontinuation due to adverse effects. CONCLUSIONS: The frequency of lithium discontinuation in our cohort was in range with frequencies reported in younger patients. Older age itself should not be a reason to withhold lithium treatment.

The influence of lithium on calcium homeostasis in older patients in daily clinical practice.

BACKGROUND: Lithium can influence calcium homeostasis resulting in changes in parathormone set point and renal calcium handling. The clinical significance of these changes in older patients is unknown. The objective of this study was to investigate the possible association between duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion in older psychiatric patients corrected for renal function and vitamin 25OH D and also to estimate the point prevalence of hypercalcemia and raised parathormone. METHODS: A cross-sectional study of psychiatric outpatients visiting a specialized facility for older patients treated with lithium was performed. Patients underwent a comprehensive assessment and blood and urine testing. Potential confounders of calcium homeostasis were recorded. On the basis of the duration of lithium treatment, patients were divided into four groups. RESULTS: One hundred eleven patients were included, mean age 75.2 years. There was no significant association between the duration of lithium treatment and corrected calcium, parathormone and 24-h urinary calcium excretion. The point prevalence of hypercalcemia was 2.7% and 47.8% for raised parathormone. There was an unexpected but significant negative association between the duration of lithium treatment and vitamin 25OH D, with 76.9% vitamin 25OH D deficiency (<50 nmol/L) in the group using lithium for more than 10 years. CONCLUSIONS: No association was found between duration of lithium treatment and calcium parameters in older psychiatric outpatients, but there was a high prevalence of raised parathormone and an unexpected negative association between duration of lithium treatment and 25OH D.

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.

Prevalence and determinants of thyroid disorders in elderly patients with affective disorders: lithium and nonlithium patients.

OBJECTIVES: To determine the prevalence and determinants of thyroid dysfunction in older patients with affective disorders divided into lithium and nonlithium patients. METHODS: This study was conducted as a retrospective cross-sectional study in patients of 65 years and older with affective disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The presence of thyroid disorders was determined on the index date defined as the date of the first available thyroid-stimulating hormone in 2005. The presence of thyroid disorder was diagnosed according to defined criteria and in case of a previous diagnosis, confirmed by researching the medical files. In a subgroup of 45 lithium patients, thyroperoxidase- and thyroglobulin antibodies were determined. RESULTS: A total of 79 lithium patients and 85 nonlithium patients were included. The prevalence of hypothyroidism (subclinical and clinical) was 35.4% among the lithium patients, with women having a prevalence as high as 41.3% and men 12.6%. In the nonlithium patients, the prevalence was 7.1%; very close to that in the general population. No other determinant than female gender was identified. Seventeen of the 26 lithium patients were diagnosed with hypothyroidism in the first 31/2 years after the start of lithium. The prevalence of thyroid antibodies was 27% in 45 lithium patients, which was no different than the prevalence in the same age group in the general population. CONCLUSION: The prevalence of hypothyroidism during lithium treatment was very high in the elderly, especially in women. Autoimmunity did not seem to play a major part in lithium-associated hypothyroidism in this age group. The timeframe between start of lithium and diagnosis of hypothyroidism suggests an individual susceptibility. The prevalence of hypothyroidism in nonlithium patients with affective disorders was not very different from the general population.

Differences in lithium use patterns in the Netherlands: comparing middle-aged and older patients in a database study.

BACKGROUND: Age-dependent changes in lithium pharmacokinetic and pharmacodynamic properties can influence lithium use in an aging population, especially as newer treatment options are available. OBJECTIVE: We compared lithium use patterns between middle-aged and elderly outpatients in the Netherlands. METHODS: Data for this study were obtained from the Dutch PHARMO Record Linkage System. Incident lithium users 40 years or older were identified in the period 1996-2008. The following lithium use patterns were defined: continuation, add on, switch, and discontinuation. Differences were assessed for the following age groups: 40 to 49 years, 50 to 59 years, 60 to 69 years, and 70 years or older. The youngest group was the reference group. Patient baseline characteristics and potential determinants of changes in lithium use patterns were assessed. RESULTS: We identified 2081 incident lithium users. Use of antidepressants was not different at baseline between age groups, but elderly patients starting lithium treatment used baseline antipsychotics less frequently (P < 0.05). Older patients were less likely to receive psychotropic drugs as add on to ongoing lithium therapy (P < 0.05). Frequency of discontinuation and switch events did not differ between the age groups. In the whole study group, age was associated with any change in lithium use patterns. CONCLUSIONS: Older patients are less likely to receive psychotropic drugs as add on to ongoing lithium therapy. Despite pharmacokinetic and pharmacodynamic changes in the elderly, lithium is not more often discontinued and not more often switched in older patients.

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.