Antidepressants and the risk of hyponatremia: a Danish register-based population study.

OBJECTIVE: To examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia. DESIGN: Retrospective register-based cohort study using nationwide registers from 1998 to 2012. SETTING: The North Denmark Region. PARTICIPANTS: In total, 638 352 individuals were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Plasma sodium was obtained from the LABKA database. The primary outcome was hyponatremia defined as plasma sodium (p-sodium) below 135 mmol/L and secondary outcome was severe hyponatremia defined as p-sodium below 130 mmol/L. The association between use of specific antidepressants and hyponatremia was analysed using multivariable Poisson regression models. RESULTS: An event of hyponatremia occurred in 72 509 individuals and 11.36% (n=6476) of these events happened during treatment with antidepressants. Incidence rate ratios and CIs for the association with hyponatremia in the first p-sodium measured after initiation of treatment were for citalopram 7.8 (CI 7.42 to 8.20); clomipramine 4.93 (CI 2.72 to 8.94); duloxetine 2.05 (CI 1.44 to 292); venlafaxine 2.90 (CI 2.43 to 3.46); mirtazapine 2.95 (CI 2.71 to 3.21); and mianserin 0.90 (CI 0.71 to 1.14). CONCLUSIONS: All antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.

Danish register-based study on the association between specific cardiovascular drugs and fragility fractures.

OBJECTIVE: To determine whether drugs used in treatment of cardiovascular diseases (CVD-drugs), including hypertension, increase the risk of fragility fractures in individuals above the age of 65 years. DESIGN: Retrospective nationwide cohort study. SETTING: Danish nationwide national registers. PARTICIPANTS: All individuals in Denmark ≥ 65 years who used specified CVD-drugs in the study period between 1999 and 2012. MAIN OUTCOMES MEASURES: Time-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, ß-blockers, calcium antagonists and statins) was determined by prescription claims from pharmacies. The association between use of specific CVD-drugs and fragility fractures was assessed using multivariable Poisson regression models, and adjusted incidence rate ratios (IRRs) were calculated. RESULTS: Overall, 1,586,554 persons were included, of these 16.1% experienced a fall-related fracture. The multivariable Poisson regression analysis showed positive associations between fracture and treatment with furosemide, thiazide and digoxin. IRRs during the first 14 days of treatment were for furosemide IRR 1.74 (95% CI 1.61 to 1.89) and for thiazides IRR 1.41 (1.28 to 1.55); IRR during the first 30 days of treatment with digoxin was 1.18 (1.02 to 1.37). CONCLUSIONS: Use of furosemide, thiazides and digoxin was associated with elevated rates of fragility fractures among elderly individuals. This may warrant consideration when considering diuretic treatment of hypertension in elderly individuals.

Falls and comorbidity: the pathway to fractures.

AIMS: To compare nationwide time trends and mortality in hip and proximal humeral fractures; to explore associations between incidences of falls risk related comorbidities (FRICs) and incidence of fractures. METHODS: The study is a retrospective cohort study using nationwide Danish administrative registries from 2000 through 2009. Individuals aged 65 years or older who experienced a hip or a proximal humeral fracture were included. Incidence of hip and of proximal humeral fractures, incidence of FRICs (ischemic heart disease, COPD, dementia, depression, diabetes, heart failure, osteoporosis, Parkinson's disease and stroke) and incidence rate ratios (IRR) for fractures in patients with FRICs, and all-cause mortality up to 10 years after a hip or a proximal humeral fracture were analysed. RESULTS: A total of 89,150 patients experienced hip fractures and 48,581 proximal humeral fractures. From 2000 through 2009, the incidence of hip fractures per 100,000 individuals declined by 198 (787 to 589, OR = 0.75, CI: 0.72-0.80) among males and by 483 (1758 to 1275, OR = 0.74, CI: 0.72-0.77) among females. Incidences of FRICs decreased. The absolute reduction in fractures was most pronounced for the age group above 75 years (2393 to 1884, OR = 0.81, CI: 0.78-0.83), but the relative reduction was more pronounced in the age group of 65-75 years old (496 to 342, OR = 0.70, CI: 0.66-0.74). IRRs for hip fractures and for proximal humeral fractures were significantly elevated in patients with FRICs. CONCLUSIONS: The results suggest that the overall reduction in fractures can be explained by reduction in falls related comorbidity.