ObjectiveTo examine the association between classes of antidepressants and hyponatremia, and between specific antidepressants and hyponatremia.DesignRetrospective register-based cohort study using nationwide registers from 1998 to 2012.SettingThe North Denmark Region.ParticipantsIn total, 638 352 individuals were included.Primary and secondary outcome measuresPlasma 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.ResultsAn 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).ConclusionsAll antidepressants except mianserin are associated with hyponatremia. The association is strongest with citalopram and lowest with duloxetine, venlafaxine and mirtazapine.

ObjectiveTo 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.DesignRetrospective nationwide cohort study.SettingDanish nationwide national registers.ParticipantsAll individuals in Denmark ≥65 years who used specified CVD-drugs in the study period between 1999 and 2012.Main outcomes measuresTime-dependent exposure to CVD-drugs (nitrates, digoxin, thiazides, furosemide, ACE inhibitors, angiotensin receptor antagonists, β-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.ResultsOverall, 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).ConclusionsUse 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.

In-hospital falls-related major injuries increased significantly during the study period. Elderly with dementia, osteoporosis, stroke, depression, chronic obstructive pulmonary disease and Parkinson disease were associated with increased OR for in-hospital fall-related major injuries. Increased focus on patients with these comorbidities is warranted to decrease the increasing incidence in in-hospital major injuries.

The results suggest that the overall reduction in fractures can be explained by reduction in falls related comorbidity.