The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons.

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11-2.16], p = .01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased ß1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.

Are higher antidepressant plasma concentrations associated with fall risk in older antidepressant users?

PURPOSE: Antidepressants are well-established fall-risk increasing drugs (FRIDs) and therefore falls should be considered an important adverse drug event (ADE) of antidepressants. However, not all antidepressant users experience fall incidents and factors associated with increased fall risk among antidepressant users are incompletely understood. Our objective was to explore whether antidepressant plasma concentrations are associated with falls in older antidepressant users. METHODS: For this study, we included antidepressant users of the multicenter B-PROOF study. Fall incidents were recorded prospectively using fall calendars. Antidepressant plasma concentrations were analyzed by Liquid chromatography-mass spectrometry (LC-MS) at baseline and at 2 years follow-up. The associations between the observed antidepressant concentration and fall risk were assessed using Cox proportional hazard and logistic regression models and adjusted for potential confounders. RESULTS: In total 93 selective serotonin reuptake inhibitor (SSRI) and 41 antidepressant (TCA) users were identified. There was a significant association between baseline TCA plasma concentration and fall risk within users (HR 2.50, 95% CI 1.07-5.87, crude model). In the adjusted model, there were no significant associations between concentrations of SSRIs and fall risk. CONCLUSION: There might be an association between plasma concentrations of TCAs and the risk of falling in older users. However, these results needs to be interpreted with caution considering the small sample size and accompanying limitation of confinement to crude analyses. Therefore, these novel findings need to replicated in a larger cohort, preferably including adjustment for potential confounders and more frequent measures of plasma concentrations is needed.

Depression, antidepressants and fall risk: therapeutic dilemmas-a clinical review.

PURPOSE: The aim of this clinical review was to summarize the existing knowledge on fall risk associated with antidepressant use in older adults, describe underlying mechanisms, and assist clinicians in decision-making with regard to (de-) prescribing antidepressants in older persons. METHODOLOGY: We comprehensively examined the literature based on a literature search in Pubmed and Google Scholar, and identified additional relevant articles from reference lists, with an emphasis on the most commonly prescribed drugs in depression in geriatric patients. We discuss use of antidepressants, potential fall-related side effects, and deprescribing of antidepressants in older persons. RESULTS: Untreated depression and antidepressant use both contribute to fall risk. Antidepressants are equally effective, but differ in fall-related side effect profile. They contribute to (or cause) falling through orthostatic hypotension, sedation/impaired attention, hyponatremia, movement disorder and cardiac toxicity. Falling is an important driver of morbidity and mortality and, therefore, requires prevention. If clinical condition allows, withdrawal of antidepressants is recommended in fall-prone elderly persons. An important barrier is reluctance of prescribers to deprescribe antidepressants resulting from fear of withdrawal symptoms or disease relapse/recurrence, and the level of complexity of deprescribing antidepressants in older persons with multiple comorbidities and medications. Practical resources and algorithms are available that guide and assist clinicians in deprescribing antidepressants. CONCLUSIONS: (De-) prescribing antidepressants in fall-prone older adults is often challenging, but detailed insight in fall-related side effect profile of the different antidepressants and a recently developed expert-based decision aid STOPPFalls assists prescribers in clinical decision-making.