Introduction
Falls in older adults are a major public health problem and associated
with substantial health care costs and decreased quality of life1. Annually, one-third of individuals over the age of
65 falls at least once and 20% of these falls lead to severe injuries2. Well established fall risk factors are
fall-risk-increasing drugs (FRIDs) 3 and
antidepressants use has consistently been associated with increased fall
risk 4. Therefore, falls should be considered a common
adverse drug event (ADE) of antidepressants 5.
However, not all antidepressant users fall and un(der)treated depression
also increases fall risk 6, 7. It is therefore
important to identify for whom the risk-benefit ratio of antidepressant
use is detrimental. Which individual factors in antidepressant users
contribute to fall risk, however, is not completely understood. A
dose-response relationship between antidepressants and the incidence of
falls has been demonstrated in older adults 8, 9.
However, in older adults there is substantial inter-individual variation
in drug pharmacokinetics and –dynamics 10, 11. Also,
often polypharmacy and multimorbidity are present, predisposing to high
prevalence of drug-drug and drug-disease interactions12. This makes predicting (adverse) drug effects based
on given dosage difficult. Therefore, the availability of antidepressant
plasma concentrations could be of value in predicting fall risk in
antidepressant users.
Measuring drug concentrations to guide dosing of medicines, optimize
treatment response and minimizing ADE, is called therapeutic drug
monitoring (TDM). Especially within psychiatry this is a widely used
approach 13. Whether antidepressant plasma
concentrations is associated with fall risk, however, has not been
studied before. Potentially antidepressant plasma concentration
measurements could guide clinical decision making in falls prevention.
For instance, with regard to decisions on deprescribing or exchanging
the antidepressant to a safer alternative. Therefore, our objective was
to explore whether fall risk in older adults is related to the
antidepressant concentration in plasma. We hypothesized that
antidepressant users with higher exposure in plasma would have a higher
risk of falling compared to those with lower concentrations.