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.