Are higher antidepressant plasma concentrations associated with fall
risk in older antidepressant users?
Aim 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, or concentration change over time (delta) 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). Adjusted there were no significant
associations between concentrations of SSRIs and fall risk. Also, for
delta concentrations there was no association with fall risk in users.
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,
replication in a larger cohort, preferably including adjustment for
potential confounders and more frequent measures of plasma
concentrations is needed.