Association of Psychotropic Prescriptions With Non-Registered Indications and the Risk of Mortality in Older Adults: A Danish Nationwide Cohort Study

BACKGROUND AND OBJECTIVE: Psychotropic drug use is common in older adults, with off-label use reported despite limited understanding of the safety outcomes compared to on-label use. Incomplete recordings of treatment indications in the Danish National Prescription Register (DNPR) raise concerns about potential off-label medication use, particularly among older adults. We, therefore, investigated the association between psychotropic prescriptions with non-registered indications in DNPR and the 1-year all-cause mortality in older adults, including subgroups with any psychiatric disorders, depression, or dementia.

METHODS: Register-based cohort study following all older adults (≥ 65) who redeemed a first-time (since 1995) prescription of either antidepressants, antipsychotics, or benzodiazepine during 2006-2017. Redemption of a prescription with non-registered indications in the DNPR was the exposure. The outcome, 1-year all-cause mortality was analyzed using Poisson regression, estimating incidence rate ratios with 95% confidence intervals, adjusting for socio-demographics and clinical factors.

RESULTS: 32% of prescriptions filled by 202,067 individuals for antidepressants, 37% of 97,387 for antipsychotics, and 22% of 130,471 for benzodiazepines had non-registered indications. No significant differences in mortality rates were found for antidepressants and antipsychotics with non-registered indications, while higher mortality rates were associated with benzodiazepines, mitigated when excluding individuals receiving intravenous administrations representing end-of-life treatment. The results remained consistent in subgroup analyses in patients with any psychiatric disorders, depression, or dementia and further stratified analyses by sex and age.

CONCLUSIONS: We found that while psychotropic prescriptions with non-registered indications in DNPR were prevalent in older adults, they were not associated with excess mortality.