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

TY - JOUR

T1 - Association of Psychotropic Prescriptions With Non-Registered Indications and the Risk of Mortality in Older Adults

T2 - A Danish Nationwide Cohort Study

AU - Ishtiak-Ahmed, Kazi

AU - Jensen-Dahm, Christina

AU - Christensen, Kaj Sparle

AU - Waldemar, Gunhild

AU - Gasse, Christiane

PY - 2024/11

Y1 - 2024/11

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Antidepressive Agents/therapeutic use

KW - Antipsychotic Agents/therapeutic use

KW - Benzodiazepines/therapeutic use

KW - Cohort Studies

KW - Dementia/drug therapy

KW - Denmark/epidemiology

KW - Drug Prescriptions/statistics & numerical data

KW - Female

KW - Humans

KW - Male

KW - Mental Disorders/drug therapy

KW - Mortality/trends

KW - Off-Label Use/statistics & numerical data

KW - Psychotropic Drugs/therapeutic use

KW - Registries

KW - benzodiazepines

KW - antidepressants

KW - off-label medication use

KW - antipsychotics

KW - dementia

UR - http://www.scopus.com/inward/record.url?scp=85209843810&partnerID=8YFLogxK

U2 - 10.1002/gps.70014

DO - 10.1002/gps.70014

M3 - Journal article

C2 - 39549021

SN - 0885-6230

VL - 39

JO - International Journal of Geriatric Psychiatry

JF - International Journal of Geriatric Psychiatry

IS - 11

M1 - e70014

ER -