TY - JOUR

T1 - Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression

T2 - A Nationwide Cohort Study in Denmark

AU - Ishtiak-Ahmed, Kazi

AU - Musliner, Katherine L

AU - Christensen, Kaj Sparle

AU - Mortensen, Erik Lykke

AU - Nierenberg, Andrew A

AU - Gasse, Christiane

PY - 2024

Y1 - 2024

N2 - OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years).CONCLUSIONS: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

AB - OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes.METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders.RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years).CONCLUSIONS: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

KW - Female

KW - Humans

KW - Aged

KW - Male

KW - Venlafaxine Hydrochloride

KW - Sertraline/therapeutic use

KW - Depression/drug therapy

KW - Cohort Studies

KW - Mirtazapine/therapeutic use

KW - Amitriptyline

KW - Antidepressive Agents/adverse effects

KW - Selective Serotonin Reuptake Inhibitors

KW - Cardiovascular Diseases

KW - Denmark/epidemiology

U2 - 10.1176/appi.ajp.20230356

DO - 10.1176/appi.ajp.20230356

M3 - Journal article

C2 - 37849303

VL - 181

SP - 47

EP - 56

JO - The American Journal of Psychiatry

JF - The American Journal of Psychiatry

SN - 0002-953X

IS - 1

ER -