What is the clinical evidence from this study?

Study design: Cohort. Population: General population (n=222121). Intervention: Antidepressant use (SSRIs and other classes) vs. No antidepressant use. Primary outcome: All-cause mortality at 10 years (SSRI treatment) (HR 1.73, 95% CI 1.48-2.03).

September 1, 2022Open Access

Antidepressant use and risk of adverse outcomes: population-based cohort study

Resultado clave

At 10-year follow-up, SSRI treatment was associated with an increased risk of all-cause mortality (HR 1.73) and cardiovascular mortality (HR 1.87) compared to no antidepressant use.

Diseño del estudio

Tipo

Cohort (n=222,121)

Multicéntrico

Sí

PICO estructurado

Does long-term antidepressant use increase the risk of cardiometabolic morbidity and mortality in a general adult population?

Población

222,121 UK Biobank participants aged 40-69 years, free of prior antidepressant prescriptions or outcomes of interest at baseline, followed for up to 10 years.

Exposición

Antidepressant use (time-varying exposure), categorized by drug class as selective serotonin reuptake inhibitors (SSRIs: citalopram, sertraline, fluoxetine, paroxetine) and 'other' antidepressants (mirtazapine, venlafaxine, duloxetine, trazodone).

Comparador

No antidepressant use (unexposed time periods before starting treatment and unexposed time for those who did not receive an antidepressant prescription during follow-up).

Resultado

Four morbidity outcomes (diabetes, hypertension, coronary heart disease [CHD], cerebrovascular disease [CV]) and two mortality outcomes (cardiovascular disease [CVD] mortality and all-cause mortality) at 5- and 10-year follow-up.hard clinical

Long-term antidepressant use, particularly non-SSRI classes, is associated with significantly elevated risks of coronary heart disease, cardiovascular mortality, and all-cause mortality, highlighting the need for careful cardiovascular risk assessment in these patients.

Resultado numérico

Hazard Ratio: 1.73 (95% CI 1.48–2.03)

Limitaciones

Time lag between measurement of confounders and outcomes (up to 5 and 10 years)
Possibility of residual confounding
Low number of events prevented comparison by individual antidepressants
No information on the severity of depression at the time of prescription and outcome
No information on dosing schedule
Potential misclassification of exposure due to non-adherence
Study cohort is mostly of White British ethnic origin

Resumen

BACKGROUND: Antidepressants are one of the most widely prescribed drugs in the global north. However, little is known about the health consequences of long-term treatment. AIMS: This study aimed to investigate the association between antidepressant use and adverse events. METHOD: = 222 121). We assessed the association between antidepressant use by drug class (selective serotonin reuptake inhibitors (SSRIs) and 'other') and four morbidity (diabetes, hypertension, coronary heart disease (CHD), cerebrovascular disease (CV)) and two mortality (cardiovascular disease (CVD) and all-cause) outcomes, using Cox's proportional hazards model at 5- and 10-year follow-up. RESULTS: SSRI treatment was associated with decreased risk of diabetes at 5 years (hazard ratio 0.64, 95% CI 0.49-0.83) and 10 years (hazard ratio 0.68, 95% CI 0.53-0.87), and hypertension at 10 years (hazard ratio 0.77, 95% CI 0.66-0.89). At 10-year follow-up, SSRI treatment was associated with increased risks of CV (hazard ratio 1.34, 95% CI 1.02-1.77), CVD mortality (hazard ratio 1.87, 95% CI 1.38-2.53) and all-cause mortality (hazard ratio 1.73, 95% CI 1.48-2.03), and 'other' class treatment was associated with increased risk of CHD (hazard ratio 1.99, 95% CI 1.31-3.01), CVD (hazard ratio 1.86, 95% CI 1.10-3.15) and all-cause mortality (hazard ratio 2.20, 95% CI 1.71-2.84). CONCLUSIONS: Our findings indicate an association between long-term antidepressant usage and elevated risks of CHD, CVD mortality and all-cause mortality. Further research is needed to assess whether the observed associations are causal, and elucidate the underlying mechanisms.

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