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Zivin K, Kim HM, Yosef M, Maust DT, Valenstein M, Smith EG, Davydow DS. Antidepressant Medication Treatment and Risk of Death. Journal of Clinical Psychopharmacology. 2016 Oct 1; 36(5):445-52.
OBJECTIVE: Although previous studies have assessed whether depression is a mortality risk factor, few have examined whether antidepressant medications (ADMs) influence mortality risk. METHODS: We estimated hazards of 1-year all-cause mortality associated with ADMs, with use occurring within 90 days of depression diagnosis among 720 821 patients who received treatment in a Veterans Health Administration facility during fiscal year 2006. We addressed treatment selection biases using conventional Cox regression, propensity-stratified Cox regression (propensity score), and 2 forms of marginal structural models. Models accounted for multiple potential clinical and demographic confounders, and sensitivity analyses compared findings by antidepressant class. RESULTS: Antidepressant medication use compared with no use was associated with significantly lower hazards of 1-year mortality risk in Cox (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.90-0.97) and propensity score estimates (HR, 0.94; 95% CI, 0.91-0.98), whereas marginal structural model-based estimates showed no difference in mortality risk when the exposure was specified as "as-treated" in every 90-day intervals of the 1-year follow-up (HR, 0.91; 95% CI, 0.66-1.26) but showed increased risk when specified as "intent-to-treat" (HR, 1.07; 95% CI, 1.02-1.13). CONCLUSIONS: Among patients treated with ADMs belonging to a single class in the first 90 days, there were no significant differences in 1-year all-cause mortality risks. When accounting for clinical and demographic characteristics and treatment selection bias, ADM use was associated with no excess harm.