The objective of this study is to explain inconsistencies in the relationship between depression and all-cause mortality by performing a reassessment of the included studies of previous systematic reviews. We assessed study-level methodological variables with a focus on sample size and follow-up period, measurement and classification of depression, and model adjustment. We included the constituent studies of fifteen systematic reviews on depression and mortality, yielding 488 articles after the

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... removal of duplicates. 333 studies were extracted, 40 of which used data that overlapped with other included studies. We included 313 estimates from 293 articles in the meta-analysis with a total sample of 3,604,005 participants and over 417,901 deaths. We identified a pronounced publication bias favoring large, positive associations in imprecise studies. Several factors moderated the relationship between depression and mortality. Most importantly, the 16 estimates adjusting for at least one comorbid mental condition (Pooled Effect: 1.08; 95% CI: 0.98-1.18), and the fraction of 8 of those estimates also adjusting for health variables (e.g., smoking, alcohol use, or physical inactivity; Pooled Effect: 1.04; 95% CI: 0.87-1.21), reported considerably smaller associations than the 204 unadjusted estimates (Pooled Effect: 1.32; 95% CI: 1.28-1.36). The sizable relationship of depression and mortality reported in previous systematic reviews is largely based on low-quality studies; controlling for important covariates attenuates the association considerably. Higher quality studies are needed based on large community samples, extensive follow-up, adjustment for health behaviors and mental disorders, and time-to-event outcomes based on survival analysis methodology.