Background: Depression is associated with increased cardiac morbidity and mortality in the general population and in patients with coronary heart disease (CHD). Recent evidence suggests that patients with new-onset depression post-CHD diagnosis have worse outcomes than do those who had previous or recurrent depression. This meta-analysis investigated the timing of depression onset in established CHD and CHD-free cohorts to determine what time frame is associated with greater mortality and cardiac morbidity.

Methodology/principal findings: The MEDLINE, EMBASE, and PsycINFO databases were searched systematically to identify articles examining a depression time frame that specified an end point of all-cause mortality, cardiac mortality, rehospitalization, or major adverse cardiac events. A meta-analysis was conducted to estimate effect sizes by time frame of depression. Twenty-two prospective cohort studies were identified. Nine studies investigated premorbid depression in CHD-free cohorts in relation to cardiac death. Thirteen studies in patient samples with CHD examined new-onset depression in comparison with previous or recurrent depression. The pooled effect size (risk ratio) was 0.76 (95% confidence interval (CI) = 0.48-1.19) for history of depression only, 1.79 (95% CI = 1.45-2.21) for premorbid depression onset, 2.11 (95% CI = 1.66-2.68) for postmorbid or new depression onset, and 1.59 (95% CI = 1.08-2.34) for recurrent depression.

Conclusions/significance: Both premorbid and postmorbid depression onsets are potentially hazardous, and the question of timing may be irrelevant with respect to adverse cardiac outcomes. However, the combination of premorbid depression with the absence of depression at the time of a cardiac event (i.e., historical depression only) is not associated with such outcomes and deserves further investigation.