ObjectivesTo evaluate the efficacy and safety of newer-generation antidepressants for patients with myocardial infarction (MI) and depression.MethodsPubMed, The Cochrane Library, EMbase, Web of Science, CBM, CNKI, WanFang Data, and VIP databases were searched from inception to December 2017 to collect randomized controlled trials (RCT) on newer-generation antidepressants for patients with MI and depression. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.3 software.ResultsTen RCTs involving 552 participants were included. The results showed that the antidepressant group was superior to the placebo or treatment group in terms of the improvement of depressive symptoms (SMD=–1.38, 95%CI –1.93 to –0.82, P<0.000 01), and incidence of angina (RR=0.42, 95%CI 0.25 to 0.71,P=0.001), recurrent MI (RR=0.43, 95%CI 0.22 to 0.83, P=0.01), and re-hospitalization for cardiac reasons (RR=0.51, 95%CI 0.28 to 0.92, P=0.03). However, there were no significant differences between two groups on all-cause mortality (RR=0.45, 95%CI 0.18 to 1.11, P=0.08), cardiovascular mortality (RR=0.53, 95%CI 0.16 to 1.73, P=0.29) and incidence of heart failure (RR=0.75, 95%CI 0.39 to 1.43, P=0.38). Subgroup analysis revealed that the type of antidepressants could affect the improvement of depression outcome. Citalopram and fluoxetine might be the most effective drugs for patients with MI and depression.ConclusionsNewer-generation antidepressants are effective for treatment of depressive symptoms in patients with MI and depression, with no significant impact on all-cause mortality and cardiovascular mortality. Moreover, antidepressants can reduce the incidence of angina, recurrent MI, and re-hospitalization for cardiac reasons in patients suffering from MI and depression. Due to limited quantity and quality of included studies, more high quality studies are required to verify above conclusions.