This study explores the bidirectional causal relationships between mental disorders, antidepressant use, and cardiovascular disease (CVD). Using Mendelian randomisation (MR) and multivariable MR (MVMR) analyses, the researchers evaluated potential causal links between 10 mental disorders, antidepressant use, and 7 CVDs. The findings indicate that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), and insomnia are associated with an increased risk of multiple CVDs. Antidepressant use is linked to an increased risk of each CVD, while each CVD is associated with a higher probability of antidepressant use. The MVMR analysis showed that antidepressant use is correlated with elevated risks across all cardiovascular conditions, including arrhythmias, atrial fibrillation, coronary artery disease, hypertension, heart failure, stroke, and the overall CVD group. However, MDD itself was not linked to a heightened risk of any CVD. The study highlights the use of antidepressants as an independent risk factor for CVD, explaining the influence of MDD on CVD through the mediating effects of antidepressants. Clinical implications suggest that when treating patients with antidepressants, the potential beneficial and detrimental effects should be considered. The study also found that CVD has minimal causal effects on mental disorders, with only hypertension showing a slight increased risk of ADHD and MDD. The results suggest that MDD, insomnia, and ADHD are robustly associated with an increased risk of CVD, with MDD being the leading contributor. The study underscores the complex interplay between mental disorders, antidepressant use, and CVD, emphasizing the need for careful consideration of antidepressant use in patients with CVD.This study explores the bidirectional causal relationships between mental disorders, antidepressant use, and cardiovascular disease (CVD). Using Mendelian randomisation (MR) and multivariable MR (MVMR) analyses, the researchers evaluated potential causal links between 10 mental disorders, antidepressant use, and 7 CVDs. The findings indicate that major depressive disorder (MDD), attention-deficit/hyperactivity disorder (ADHD), and insomnia are associated with an increased risk of multiple CVDs. Antidepressant use is linked to an increased risk of each CVD, while each CVD is associated with a higher probability of antidepressant use. The MVMR analysis showed that antidepressant use is correlated with elevated risks across all cardiovascular conditions, including arrhythmias, atrial fibrillation, coronary artery disease, hypertension, heart failure, stroke, and the overall CVD group. However, MDD itself was not linked to a heightened risk of any CVD. The study highlights the use of antidepressants as an independent risk factor for CVD, explaining the influence of MDD on CVD through the mediating effects of antidepressants. Clinical implications suggest that when treating patients with antidepressants, the potential beneficial and detrimental effects should be considered. The study also found that CVD has minimal causal effects on mental disorders, with only hypertension showing a slight increased risk of ADHD and MDD. The results suggest that MDD, insomnia, and ADHD are robustly associated with an increased risk of CVD, with MDD being the leading contributor. The study underscores the complex interplay between mental disorders, antidepressant use, and CVD, emphasizing the need for careful consideration of antidepressant use in patients with CVD.