The effect of melatonin on depressive symptoms and anxiety in patients after acute coronary syndrome: The MEDACIS randomized clinical trial

Depression following acute coronary syndrome is prevalent and associated with increased mortality and morbidity. Melatonin may function as a primary prophylactic antidepressant substance and alleviate depressive symptoms. The study was undertaken to determine if melatonin administered following an acute coronary syndrome (ACS) could prevent development of depression. The study was a double-blinded, placebo-controlled, multicenter, randomized clinical trial performed in five primary care cardiology departments at Zealand, Denmark. Included patients were adults patients, free of depression at baseline, included at the latest 4 weeks after acute coronary syndrome. Twenty-five mg melatonin or placebo was administered 1 h before participants’ bedtime for 12 weeks. The primary outcome is Major Depression Inventory (MDI) measured every two weeks throughout the trial. Incidence of depression was apriori defined as MDI score ≥ 21 during the trial. Reported exploratory outcomes were patterns of dropout and safety outcomes. 1220 patients were screened and 252 participants were randomized in a 1:1 ratio. Baseline MDI score in the melatonin and placebo group were, respectively, 6.18 (CI 5.32–7.05) and 5.98 (CI 5.19–6.77). No significant intergroup differences were found during the study in the intention-to-treat analysis or per-protocol analysis. Cumulative events of depressive episodes during the 12 weeks were six in the melatonin group and four in the placebo group. A significant drop in depressive symptoms were present throughout the study period. No intergroup differences were present in dropouts or adverse events. Melatonin showed no prophylactic antidepressant effect following acute coronary syndrome. The non-significant results might be due to a type II error or melatonin might not be able to prevent development of depressive symptoms following ACS.