Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials

BACKGROUND: Patients with nocturnal hypertension are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. Published studies inconsistently reported decreases in nocturnal blood pressure with melatonin. METHODS: A meta-analysis of the efficacy and safety of exogenous melatonin in ameliorating nocturnal blood pressure was performed using a random effects model of all studies fitting the inclusion criteria, with subgroup analysis of fast-release versus controlled-release preparations. RESULTS: Seven trials (three of controlled-release and four of fast-release melatonin) with 221 participants were included. Meta-analysis of all seven studies did not reveal significant effects of melatonin versus placebo on nocturnal blood pressure. However, subgroup analysis revealed that controlled-release melatonin significantly reduced nocturnal blood pressure whereas fast-release melatonin had no effect. Systolic blood pressure decreased significantly with controlled-release melatonin (−6.1 mmHg; 95% confidence interval [CI] −10.7 to −1.5; P = 0.009) but not fast-release melatonin (−0.3 mmHg; 95% CI −5.9 to 5.30; P = 0.92). Diastolic blood pressure also decreased significantly with controlled-release melatonin (−3.5 mmHg; 95% CI −6.1 to −0.9; P = 0.009) but not fast-release melatonin (−0.2 mmHg; 95% CI −3.8 to 3.3; P = 0.89). No safety concerns were raised. CONCLUSION: Add-on controlled-release melatonin to antihypertensive therapy is effective and safe in ameliorating nocturnal hypertension, whereas fast-release melatonin is ineffective. It is necessary that larger trials of longer duration be conducted in order to determine the long-term beneficial effects of controlled-release melatonin in patients with nocturnal hypertension.