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

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. 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. 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. 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.