Can melatonin induce hypotension, and what dosing and monitoring strategy should be used in a patient, particularly one taking antihypertensive medications?

Melatonin and Hypotension: Clinical Guidance

Melatonin can induce hypotension, particularly during nighttime hours, and this effect is most pronounced with controlled-release formulations at doses of 2-10 mg taken before bedtime. 1

Evidence for Hypotensive Effects

Melatonin's blood pressure-lowering properties are well-documented:

• Controlled-release melatonin (2 mg) significantly reduces nocturnal systolic blood pressure by approximately 6 mmHg and diastolic blood pressure by 3.5 mmHg in patients with nocturnal hypertension. 2

• Higher doses (10 mg) demonstrate similar hypotensive effects, reducing systolic blood pressure by approximately 4 mmHg and diastolic blood pressure by 2 mmHg during sleep. 3

• The hypotensive effect is most prominent between 2:00 AM and 5:00 AM. 4

• Critically, fast-release melatonin formulations do NOT produce significant blood pressure reductions, while controlled-release preparations consistently lower nocturnal blood pressure. 2

Dosing Strategy in Patients on Antihypertensives

For patients already taking antihypertensive medications:

• Start with controlled-release melatonin 2 mg taken 2 hours before bedtime, as this dose has been safely studied as add-on therapy to existing antihypertensive regimens. 4

• The American Academy of Sleep Medicine guidelines note that hypotension has been reported at higher melatonin doses in healthy adults, and the same effects occur at lower doses in patients with preexisting cardiovascular conditions. 1

• Doses up to 10 mg daily appear safe in healthy adults for short-term use, but caution is warranted in patients with preexisting hypotension or those on multiple antihypertensive agents. 1

Monitoring Strategy

Implement the following monitoring protocol:

• Obtain baseline 24-hour ambulatory blood pressure monitoring (ABPM) before initiating melatonin, particularly in patients taking antihypertensive medications. 4, 5

• Repeat ABPM after 3-4 weeks of melatonin therapy to assess nocturnal blood pressure response and ensure daytime blood pressure remains stable. 4, 5

• Monitor for symptoms of hypotension including dizziness, lightheadedness, or orthostatic symptoms, especially upon awakening or during nighttime bathroom trips. 1

• Key monitoring window: Focus on blood pressure measurements between 2:00 AM and 5:00 AM, when melatonin's hypotensive effect peaks. 4

Perioperative Considerations

Melatonin is safe to continue perioperatively:

• The Society for Perioperative Assessment and Quality Improvement recommends continuing melatonin through the perioperative period, as available evidence demonstrates safety and potential benefits for reducing preoperative anxiety and postoperative delirium. 1

• However, be aware that melatonin may increase the risk of intraoperative hypotension in patients taking multiple antihypertensive medications or vasodilators. 1

Common Pitfalls and Caveats

Avoid these critical errors:

• Do not assume all melatonin formulations have equivalent effects. Only controlled-release preparations consistently lower blood pressure; immediate-release products are ineffective for blood pressure reduction. 2

• Do not use melatonin in patients with symptomatic hypotension or those experiencing frequent orthostatic symptoms on their current antihypertensive regimen. 1

• Ensure patients use United States Pharmacopeial Convention Verified formulations, as melatonin is a dietary supplement with variable purity and dosing accuracy. 1

• Do not overlook drug interactions: Melatonin requires caution in patients taking warfarin, and NSAIDs, beta-blockers, and alcohol can suppress endogenous melatonin production. 1

Practical Implementation Algorithm

Follow this stepwise approach:

1. Assess baseline risk: Determine if patient has history of hypotension, orthostatic symptoms, or is taking multiple antihypertensive agents. 1

2. Choose appropriate formulation: Select controlled-release melatonin 2 mg if blood pressure lowering is acceptable or desired; avoid in patients requiring blood pressure stability. 2

3. Timing: Administer 2 hours before bedtime to maximize chronobiotic effects and align with natural melatonin secretion patterns. 4, 5

4. Initial monitoring: Check blood pressure within 1 week of initiation, focusing on morning readings to detect excessive nocturnal hypotension. 4

5. Definitive assessment: Obtain 24-hour ABPM at 3-4 weeks to quantify nocturnal blood pressure changes. 4, 5

6. Dose adjustment: If hypotension occurs, reduce to 1 mg or discontinue; if blood pressure remains elevated and nocturnal dipping is inadequate, consider increasing to 5-10 mg under close monitoring. 5, 3