Melatonin for Postoperative Pain

Recruiting in Palo Alto (17 mi)

Overseen by Jason Baker, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Montefiore Medical Center

Must not be taking: Melatonin, Psychotropic drugs

Disqualifiers: Substance abuse, Chronic pain, Psychiatric disease, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of the study is to assess if melatonin given for three nights before wisdom tooth surgery decreases post-operative pain and pain medication consumption. Patients will receive either melatonin or a placebo for three nights prior to surgery and we will measure pre-operative anxiety, preoperative sleep quality, post op pain medication consumption, post op pain scores, and blood values.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently taking melatonin or have a history of using psychotropic drugs (medications affecting the mind).

What data supports the effectiveness of the drug melatonin for reducing postoperative pain?

Research shows that melatonin can reduce postoperative pain severity, as seen in studies where patients undergoing surgeries like lumbar disc and colorectal surgeries experienced less pain when given melatonin compared to a placebo. Melatonin's analgesic (pain-relieving) effects are supported by its ability to reduce pain and anxiety, making it a potentially effective option for managing postoperative pain. ^{1 2 3 4 5}

Is melatonin safe for human use?

Melatonin is generally considered safe for human use, with studies showing it is well-tolerated in both children and adults for sleep-related issues. However, there is limited long-term safety data, and its effects during pregnancy or interactions with other medications are not fully understood. ^{6 7 8 9 10}

How does the drug melatonin differ from other treatments for postoperative pain?

Melatonin is unique for postoperative pain management because it is administered sublingually (under the tongue) before surgery, which can help reduce pain severity and anxiety after surgery. Unlike traditional pain medications, melatonin also has sedative and anti-inflammatory properties, making it a novel option for improving patient comfort and cooperation post-surgery. ^{1 4 11 12 13}

Research Team

Jason Baker, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

This trial is for healthy adults aged 18-35 needing wisdom tooth surgery under IV sedation, without allergies to melatonin or pain meds, no chronic pain or psychiatric conditions, not pregnant, and not currently using melatonin. They must be able to understand and sign the consent form.

Inclusion Criteria

ASA Class I or II

I speak English or Spanish.

I need 3-4 wisdom teeth removed with surgery under IV sedation.

Exclusion Criteria

You have a mental illness or difficulties with thinking.

Pregnancy

I have used or am using medication for mental health issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Preoperative Treatment

Participants receive either melatonin or placebo for three nights before surgery

1 week

No visits required

Surgery and Immediate Postoperative Monitoring

Participants undergo wisdom tooth surgery and immediate postoperative monitoring

1 day

1 visit (in-person)

Postoperative Follow-up

Participants complete surveys on pain and medication consumption for 5 days post-surgery

1 week

Surveys via text/email, 1 visit (in-person) on day 5

Follow-up

Participants are monitored for safety and effectiveness after treatment

2-4 weeks

Treatment Details

Interventions

• Lactose pill (Other)
• Melatonin (Hormone Therapy)

Trial Overview The study tests if taking melatonin for three nights before wisdom tooth removal can reduce post-surgery pain and need for painkillers. Participants will randomly receive either melatonin or a placebo pill (lactose) to compare effects on anxiety, sleep quality, post-op pain, medication use, and blood values.

Participant Groups

Group I: Experimental Treatment - Melatonin Experimental Treatment 1 Intervention

Premedication for three nights with 10mg melatonin

Group II: Control Treatment - Lactose Placebo Group 1 Intervention

Premedication for three nights with lactose capsules

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Andrew D. Racine

Montefiore Medical Center

Chief Medical Officer since 1992

MD, PhD from New York University; Undergraduate degree from Harvard University

Philip O. Ozuah

Montefiore Medical Center

Chief Executive Officer since 2019

MD, PhD from New York University

Findings from Research

Melatonin has shown significant analgesic and anxiolytic effects in surgical patients, with reductions of 20 mm and 19 mm on a pain scale compared to placebo, based on a systematic review of randomized studies.

However, a specific study using a human burn model found no significant analgesic effects of exogenous melatonin compared to placebo, indicating that while melatonin may be effective in some contexts, its efficacy in humans remains inconsistent and requires further high-quality research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The analgesic effects of exogenous melatonin in humans. Andersen, LP.[2022]

Ramelteon and agomelatine are melatonergic agonists that effectively improve sleep quality and duration in patients with insomnia and major depressive disorder, respectively, by targeting MT1 and MT2 receptors in the brain.

A slow-release formulation of melatonin, Circadin, has been shown to be effective for treating sleep disorders in the elderly, highlighting the importance of formulation in enhancing therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of melatonin agonists. Cardinali, DP., Pandi-Perumal, SR., Srinivasan, V., et al.[2019]

Melatonin can effectively improve sleep and adjust circadian rhythms when taken at the right times, helping with issues like jet lag and shift work, but its effectiveness is closely related to the timing and dosage.

While melatonin is generally safe for short-term use in healthy adults, there is a lack of long-term safety data, and its use should be carefully managed to avoid potential negative effects, especially with unregulated preparations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of circadian rhythm disorders--melatonin. Arendt, J., Deacon, S.[2019]

Circadian rhythm sleep-wake disorders (CRSWDs) affect millions and significantly impact quality of life, highlighting a critical need for effective treatments.

Melatonin receptor agonists, particularly tasimelteon, have shown promise in treating CRSWDs, with distinct pharmacologic profiles that may guide their clinical use, though further research is necessary to fully understand their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders. Williams, WP., McLin, DE., Dressman, MA., et al.[2022]

Melatonin is effective in reducing preoperative anxiety in adults, as shown in 9 out of 10 studies reviewed, making it a promising alternative premedicant.

The analgesic effects of melatonin are less clear, with mixed results in studies regarding its ability to reduce pain or opioid use during the perioperative period, indicating a need for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. Yousaf, F., Seet, E., Venkatraghavan, L., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Changes in Melatonin, Cortisol, and Body Temperature, and the Relationship Between Endogenous Melatonin Levels and Analgesia Consumption in Patients Undergoing Bariatric Surgery. [2019]

2. Ethiopia pubmed.ncbi.nlm.nih.gov

The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial. [2023]

3. Denmark pubmed.ncbi.nlm.nih.gov

The analgesic effects of exogenous melatonin in humans. [2022]

4. Iran pubmed.ncbi.nlm.nih.gov

The Effect of Preoperative Sublingual Melatonin on Postoperative Pain Severity in Patients Undergoing Colorectal Surgery: A Triple-Blinded Randomized Trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pineal opioid receptors and analgesic action of melatonin. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Therapeutic potential of melatonin agonists. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Treatment of circadian rhythm disorders--melatonin. [2019]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melatonin for sleep onset insomnia in children and adolescents: a meta-analysis of randomized controlled trials. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Comparative Review of Approved Melatonin Agonists for the Treatment of Circadian Rhythm Sleep-Wake Disorders. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Phase II double-blind randomised controlled trial of exogenous administration of melatonin in chronic pain (DREAM-CP): a study protocol. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. [2013]