Melatonin for Postoperative Pain

Recruiting at 1 trial location

Overseen By Charles K Levin, DDS

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Montefiore Medical Center

Must not be taking: Melatonin, Psychotropic drugs

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether taking melatonin before wisdom tooth surgery can reduce pain and the need for pain medications afterward. Participants will receive either melatonin or a placebo (a lactose pill with no active ingredients) for three nights before their surgery. The trial examines anxiety and sleep quality before surgery, as well as pain and medication use afterward. This study may suit individuals needing surgical removal of impacted wisdom teeth under IV sedation, provided they have no allergies to melatonin or a history of chronic pain. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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).

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that melatonin is generally safe for short-term use in people. Studies have found that taking melatonin before surgery can reduce postoperative pain without causing serious side effects. For instance, one study found that 5 mg of melatonin lowered pain after surgery without severe problems. Even higher doses have been used safely around surgery time without major issues.

However, melatonin's effects can vary, and information about its long-term safety remains limited. For short-term use, such as in this trial, melatonin is considered well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard pain relief options for postoperative pain, which often include opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), melatonin offers a unique approach. Melatonin, a hormone naturally found in the body, is being explored for its potential to reduce pain and improve sleep without the risk of addiction or significant side effects. Researchers are particularly excited about melatonin because it might provide pain relief by modulating sleep patterns and reducing anxiety, which can be particularly beneficial in the recovery process after surgery. By targeting these areas, melatonin could offer a safer, more holistic alternative to traditional pain management strategies.

What evidence suggests that melatonin might be an effective treatment for postoperative pain?

Studies have shown that melatonin might reduce pain and the need for pain medications after surgery. For example, research on jaw surgery found that melatonin aided pain relief and reduced opioid use. Another study compared melatonin with other treatments and found it helped with pain and anxiety after back surgery. However, other research has shown mixed results on melatonin's benefits for sleep and pain after surgery. In this trial, participants will receive either melatonin or a lactose placebo to evaluate its effectiveness in managing postoperative pain. Overall, melatonin appears promising, but its full effectiveness remains under study. ^{6 7 8 9 10}

Who Is on the Research Team?

Jason Baker, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

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

I am able to understand and sign the consent form.

Exclusion Criteria

You have a mental illness or difficulties with thinking.

Pregnancy

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Lactose pill
• Melatonin

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.

How Is the Trial Designed?

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+

Quest Diagnostics-Nichols Insitute

Industry Sponsor

Trials

14

Recruited

26,500+

Eurofins Viracor

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

A systematic review of six randomized clinical trials involving children aged 2 to 18 with autism spectrum disorder (ASD) and/or attention-deficit hyperactivity disorder (ADHD) found that melatonin significantly improved sleep duration and reduced sleep onset latency compared to placebo.

Melatonin is considered safe and well-tolerated in children and adolescents at doses ranging from 2 to 10 mg per day, making it a viable option for treating sleep problems in this population.

NCBI (Pubmed)

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. Parvataneni, T., Srinivas, S., Shah, K., et al.[2020]

In a study involving 80 patients undergoing lumbar disc surgery, preoperative oral melatonin significantly reduced postoperative pain compared to a placebo, particularly at a dose of 5 mg.

The use of 5 mg melatonin not only lowered pain intensity but also decreased the amount of opioids needed post-surgery, with no serious side effects reported, making it a safe and cost-effective option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Preoperative Oral Melatonin on Postoperative Pain after Lumbar Disc Surgery: A Double-Blinded Randomized Clinical Trial. Baradari, AG., Habibi, MR., Aarabi, M., et al.[2023]

Melatonin has natural analgesic properties that are most effective at night, aligning with its circadian rhythm, which could explain why patients report less pain and need fewer painkillers during nighttime.

Future research may focus on developing melatonin analogues that enhance pain relief without the addiction risks associated with traditional opioids, potentially offering a safer alternative for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pineal opioid receptors and analgesic action of melatonin. Ebadi, M., Govitrapong, P., Phansuwan-Pujito, P., et al.[2019]

In a study of 60 patients undergoing colorectal surgery, preoperative administration of 6 mg sublingual melatonin significantly reduced postoperative pain severity compared to a placebo, particularly at 2, 6, 12, and 24 hours after surgery.

Patients receiving melatonin also exhibited higher levels of cooperation and calmness post-surgery, suggesting that melatonin not only alleviates pain but may also help reduce anxiety and improve overall patient experience.

NCBI (Pubmed)

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. SaberMoghaddam, M., Sheybani, S., Bakhtiari, E., et al.[2022]

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]

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 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]

Melatonin has demonstrated significant analgesic effects in both experimental and clinical studies, particularly benefiting patients with chronic pain conditions such as fibromyalgia, irritable bowel syndrome, and migraines.

The exact mechanism of melatonin's analgesic action remains unclear, but it may involve interactions with specific receptors (like G(i)-coupled melatonin and opioid μ-receptors) and could also be linked to its ability to improve sleep and reduce anxiety, which in turn may lower pain levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analgesic effects of melatonin: a review of current evidence from experimental and clinical studies. Wilhelmsen, M., Amirian, I., Reiter, RJ., et al.[2013]

In a study of 30 patients undergoing laparoscopic bariatric surgery, endogenous melatonin levels significantly decreased during and after surgery, which may impact pain management.

There was a significant inverse correlation between lower melatonin levels and higher postoperative morphine consumption, suggesting that melatonin may play a role in analgesic requirements after surgery.

NCBI (Pubmed)

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. Altunkaya, N., Erdogan, MA., Ozgul, U., 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]

Melatonin significantly reduced sleep onset time (SOT) by an average of 0.62 hours and improved dim light melatonin onset (DLMO) by 0.82 hours in children and adolescents with sleep onset insomnia, based on a review of seven trials involving 387 participants.

The treatment was found to be effective and generally well-tolerated, with no significant differences in dropout rates due to adverse events, although some mild adverse effects were reported, indicating a need for further research, especially in adolescents.

NCBI (Pubmed)

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. Wei, S., Smits, MG., Tang, X., et al.[2022]

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]

This study will investigate the effects of 2 mg of oral melatonin (Circadin) on sleep disturbance and pain intensity in 60 adults with severe chronic pain lasting at least 3 months, using a randomized double-blind placebo-controlled cross-over design over 20 weeks.

The primary outcome is sleep disturbance, while secondary outcomes include pain intensity and various sleep measures, allowing for a comprehensive assessment of melatonin's potential analgesic and sleep-improving effects.

NCBI (Pubmed)

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. Adam, R., Kanakarajan, S., Onyeakazi, U., et al.[2021]

Citations

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The impact of postoperative pain interventions on circadian ... Recent studies have shown that postoperative pain not only affects the physiological state of patients but may also disrupt their circadian rhythms.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0020138322007811

Effectiveness of melatonin treatment for sleep disturbance ... Recent studies have demonstrated that postoperative melatonin administration has beneficial effects on pain and opioid use in orthognathic surgery[15] ...

3. bmcanesthesiol.biomedcentral.com bmcanesthesiol.biomedcentral.com/articles/10.1186/s12871-022-01851-x

Comparison of the effect of melatonin, dexmedetomidine, and ... This study aimed to compare the effects of melatonin, dexmedetomidine, and gabapentin on postoperative pain and anxiety following laminectomy.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01505465

Study of Melatonin on Sleep, Pain, and Confusion After ... Previous studies have found conflicting results regarding the potential for melatonin to improve sleep and pain in the perioperative period [14] .

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9519126/

Effects of Melatonin Treatment on Perioperative Sleep Quality Melatonin treatment can improve postoperative sleep quality. A 6mg daily dose of melatonin may have a better beneficial effect, which needs further exploration.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9692143/

The Effect of Preoperative Oral Melatonin on Postoperative ... It seems that the use of melatonin at a dose of 5 mg before the surgery is an effective and safe option for reduction of postoperative pain intensity, amount of ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11089947/

Efficacy and safety of perioperative melatonin for ... In our study, the perioperative use of melatonin and melatonin agonists decreased POD without severe adverse events, particularly at higher ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06724432

Analgesic and Antioxidant Effects of Melatonin in Pediatric ... We tested the hypothesis that melatonin reduces postoperative pain and oxidative stress involving sirtuin pathway in children undergoing surgery.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2049080121002958

Effects of preoperative melatonin on postoperative pain ... The mean pain intensity after surgery in patients receiving 5 mg melatonin was significantly lower than in the placebo group and in patients receiving 10 mg ...

10. withpower.com withpower.com/trial/melatonin-for-postoperative-pain-0ecdf

Melatonin for Postoperative Pain · Info for Participants Melatonin is generally considered safe for short-term use in humans, with low toxicity reported in studies. However, there is a lack of long-term safety data, ...