Melatonin Lotion for Sleep Disorders

Overseen By Steven Moore, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Redlands

Must not be taking: Antidepressants, Anti-anxiety, Sleep meds

Disqualifiers: Pregnancy, Lotion allergies, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to examine the effect that melatonin lotion has on sleep quality, the nervous system, and mental health. Melatonin is a hormone secreted by the brain that regulates sleep and might improve depression and anxiety symptoms. The goal is to determine whether melatonin in lotion form is an effective treatment for young adults with inadequate sleep and might improve mental health. Participants will fill out surveys, wear an actigraph (a wrist-worn device that measures sleep), wear a heart rate monitor (a strap worn around one's chest), and provide nightly saliva samples during treatment weeks. In one of the two treatment weeks, participants will receive a lotion that contains melatonin. During the other week they will receive a control treatment that will be lotion with no melatonin, and there will be a week in between with no treatment at all.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any antidepressant, anti-anxiety, or sleep medications, including melatonin, to participate in this trial.

What data supports the effectiveness of the treatment Melatonin Lotion for sleep disorders?

Research shows that melatonin, when delivered through the skin (transdermal), can help improve sleep by reducing waking after sleep onset and promoting sleep during challenging times, like daytime for shift workers. This suggests that melatonin lotion might be effective for sleep disorders by maintaining sleep better than oral forms. ^{1 2 3 4 5}

Is melatonin lotion safe for humans?

Melatonin is generally considered safe for short-term use, but there are concerns about potential risks, especially with long-term use, in certain groups like children and people with epilepsy or asthma. ^{6 7 8 9 10}

How does melatonin lotion differ from other sleep disorder treatments?

Melatonin lotion offers a unique transdermal (through the skin) delivery method, which may provide more consistent melatonin levels and improve sleep maintenance compared to fast-release oral melatonin, especially during adverse circadian phases like shift work or jet lag. ^{1 3 4 5 11}

Research Team

Lisa E Olson, Ph.D.

Principal Investigator

University of Redlands

Eligibility Criteria

This trial is for young adults with sleep issues and mild symptoms of depression or anxiety. Participants must have specific scores on the PROMIS measures for sleep disturbance, anxiety, or depression to join.

Inclusion Criteria

My sleep disturbance score is 48 or higher.

T score ≥ 55 on the anxiety or depression short form PROMIS measures (mild symptoms or more)

Exclusion Criteria

I am currently taking medication for depression, anxiety, or sleep issues.

Pregnancy

Allergies/sensitivities to scented lotion

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive melatonin lotion or placebo lotion in a randomized crossover design for one week each, with a one-week washout period in between

3 weeks

3 visits (in-person) for equipment and sample return

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Melatonin Lotion

Trial Overview The study tests if melatonin lotion improves sleep quality and mental health in young adults. It involves comparing a placebo lotion (no active ingredient) with a melatonin-infused lotion over separate weeks, using surveys, actigraphs, heart rate monitors, and saliva samples.

Participant Groups

Group I: Placebo lotion first Experimental Treatment 2 Interventions

Participants will be randomized to one week of treatment with placebo lotion, followed by a week washout, then one week of treatment with melatonin lotion

Group II: Melatonin lotion first Experimental Treatment 2 Interventions

Participants will be randomized to one week of treatment with melatonin lotion, followed by a week washout, then one week of treatment with placebo lotion

Who Is Running the Clinical Trial?

University of Redlands

Lead Sponsor

Trials

4

Recruited

160+

Findings from Research

Melatonin shows potential as a treatment for sleep disorders related to melatonin deficiency, supported by basic research and initial clinical experiences.

However, more clinical studies are needed to confirm its effectiveness for other indications, as many findings from animal studies do not translate well to humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Melatonin: is there a rationale for the clinical use of this hormone in sleep therapy?]. Fauteck, JD.[2015]

Melatonin may improve sleep by correcting circadian phase abnormalities and has a modest direct sleep-inducing effect, particularly when taken during the day by younger individuals.

The effectiveness of melatonin is influenced by the dose, the type of subjects (like insomniacs or the elderly), and the timing of administration, suggesting that its mechanism of action involves specific receptors in the brain that help regulate the body's internal clock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? Sack, RL., Hughes, RJ., Edgar, DM., et al.[2022]

Melatonin significantly reduces the time it takes to fall asleep (by about 7 minutes) and increases total sleep time (by about 8 minutes) in patients with primary sleep disorders, based on a meta-analysis of 19 studies involving 1683 participants.

While the effects of melatonin on sleep quality are modest, it is considered a safer alternative to other insomnia medications due to its benign side-effect profile, making it a viable option for treating sleep issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis: melatonin for the treatment of primary sleep disorders. Ferracioli-Oda, E., Qawasmi, A., Bloch, MH.[2021]

Transdermal delivery of melatonin (MEL) can effectively increase plasma MEL levels and improve sleep maintenance in healthy individuals, particularly during the latter part of an 8-hour sleep opportunity.

This method may offer advantages over traditional oral melatonin, especially for shift workers or those experiencing jet lag, by promoting better sleep during challenging circadian phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of transdermal melatonin delivery to improve sleep maintenance during daytime. Aeschbach, D., Lockyer, BJ., Dijk, DJ., et al.[2021]

Melatonin effectively phase shifts circadian rhythms, making it a useful treatment for sleep disorders related to circadian misalignment, such as jet lag and shift work.

In specific conditions like delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake disorder, melatonin has been shown to advance sleep onset and improve overall sleep quality compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of melatonin in the treatment of phase shift and sleep disorders. Skene, DJ., Lockley, SW., Arendt, J.[2019]

A systematic review of 37 randomized controlled trials found that melatonin is generally safe and well tolerated, with only mild to moderate adverse events reported, such as daytime sleepiness and headache.

Despite the overall safety profile, the lack of long-term studies limits our understanding of potential risks, especially in vulnerable populations like children and those with epilepsy or asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review. Besag, FMC., Vasey, MJ., Lao, KSJ., et al.[2020]

In a 3-month study involving 22 women with moderate to severe skin aging, topical application of melatonin-based creams significantly reduced crow's feet wrinkles by 15% and improved skin tonicity by 30%.

The melatonin creams also led to a 59.5% reduction in skin dryness and a 26.5% improvement in surface microrelief, demonstrating their efficacy as an anti-aging treatment with good tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. Milani, M., Sparavigna, A.[2022]

Melatonin (MLT) showed the highest permeation through skin and buccal tissues when formulated with Montanov® 68 (M68) and sodium carboxymethylcellulose (NaCMC), suggesting these vehicles could enhance its systemic effects.

For local action in the skin and buccal mucosa, M68, poloxamer 407 (P407), and Pluronic® lecithin organogel (PLO) are recommended, while oral adhesive paste Orabase® (OB) was found to be the least effective vehicle.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin Delivery: Transdermal and Transbuccal Evaluation in Different Vehicles. Flo, A., Calpena, AC., Halbaut, L., et al.[2018]

A systematic review of 17 randomized controlled trials involving 651 participants found no evidence that exogenous melatonin effectively treats secondary sleep disorders or sleep disorders related to sleep restriction, such as jet lag and shift work disorder.

The review also indicated that melatonin is safe for short-term use (up to three months), showing no adverse effects in the studied populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. Buscemi, N., Vandermeer, B., Hooton, N., et al.[2018]

Melatonin treatment in children and adolescents with chronic insomnia does not appear to cause serious adverse events, but there is an increased risk of non-serious adverse events, with a relative risk of 1.56 based on 17 studies involving 1350 patients.

Long-term use of melatonin may have little to no effect on pubertal development in most cases, but there is a potential for delays in development after more than 7 years of treatment, highlighting the need for further research to clarify these long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment. Händel, MN., Andersen, HK., Ussing, A., et al.[2023]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

[Melatonin: is there a rationale for the clinical use of this hormone in sleep therapy?]. [2015]

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

Sleep-promoting effects of melatonin: at what dose, in whom, under what conditions, and by what mechanisms? [2022]

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

Meta-analysis: melatonin for the treatment of primary sleep disorders. [2021]

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

Use of transdermal melatonin delivery to improve sleep maintenance during daytime. [2021]

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

Use of melatonin in the treatment of phase shift and sleep disorders. [2019]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Adverse Events Associated with Melatonin for the Treatment of Primary or Secondary Sleep Disorders: A Systematic Review. [2020]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Antiaging efficacy of melatonin-based day and night creams: a randomized, split-face, assessor-blinded proof-of-concept trial. [2022]

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

Melatonin Delivery: Transdermal and Transbuccal Evaluation in Different Vehicles. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. [2018]

10. England pubmed.ncbi.nlm.nih.gov

The short-term and long-term adverse effects of melatonin treatment in children and adolescents: a systematic review and GRADE assessment. [2023]

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

Therapeutic potential of melatonin agonists. [2019]