Melatonin for Insomnia

Overseen By Diane B Boivin, MD, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Douglas Mental Health University Institute

Disqualifiers: Psychopathology, Gynecological pathology, Sleep apnea, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a slow-release melatonin pill to help postmenopausal women with sleep problems. The pill works by mimicking the body's natural sleep hormone to regulate sleep patterns. Melatonin has been studied extensively for its sleep-promoting effects in various populations, including the elderly and those with sleep disorders.

Will I have to stop taking my current medications?

Yes, participants need to be drug-free at the time of the study.

What evidence supports the effectiveness of the drug melatonin for treating insomnia?

Research shows that prolonged-release melatonin (Circadin) improves sleep quality and morning alertness in older adults with insomnia, without causing dependency or significant side effects. It mimics the body's natural hormone pattern, helping to regulate sleep cycles effectively. ^{1 2 3 4 5}

Is melatonin safe for treating insomnia?

Melatonin, including formulations like Circadin and PedPRM, is generally considered safe for treating insomnia, with studies showing no significant adverse effects compared to placebo. It does not impair cognitive skills or cause dependence, and common side effects are mild, such as nausea and dizziness. ^{1 2 6 7 8}

How does the drug melatonin differ from other treatments for insomnia?

Melatonin is unique because it is a hormone that naturally regulates sleep-wake cycles, and its prolonged-release forms like Circadin and PedPRM are designed to improve sleep efficiency without the risk of dependency. Unlike some other sleep medications, melatonin works by aligning the body's internal clock, making it particularly useful for treating circadian rhythm disorders and insomnia in specific populations, such as the elderly and children with autism spectrum disorder. ^{6 7 8 9 10}

Research Team

Diane B Boivin, MD, PhD

Principal Investigator

Douglas Hospital Research Centre

Eligibility Criteria

This trial is for postmenopausal women with insomnia, who have trouble sleeping at least three nights a week and it's been going on for over three months. They should not be heavy users of coffee, tobacco, or alcohol and must not have any psychological conditions or other medical issues that could interfere with the study.

Inclusion Criteria

You are not currently taking any medications and have only used moderate amounts of coffee, tobacco, alcohol, or other substances in the past.

I am a woman with insomnia for 3 months due to menopause.

I am a postmenopausal woman who has not had a period for at least 12 months.

Exclusion Criteria

You have worked night shifts or traveled across more than 2 time zones in the 2 months before the study.

You show signs of mental health issues during specific interviews and questionnaires.

I have not had any gynecological conditions or surgeries that could affect this study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ambulatory Phase 1

Participants receive either melatonin or placebo for 15 days, taking 2 mg of exogenous melatonin in a slow release formulation (or placebo) 60 mins prior to bedtime.

2 weeks

Home-based, daily administration

Wash-out Period

Participants stop taking their melatonin/placebo pills for at least 2 weeks before switching treatments.

2 weeks

Ambulatory Phase 2

Repetition of Ambulatory Phase 1 with the opposite treatment (melatonin or placebo).

2 weeks

Home-based, daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment.

4 weeks

Treatment Details

Interventions

• Melatonin
• Placebo

Trial Overview The study tests if taking melatonin (a sleep hormone) helps improve sleep in these women. It's a crossover study where participants will use either melatonin or a placebo without knowing which one they're taking first, then switch after 15 days.

Participant Groups

Group I: Melatonin Experimental Treatment 1 Intervention

2 mg oral tablet, melatonin slow release formulation, 1x 60 min before bedtime for 15 days

Group II: Placebo Placebo Group 1 Intervention

2 mg oral tablet, 1x 60 min before bedtime for 15 days

Melatonin is already approved in European Union, United States for the following indications:

Approved in European Union as Circadin for:

• Insomnia in adults aged 55 and over
• Sleep disorders in children with autism spectrum disorder

Approved in European Union as Slenyto for:

• Insomnia in children and adolescents aged 2-18 with autism spectrum disorder

Approved in United States as Melatonin for:

• Sleep disorders in children with autism spectrum disorder
• Insomnia in adults

Who Is Running the Clinical Trial?

Douglas Mental Health University Institute

Lead Sponsor

Trials

31

Recruited

2,800+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Findings from Research

Circadin, a prolonged-release melatonin formulation, effectively improves sleep quality and reduces sleep latency in patients aged 55 and over with primary insomnia, showing benefits in next-day alertness and overall quality of life.

Unlike traditional sedative hypnotics, Circadin does not impair cognitive or psychomotor skills, has no risk of dependence or abuse, and has a favorable safety profile with no significant adverse events compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. Zisapel, N.[2013]

In a postmarketing surveillance study of 653 patients aged 55 and older, prolonged-release melatonin (PRM) significantly improved sleep quality from an average score of 4.2 to 2.6 and morning alertness from 4.0 to 2.5 over three weeks of treatment.

PRM demonstrated a low incidence of rebound insomnia (3.2% early withdrawal, 2.0% late withdrawal) and was well tolerated, with minimal adverse effects, suggesting it is a safe and effective alternative to traditional hypnotics for managing insomnia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. Hajak, G., Lemme, K., Zisapel, N.[2021]

In a study of 13 totally blind subjects, prolonged-release melatonin (PRM) improved mean nightly sleep duration by 43 minutes compared to 16 minutes in the placebo group, suggesting it may help with sleep difficulties in this population.

PRM was well-tolerated with mild to moderate adverse events, and its beneficial effects on sleep persisted even after discontinuation, indicating potential for stabilizing the biological clock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Roth, T., Nir, T., Zisapel, N.[2022]

Melatonin, particularly in the form of prolonged-release preparations like Circadin®, has been shown to improve sleep quality and reduce sleep latency in older adults, with a well-tolerated dosage of 2 mg once daily over 3 months.

Circadin® does not produce rebound effects or cognitive impairments commonly associated with traditional hypnotics, making it a safer first-line treatment option for insomnia in patients aged 55 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia]. Quera-Salva, MA., Claustrat, B.[2019]

Melatonin is a hormone that helps regulate sleep-wake cycles and has been used to treat various sleep disorders, including jet lag and insomnia.

Prolonged-release melatonin (Circadin) has recently been licensed in the UK specifically for treating primary insomnia, suggesting it may be an effective option for managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melatonin for primary insomnia? [2017]

Prolonged-release melatonin (Ped-PRM) has been approved as a pediatric treatment for insomnia in children and adolescents with autism spectrum disorder (ASD), showing safety for short-term use and no adverse effects on growth or development over the long term.

Melatonin is rapidly absorbed and metabolized, with immediate-release formulations being short-acting, while Ped-PRM provides sustained therapeutic levels throughout the night, highlighting the need for dose optimization due to variability in how individuals metabolize the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. Zisapel, N.[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]

References

1. Israel pubmed.ncbi.nlm.nih.gov

[Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drugs]. [2013]

2. England pubmed.ncbi.nlm.nih.gov

Lasting treatment effects in a postmarketing surveillance study of prolonged-release melatonin. [2021]

3. England pubmed.ncbi.nlm.nih.gov

The importance of timing in melatonin administration in a blind man. [2019]

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

Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. [2022]

5. France pubmed.ncbi.nlm.nih.gov

[Melatonin: Physiological and pharmacological aspects related to sleep: The interest of a prolonged-release formulation (Circadin®) in insomnia]. [2019]

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

Melatonin for primary insomnia? [2017]

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

Assessing the potential for drug interactions and long term safety of melatonin for the treatment of insomnia in children with autism spectrum disorder. [2022]

8. France pubmed.ncbi.nlm.nih.gov

Ramelteon: application withdrawn. Ramelteon in insomnia: withdrawal of marketing application in patients' best interests. [2014]

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

Therapeutic potential of melatonin agonists. [2019]

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

Role of melatonin in the regulation of human circadian rhythms and sleep. [2022]