RecruitingPhase 3ACTRN12624000017527

MELODY Trial: A 12-week randomised controlled trial of adjunctive melatonin or digital cognitive behavioural therapy for insomnia, or placebo to improve depressive symptoms in young adults with mood disorders

Sponsor

The University of Sydney

Enrollment

660 participants

Start Date

Aug 7, 2025

Study Type

Interventional

Conditions

Bipolar Disorder Type II Depression Sleep Disturbance

Summary

Melatonin is considered safe, cost-effective, and scalable, thus, a justifiable intervention for circadian mood disorders. To counter the previous clinical trials design flaws, the present study will employ a larger sample size allowing for high statistical power of analyses. Additionally, in the proposed target treatment approach, patients will be stratified based on SCRDs (Sleep and Circadian Rhythm Disturbance) to enhance the potential effectiveness of the intervention. In a recent proof-of-concept study utilizing agomelatine, a melatonin agonist and serotonin antagonist, for the treatment of major depressive disorder, adults with depression had significantly reduced symptoms after the intervention (Robillard et al., 2018). Moreover, sleep disturbances were significantly reduced, and a strong correlation between relative improvements in depression severity and some components of circadian rhythm disturbances was reported (Robillard et al., 2018). The overall aim of the study is to examine whether melatonin is a more effective early intervention for youth with depression and SCRDs compared to dCBT-I alone. Additionally, the study aims to investigate whether improvements in SCRDs causally mediate changes in depressive symptoms. The outcomes of this clinical trial will hold significant implications for early intervention in mood disorders. The findings have the potential to validate and strengthen the hypothesis that individuals with circadian depression may respond more favourably to sleep and circadian-based interventions, such as melatonin. This, in turn, could have transformative implications for personalised interventions in the treatment of mood disorders.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 30 Yearss

Plain Language Summary

Simplified for easier understanding

The MELODY Trial is testing whether melatonin — a natural sleep hormone available in supplement form — can improve depression symptoms in young adults who also have disrupted sleep or body clock rhythms. Many people with depression experience significant sleep problems, and researchers believe that addressing the body clock disruption directly, rather than just treating mood, might lead to better outcomes. The trial compares melatonin, a digital form of Cognitive Behavioural Therapy for Insomnia (dCBT-I), and a placebo across 12 weeks. Participants will be randomly assigned to one of three groups and will take either melatonin, a digital therapy program, or placebo tablets each night. Researchers will track changes in depression severity, sleep quality, and circadian rhythm patterns over the course of the trial. The goal is to find out whether improving the body clock can directly reduce depressive symptoms, and whether melatonin is more effective than digital sleep therapy alone for this purpose. You may be eligible if you are aged 18 to 30, have a diagnosis of Major Depressive Disorder or Bipolar II Disorder with a current depressive episode, and have significant sleep or sleep-wake cycle problems. You are not eligible if you have taken melatonin in the past six weeks, have a psychotic disorder, currently use certain medications such as Warfarin or modafinil, or have recently done night shift work or crossed multiple time zones.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

Eligible participants who meet all inclusion criteria will be randomly assigned to one of three study arms: Melatonin, Placebo, or Digital Cognitive Behavioural Therapy for Insomnia (dCBT-i). The intervention period for all groups is 12 weeks, with a follow-up assessment conducted at Week 26. Participants in the Melatonin and Placebo arms will be instructed to take a 2 mg capsule (instant-release melatonin or placebo) nightly, approximately two hours before their desired bedtime. Following a safety assessment at Week 5, the dose will be increased to 4 mg (two capsules per night). Participants assigned to the dCBT-i arm will receive access to the online program, Sleep Healthy Using the Internet (SHUTi), and will be instructed to complete six modules over the 12-week intervention period. All participants will continue to receive Treatment As Usual (TAU) from their treating clinician throughout the study. Study-related activities—including self-report questionnaires and clinical assessments—will be completed at baseline, Week 4, Week 8, end of treatment (Week 12), and follow-up (Week 26). These assessments may be conducted either in-person or online, depending on participant preference and availability. To ensure participant safety and monitor progress, the study team will conduct fortnightly check-ins throughout the intervention period.