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Adjunctive melatonin or digital cognitive behavioural therapy for insomnia (dCBT-I) may be more effective than pill placebo at reducing depressive symptoms in young adults with mood disorders

The MELODY trial is a phase 3 randomised controlled trial testing whether 12 weeks of adjunctive melatonin or dCBT-I are more effective than pill placebo at reducing depressive symptoms in 660 young people aged 18-30 years with major depressive disorder or bipolar II disorder and significant sleep complaints. The primary outcome is depressive symptoms at week 12, measured by the Quick Inventory of Depressive Symptomatology, Adolescent version. This is a study protocol, so no results are reported yet.

Last updated: Aug 26, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score44/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. MELODY trial: study protocol for a 12-week randomised controlled trial of adjunctive melatonin, digital cognitive behavioural therapy for insomnia or pill placebo to improve depressive symptoms in young adults with mood disorders.

observational

Crouse JJ, Shin M, Hockey SJ, Jeon E, Bradshaw N, Nichles A, Zmicerevska N, Chong MK, You H, Wray NR, Scott J, Grunstein RR, Naismith SL, Merikangas KR, Cain SW, Medland SE, Iorfino F, Uebergang TD, McKenna S, Carpenter JS, Tonini E, Bhattacharya N, Hamilton BA, Wallace LM, Henders AK, Scott EM, Song YJC, Hickie IB · BMJ open (2026)

Participants: N/A
Duration: 12 weeks (plus 6-month follow-up)
Intervention: 12 weeks of adjunctive melatonin (dose not specified) or digital cognitive behavioural therapy for insomnia (dCBT-I), compared to pill placebo
Outcome: Depressive symptoms (Quick Inventory of Depressive Symptomatology, Adolescent version) at week 12; secondary outcomes include partial remission of major depressive episode, other mental health symptoms, sleep, functioning, quality of life
Effect Size: N/A (protocol, no results)
Population: Young adults aged 18-30 years with SCID-5 diagnosis of Major Depressive Disorder or Bipolar Disorder type II, moderate to severe depressive symptoms, and significant sleep or sleep-wake complaints

Result:

PubMed: 42637255DOI: 10.1136/bmjopen-2025-114817

Mechanism Graph

Sleep and circadian rhythm disturbances are proposed to be pathophysiological mechanisms in mood disorders
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Interventions target sleep and circadian rhythms (melatonin, dCBT-I)
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Mediation analyses will test whether sleep or circadian rhythm changes play a causal role in antidepressant effects
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If sleep/circadian changes mediate improvement, this supports the causal pathway

Limitations

  • ⚠Open-label design for dCBT-I arm may introduce bias
  • ⚠Single-centre trial may limit generalizability
  • ⚠No results yet; protocol only

Frequently Asked Questions

What is the MELODY trial testing?▼

It is testing whether 12 weeks of adjunctive melatonin or digital cognitive behavioural therapy for insomnia (dCBT-I) are more effective than pill placebo at reducing depressive symptoms in young adults with mood disorders.

Who can participate in the MELODY trial?▼

Young adults aged 18-30 years with a diagnosis of major depressive disorder or bipolar II disorder, moderate to severe depressive symptoms, and significant sleep or sleep-wake complaints.

What is the primary outcome of the MELODY trial?▼

The primary outcome is depressive symptoms at week 12, measured by the Quick Inventory of Depressive Symptomatology, Adolescent version.

How will the MELODY trial determine if sleep therapies work as antidepressants?▼

It will use mediation analyses to test whether changes in sleep or circadian rhythms play a causal role in antidepressant effects.

Products

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References

  1. 1.Crouse JJ, Shin M, Hockey SJ, Jeon E, Bradshaw N, Nichles A, Zmicerevska N, Chong MK, You H, Wray NR, Scott J, Grunstein RR, Naismith SL, Merikangas KR, Cain SW, Medland SE, Iorfino F, Uebergang TD, McKenna S, Carpenter JS, Tonini E, Bhattacharya N, Hamilton BA, Wallace LM, Henders AK, Scott EM, Song YJC, Hickie IB. "MELODY trial: study protocol for a 12-week randomised controlled trial of adjunctive melatonin, digital cognitive behavioural therapy for insomnia or pill placebo to improve depressive symptoms in young adults with mood disorders.." BMJ open, 2026. PMID: 42637255 DOI: 10.1136/bmjopen-2025-114817
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.