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.
This article is automatically generated from the structured evidence profile behind the claim above. Scores reflect the quality and quantity of available research, not clinical advice.
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 current body of evidence comprises 1 study, including 1 randomized controlled trial. EvidenceHub rates the overall confidence at 44/100 (low).
The Claim
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
This conclusion is most relevant to: 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.
What the Research Shows
The conclusion draws on 1 linked study. Highlights from the cited literature:
- ▸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) —
How It Works
The proposed biological pathway:
- ▸Sleep and circadian rhythm disturbances are proposed to be pathophysiological mechanisms in mood disorders
- ▸Interventions target sleep and circadian rhythms (melatonin, dCBT-I)
- ▸Mediation analyses will test whether sleep or circadian rhythm changes play a causal role in antidepressant effects
- ▸If sleep/circadian changes mediate improvement, this supports the causal pathway
Who Might Benefit
Evidence fit by 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
Recommended Dose
Melatonin dose not specified in abstract
Limitations & Caveats
Important context when interpreting this evidence:
- ▸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.
References
- 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