Efficacy of Melatonin, Low-dose Quetiapine, or Placebo in Patients With Psychiatric Disorders and Comorbid Insomnia (MEL-QUE)

Efficacy of Melatonin, Low-dose Quetiapine, or Placebo in Patients With Psychiatric Disorders and Comorbid Insomnia: a Randomized Clinical Trial

The goal of this investigator-initiated, randomized, blinded, 3-armed placebo-controlled, pragmatic, clinical superiority trial is to examine the efficacy of melatonin or low-dose quetiapine versus placebo for treatment of insomnia in patients with psychiatric disorders. The aims of the study are:

• To examine the efficacy of melatonin or low-dose quetiapine versus placebo for treatment of insomnia
• To examine how melatonin or low-dose quetiapine affects global symptom severity, sleep quality, psychosocial functioning and subjective well-being.

Participants will receive six weeks of treatment with either melatonin, quetiapine or placebo followed by a brief taper off.

Study Overview

• Status: Recruiting
• Conditions: Insomnia; Psychiatric Disorders
• Intervention / Treatment: Drug: Melatonin; Drug: Quetiapine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 255
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Lone Baandrup, MD; Phone Number: +4591165903; Email: lone.baandrup@regionh.dk

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Recruiting
    • Mental Health Center Copenhagen
    • Contact: Ursula Brinck-Claussen, MD; Phone Number: +4520483136; Email: ursula.oedum.brinck-claussen@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 16 to 64 years of age
• ICD-10 diagnosis of a current or previous mental or behavioral disorder (F20-F69, F84, F90-95)
• For the diagnoses F84 and F90 a previous period of treatment with melatonin is required
• For the 16-17 years old: Non-pharmacological treatment options including sleep hygiene education, weighted blanket or other gravity products have been tested with insufficient effect
• Self-reported sleep difficulties at least three times per week in the preceding 3 months
• Insomnia Severity Index score ≥11
• Women of childbearing potential: negative pregnancy test at baseline and use of highly effective contraception measures
• Informed consent

Exclusion Criteria:

• Current treatment with melatonin or quetiapine
• Severe somatic comorbidity
• BMI ≥ 35 kg/m2
• Breastfeeding
• Alcohol and/or substance dependency within the last 3 months
• Inadequate Danish language skills
• Not able to make an informed consent
• Increased cardiac risk as assessed by presence of cardiac risk factors, cardiac symptoms, or prolonged QT-interval at baseline ECG

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 1-3 capsules flexible dosing before bed time
Experimental: Melatonin	Drug: Melatonin; 3-9 mg flexible dosing before bed time
Experimental: Quetiapine	Drug: Quetiapine; 50-150 mg flexible dosing before bed time

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia severity	Insomnia Severity Index, range 0-28, higher is worse	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical global impression (CGI)	Clinical global impression: Severity, range 0-7, higher is worse	6 weeks
Subjective sleep quality	Pittsburgh Sleep Quality Index, range 0-21, higher is worse	6 weeks
Psychosocial functioning	Personal and Social Performance Scale, range 1-100, higher is better	6 weeks
Patient-reported subjective well-being	WHO-5 well-being index, range 0-100, higher is better	6 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective sleep quality (polysomnography)	Total sleep time in minutes, higher is better	6 weeks
Circadian rhythmicity (actigraphy)	Interdaily stability which quantifies the invariability from day to day, i.e., the predictability of the 24 h rest-activity pattern. This index will be 1 for perfect interdaily stability and thus lower values reflect higher variability between the observed days	6 weeks

Collaborators and Investigators

• Sponsor: Lone Baandrup
• Collaborators: Region Capital Denmark; Mental Health Services in the Capital Region, Denmark; Danish Center for Sleep Medicine; Copenhagen Trial Unit, Center for Clinical Intervention Research
• Investigators: Principal Investigator: Lone Baandrup, MD, Mental Health Center Copenhagen

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2023
• Primary Completion (Estimated): February 28, 2029
• Study Completion (Estimated): February 28, 2029

Study Registration Dates

• First Submitted: September 13, 2023
• First Submitted That Met QC Criteria: September 25, 2023
• First Posted (Actual): October 2, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Behavioral Symptoms; Sleep Wake Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Problem Behavior; Mental Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Antioxidants; Protective Agents; Antidepressive Agents; Antipsychotic Agents; Quetiapine Fumarate; Melatonin
• Other Study ID Numbers: 2023-504728-24-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available for meta-analysis. Proposals should be directed to: lone.baandrup@regionh.dk. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: After publication of planned primary, secondary and exploratory outcomes. There will be no end date for availability of data.
• IPD Sharing Access Criteria: Meta-analytical purposes
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No