Efficacy of Melatonin and Low-Dose Quetiapine in Adolescents with Psychiatric Disorders and Comorbid Insomnia: A Randomized, Placebo-Controlled Trial

The primary objective of this randomized clinical trial is to evaluate the **efficacy** of melatonin or low-dose quetiapine compared to placebo in the treatment of **insomnia** in adolescents with psychiatric disorders. This is clinically relevant as insomnia is a common comorbidity in psychiatric conditions, and effective management can significantly improve overall patient outcomes.

Secondary objectives include examining how melatonin or low-dose quetiapine affects global symptom severity, sleep quality, psychosocial functioning, and subjective well-being. These factors are crucial for understanding the broader impact of these treatments on the quality of life and daily functioning of adolescents with psychiatric disorders.

The clinical trial involves **participants** aged 16 to 17 years, both male and female, who have been diagnosed with a current or previous **psychiatric disorder** as per ICD-10 codes F20-F69, F84, F90-F95, and experience insomnia. The study population was selected based on specific criteria, including self-reported sleep difficulties occurring at least three times per week over the preceding three months and an Insomnia Severity Index score of 11 or higher. Participants must have previously attempted non-pharmacological treatments such as sleep hygiene education or the use of weighted blankets with insufficient results. For those with diagnoses F84 and F90, a prior period of treatment with melatonin is required. Women of childbearing potential are required to have a negative pregnancy test at baseline and must use highly effective contraception measures. Informed consent is obtained from both the minor and their legally designated representative. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **efficacy** of **melatonin** and low-dose **quetiapine** compared to a placebo in adolescents with psychiatric disorders and comorbid insomnia. This study is a randomized, double-blind, controlled trial, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thus minimizing bias. The trial is expected to commence on January 31, 2025, and conclude by February 28, 2029, with a maximum treatment period of six months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (16 to 17 years), a diagnosis of a psychiatric disorder according to ICD-10 codes, and a history of sleep difficulties. Following successful screening, participants will be randomized to receive either melatonin, quetiapine, or a placebo, all administered orally in the form of film-coated tablets. The primary endpoint of the study is the assessment of insomnia severity using the Insomnia Severity Index (ISI), while secondary endpoints include evaluations of clinical global impression, subjective sleep quality, psychosocial functioning, and patient-reported well-being.

Throughout the trial, participants will attend regular follow-up visits to monitor treatment efficacy and safety, as well as to collect data on secondary endpoints. The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments will be conducted. The expected length of participant involvement is up to six months, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with study procedures. The trial aims to provide valuable insights into the therapeutic potential of melatonin and quetiapine for managing insomnia in adolescents with psychiatric conditions.

The clinical trial involves the administration of **Melatonin** Orifarm 3 mg film-coated tablets. The active substance in this experimental medication is melatonin, a chemical compound. The pharmaceutical form is a film-coated tablet, and the medication is administered orally. The maximum daily dose is 9 mg, with a total maximum dose of 378 mg over the treatment period. The treatment period is set for a maximum of 6 weeks. The tablets are encapsulated in lactose-containing gelatin capsules to facilitate administration. Participant compliance will be monitored through regular assessments and pill counts.

Another experimental medication used in the trial is **Quetiapine** Sandoz 25 mg film-coated tablets. The active substance is quetiapine, also a chemical compound. This medication is provided in the form of film-coated tablets and is administered orally. The maximum daily dose is 150 mg, with a total maximum dose of 6300 mg over the treatment period. Similar to the melatonin tablets, the quetiapine tablets are encapsulated in lactose-containing gelatin capsules. The treatment period is also set for a maximum of 6 weeks, and participant compliance will be monitored through regular assessments and pill counts.

The trial also includes a placebo group, which will receive starch and lactose-containing gelatin capsules. These capsules do not contain any active pharmaceutical ingredients and serve as a comparator treatment to evaluate the efficacy of the experimental medications. The placebo is administered orally, and the treatment period is consistent with the experimental groups, lasting up to 6 weeks. Compliance in the placebo group will be monitored in the same manner as the experimental groups.

The efficacy of the treatment in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the evaluation of **insomnia severity** using the Insomnia Severity Index (ISI). This validated scale will be employed to measure changes in insomnia symptoms over the course of the trial. Secondary endpoints include several measures: Clinical Global Impression (CGI), subjective sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI), psychosocial functioning evaluated through the Personal and Social Performance Scale (PSP), patient-reported subjective well-being using the WHO-5 well-being index, and assessments of rest-sleep-activity cycles and physiological variables.

Data collection will occur at specified intervals throughout the trial, with the schedule for these assessments designed to capture both short-term and long-term effects of the treatment. The trial will compare the efficacy of melatonin and low-dose quetiapine against a placebo in adolescents with psychiatric disorders and comorbid insomnia. The trial is structured to ensure rigorous evaluation of treatment outcomes, with the use of standardized and validated instruments to ensure the reliability and validity of the efficacy assessments.