Selenium Supplementation for Improving Depression in Children and Adolescents: Efficacy and Mechanistic Study

Not Applicable

Not yet recruiting

• Conditions: Depression - Major Depressive Disorder
• Interventions: Drug: selenium yeast supplementation; Drug: Placebo yeast supplementation

• Registration Number: NCT07203144
• Lead Sponsor: First Affiliated Hospital of Chongqing Medical University

Brief Summary

The purpose of this study is to investigate the role and mechanisms of selenium in depression among children and adolescents, aiming to provide new insights for understanding the pathogenesis and treatment of depression in this population.

Detailed Description

This randomized, double-blind, placebo-controlled trial will evaluate the efficacy and safety of selenium supplementation (selenium yeast) combined with fluoxetine in children and adolescents with major depressive disorder (MDD). Eligible participants are aged \[specific age range if applicable\], meet DSM-5 criteria for a current depressive episode, and have a CDRS-R score ≥40 confirmed by trained psychiatrists. A total of \[planned sample size\] participants will be randomized 1:1 to receive either fluoxetine plus selenium yeast or fluoxetine plus placebo. Selenium yeast will be administered at 100-200 μg/day. Fluoxetine will begin at 10 mg/day and may be adjusted by the treating psychiatrist within a range of 20-60 mg/day. The placebo consists of commercially available yeast tablets identical in appearance, taste, and size to selenium yeast, administered at 100-200 μg/day. Biological samples (blood, urine, stool) will be collected for routine laboratory tests, thyroid, liver, and kidney function, and serum will be analyzed for selenium and ferroptosis-related biomarkers. Brain MRI will also be performed. These assessments will be repeated at weeks 4 and 8 of treatment, together with rating scale evaluations and biospecimen collection. The primary outcome is the change in depressive symptoms, measured by the CDRS-R and Beck Depression Inventory (BDI). Secondary outcomes include anxiety symptoms (SCARED, HAMA), overall clinical improvement (CGI-S, CGI-I), manic symptoms (YMRS), suicide risk (C-SSRS), quality of life (PedsQL 4.0), sleep quality (PSQI), and rumination (RSS). Safety will be monitored through adverse events, vital signs, laboratory tests, and tolerability assessments. This study will provide preliminary evidence on the adjunctive role of selenium supplementation in fluoxetine treatment for adolescent depression and inform future large-scale trials.

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-09-24
• Study First Submitted QC: 2025-09-24
• Last Update Submitted: 2025-09-24
• Study Start: 2025-10-01
• Study First Posted: 2025-10-02
• Last Update Posted: 2025-10-02
• Primary Completion: 2027-04-01
• Study Completion: 2027-04-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 172

Inclusion Criteria

• Aged 12-18 years; diagnosed with major depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), using the K-SADS-PL diagnostic tool; a score of ≥28 on the Children's Depression Rating Scale-Revised (CDRS-R); adequate visual and auditory abilities to complete the study; willingness to participate in the study with informed consent signed by both the participant and a legal guardian.

Exclusion Criteria

• patients with severe psychiatric disorders such as bipolar disorder, schizophrenia, bulimia nervosa, anorexia nervosa, or primary obsessive-compulsive disorder; those with severe physical illnesses or other life-threatening conditions; patients in a current depressive episode with a clear suicidal plan or history of suicide attempt; individuals with a history of substance or drug abuse; those requiring immediate hospitalization for psychiatric disorders; patients currently taking medications contraindicated with the investigational drug or that may interfere with its efficacy; those who have received modified electroconvulsive therapy (MECT) within the past 12 months; individuals allergic to selenium yeast protein, including those with allergic rhinitis, gastrointestinal sensitivity, allergic constitution, or autoimmune diseases such as Graves' disease or Hashimoto's thyroiditis; patients with contraindications to magnetic resonance imaging (MRI); and left-handed individuals.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluoxetine combined with selenium yeast therapy	selenium yeast supplementation	In this group, participants will receive standard fluoxetine treatment along with adjunctive selenium yeast supplementation at a daily dose of 100-200 μg, aiming to investigate the role and mechanisms of selenium yeast in fluoxetine therapy.
Fluoxetine combined with placebo therapy	Placebo yeast supplementation	Participants in this group, in addition to receiving conventional fluoxetine treatment, were administered 100-200 µg per day of a placebo identical in appearance and odor to selenium yeast as adjunctive therapy. The aim was to investigate the role of selenium yeast in fluoxetine treatment and to clarify whether it enhances the therapeutic effect.

Primary Outcome Measures

Name	Time	Method
Change in CDRS-R (Children's Depression Rating Scale) scores from baseline	Week 4 and Week 8 of treatment	Clinical response (≥ 50% reduction in CDRS-R scores from baseline)

Secondary Outcome Measures

Name	Time	Method
Change in BDI-II (Baker Depression Scale) scores from baseline	Week 4 and Week 8 of treatment	Change in BDI-II (Baker Depression Scale) scores from baseline
Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline	Week 4 and Week 8 of treatment	Improvement in anxiety (SCARED minus the scores）
Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale)	Week 4 and Week 8 of treatment	The severity of the suicide risk
Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline	Week 4 and Week 8 of treatment	Improvement in sleep status (PSQI minus the scores）
Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline	Week 4 and Week 8 of treatment	Improvement of children's quality of life（PedsQL4.0 minus the scores)
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline	Week 4 and Week 8 of treatment	Improvement in overall clinical impression severity ( 7-point scale, with 1 being normal and 7 being among the most severely damaged )
Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline	Week 4 and Week 8 of treatment	Improvement of clinical general Impression scale (7-point scale,7 denoting a very significant deterioration)
Change in RSS (Ruminative Responses Scale)	Week 4 and Week 8 of treatment	The level of improvement in negative thinking(the higher the total score, the more reflective thinking the more severe it is).

Trial Locations

Locations (1)

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, Chongqing Municipality, China