Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I)

Phase 4

Not yet recruiting

• Conditions: Major Depressive Disorder (MDD)
• Interventions: Drug: Sertraline; Drug: Agomelatine; Drug: Aripiprazole

• Registration Number: NCT07011693
• Lead Sponsor: Xinyu Zhou

Brief Summary

This project aims to investigate the effectiveness of existing common antidepressants in adolescents with MDD who did not respond to their first treatment.

Detailed Description

This project aims to investigate the effectiveness of existing common antidepressants in adolescents with MDD who did not respond to their first treatment. Adolescents ages 12 to 17, currently taking a prescribed selective serotonin reuptake inhibitor (SSRI) at least 8 weeks and still experiencing depression, participate in a 8-week randomized treatment study that includes one of three conditions: (1) switching to sertraline , (2) switching to duloxetine , (3) augmentation of their original SSRI with aripiprazole.

Study Timeline

• Study First Submitted: 2025-05-26
• Status Verified: 2025-06
• Study First Submitted QC: 2025-06-05
• Last Update Submitted: 2025-06-05
• Study First Posted: 2025-06-10
• Last Update Posted: 2025-06-10
• Study Start: 2025-06-20
• Primary Completion: 2027-06
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

1. Aged 12-17;
2. As assessed by K-SADS-PL, it meets the DSM-5 criteria for MDD;
3. CDRS-R≥45;
4. CGI-S≥4;
5. Failed to respond to an initial SSRI trial: the trial at least 8 weeks, with the last of which were at a dosage of at least 40 mg per day of fluoxetine or its equivalent.

Exclusion Criteria

1. Current or lifetime diagnosis of bipolar disorder, schizophrenia, autism, attention-deficit/hyperactivity disorder or obsessive-compulsive disorder or psychosis not otherwise specified;
2. MDD with psychotic symptoms;
3. YMRS>13;
4. Current or lifetime diagnosis of serious neurologic diseases such as epilepsy, brain trauma or other serious physical illnesses;
5. Failure to respond adequately to two or more antidepressant treatment trials of recommended dose and length (at least 8 weeks, with the last 4 of which were at a dosage of at least 40 mg per day of fluoxetine or its equivalent);
6. History of clear-cut intolerability of, or lack of effect with, an adequate trial of sertraline, agomelatine, or aripiprazole;
7. Current depressive episode with clear suicidal plans or behaviors;
8. Received modified electroconvulsive therapy within 3 months;
9. Taking any medicine that contraindicates in combination with or interferes with the efficacy of the treatment;
10. Substance abuse or dependence;
11. Female patients with pregnancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group1-sertraline	Sertraline	dosage form: po dosage:25-200mg frequency:qd duration: patients will be given sertraline as a switching treatment to SSRI.
Group 2-agomelatine	Agomelatine	dosage form: po dosage:25-50mg frequency:qd duration: patients will be given agomelatine as a switching treatment to SSRI.
Group 3-aripiprazole with original SSRI	Aripiprazole	dosage form: po dosage: 1.25-15mg frequency:qn duration: patientswill be given aripiprazole as an add-on treatment to original SSRI.

Primary Outcome Measures

Name	Time	Method
response rate of Children's Depression Rating Scale (CDRS-R) scores	Baseline of treatment period, 4 weeks, 8 weeks	The primary outcomes are the treatment response rate (reduction rate of CDRS-R≥50%). The CDRS-R is a scale consisting of 17 items that are evaluated by clinicians to assess the intensity of depressive symptoms in adolescents, with items scored on scales of 1 to 5 or 1 to 7, resulting in a possible total score range of 17 to 113，higher scores mean a worse outcome.

Secondary Outcome Measures

Name	Time	Method
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline	Baseline of treatment period, 4 weeks, 8 weeks,	Improvement in overall clinical impression severity（ 7-point scale, with 1 being normal and 7 being among the most severely damaged
Adverse Event (AE) or Serious Adverse Event (SAE)	Baseline of treatment period, 1 month, 2 months,	Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale), Adverse Event (AE) or Serious Adverse Event (SAE)
Change in Baker Depression Scale（BDI-II) scores from baseline	Baseline of treatment period, 4 weeks, 8 weeks	Change in BDI-II scores from baseline，The BDI is a self-report rating scale containing 21 items. Based on the BDI scores, depression can be classified into six levels: normal (1-10), mild mood disorder (11-16), borderline clinical depression (17-20), moderate depression (21-30), severe depression (31-40), and extreme depression (over 40).Higher scores mean a worse outcome.
Change in The Screen for Child Anxiety-Related Emotional Disorders (SCARED) scores from baseline	Baseline of treatment period, 4 weeks，8 weeks	The SCARED is employed to evaluate child anxiety symptoms. Each question is rated from 0 to 2, with 0 denoting "not true or hardly ever true," 1 denoting "somewhat true or sometimes true", and 2 denoting "extremely true or often true". The maximum total score is 63. Higher scores mean a better or worse outcome.

Trial Locations

Locations (1)

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