Major Depressive Disorder (MDD)Phase 4SMART-INCT07011693
Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I)
A Phase 4 study testing Sertraline, Agomelatine and Aripiprazole in people with Major Depressive Disorder (MDD), run by Xinyu Zhou at 1 site in China.
Trial summary
This project aims to investigate the effectiveness of existing common antidepressants in adolescents with MDD who did not respond to their first treatment. Read more about this study
- Who is it for?
- Ages 12 to 17 years
- Conditions the study is for
- Major Depressive Disorder (MDD)
- What is being tested?
- Sertraline, Agomelatine and Aripiprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 1 siteChina
- Study dates
- 20 Jun 2025to Dec 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Aged 12-17;
- As assessed by K-SADS-PL, it meets the DSM-5 criteria for MDD;
- CDRS-R≥45;
- CGI-S≥4;
- 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.
Who cannot join
- Current or lifetime diagnosis of bipolar disorder, schizophrenia, autism, attention-deficit/hyperactivity disorder or obsessive-compulsive disorder or psychosis not otherwise specified;
- MDD with psychotic symptoms;
- YMRS>13;
- Current or lifetime diagnosis of serious neurologic diseases such as epilepsy, brain trauma or other serious physical illnesses;
- 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);
- History of clear-cut intolerability of, or lack of effect with, an adequate trial of sertraline, agomelatine, or aripiprazole;
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- Current depressive episode with clear suicidal plans or behaviors;
- Received modified electroconvulsive therapy within 3 months;
- Taking any medicine that contraindicates in combination with or interferes with the efficacy of the treatment;
- Substance abuse or dependence;
- Female patients with pregnancy.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, 400016
Xinyu Zhou, 2912-89012912, zhouxinyu@cqmu.edu.cn
About this study
Official title: Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I): An Open-Label, Multicenter, Randomized Controlled Trial
This project aims to investigate the effectiveness of existing common antidepressants in adolescents with MDD who did not respond to their first treatment.
Read the 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.
- Conditions
- Major Depressive Disorder (MDD)
- Being tested
- Sertraline, Agomelatine, Aripiprazole
- Keywords
- adolescent, SSRI, depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
Commonly used oral antipsychotics intervention therapy.
AgomelatineDrug
Commonly used oral antipsychotics intervention therapy.
AripiprazoleDrug
Commonly used oral antipsychotics intervention therapy.
| Study group | Role | What they receive |
|---|---|---|
| Group1-sertraline | Experimental | dosage form: po dosage:25-200mg frequency:qd duration: patients will be given sertraline as a switching treatment to SSRI. Receives: Drug: Sertraline |
| Group 2-agomelatine | Experimental | dosage form: po dosage:25-50mg frequency:qd duration: patients will be given agomelatine as a switching treatment to SSRI. Receives: Drug: Agomelatine |
| Group 3-aripiprazole with original SSRI | Experimental | dosage form: po dosage: 1.25-15mg frequency:qn duration: patientswill be given aripiprazole as an add-on treatment to original SSRI. Receives: Drug: Aripiprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
response rate of Children's Depression Rating Scale (CDRS-R) scores
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.
Measured: Baseline of treatment period, 4 weeks, 8 weeks
Secondary outcomes (4)
Change in Baker Depression Scale（BDI-II) scores from baseline
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.
Measured: Baseline of treatment period, 4 weeks, 8 weeks
Change in The Screen for Child Anxiety-Related Emotional Disorders (SCARED) scores from baseline
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.
Measured: Baseline of treatment period, 4 weeks，8 weeks
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline
Improvement in overall clinical impression severity（ 7-point scale, with 1 being normal and 7 being among the most severely damaged
Measured: Baseline of treatment period, 4 weeks, 8 weeks,
Adverse Event (AE) or Serious Adverse Event (SAE)
Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale), Adverse Event (AE) or Serious Adverse Event (SAE)
Measured: Baseline of treatment period, 1 month, 2 months,
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2025
- Study start20 Jun 2025 (estimated)
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive Disorder (MDD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xinyu Zhou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xinyu Zhou, First Affiliated Hospital of Chongqing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07011693
- Sponsor's protocol ID
- 1stChongqingCQMU
- Acronym
- SMART-I
- Status last verified
- Jun 2025
- First submitted
- 26 May 2025
- Last updated
- 10 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I): An Open-Label, Multicenter, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07011693
- Acronym / sponsor ID
- SMART-I / 1stChongqingCQMU
- Conditions
- Major Depressive Disorder (MDD)
- Keywords
- adolescent, SSRI, depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Xinyu ZhouUniversity, hospital or other
- Study start
- 20 Jun 2025 (estimated)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 10 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group1-sertraline | Experimental | Drug: Sertralinedosage form: po dosage:25-200mg frequency:qd duration: patients will be given sertraline as a switching treatment to SSRI. |
| Group 2-agomelatine | Experimental | Drug: Agomelatinedosage 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 | Experimental | Drug: Aripiprazoledosage form: po dosage: 1.25-15mg frequency:qn duration: patientswill be given aripiprazole as an add-on treatment to original SSRI. |
Who may qualify
- Ages
- 12 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Aged 12-17;
- As assessed by K-SADS-PL, it meets the DSM-5 criteria for MDD;
- CDRS-R≥45;
- CGI-S≥4;
- 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.
Key exclusion criteria (11 listed)
- Current or lifetime diagnosis of bipolar disorder, schizophrenia, autism, attention-deficit/hyperactivity disorder or obsessive-compulsive disorder or psychosis not otherwise specified;
- MDD with psychotic symptoms;
- YMRS>13;
- Current or lifetime diagnosis of serious neurologic diseases such as epilepsy, brain trauma or other serious physical illnesses;
- 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);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SertralineCommonly used oral antipsychotics intervention therapy. | Drug | Group1-sertraline |
| AgomelatineCommonly used oral antipsychotics intervention therapy. | Drug | Group 2-agomelatine |
| AripiprazoleCommonly used oral antipsychotics intervention therapy. | Drug | Group 3-aripiprazole with original SSRI |
Primary outcome
response rate of Children's Depression Rating Scale (CDRS-R) scores
Time frame: 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.
4 secondary outcomes
Change in Baker Depression Scale（BDI-II) scores from baseline
Time frame: Baseline of treatment period, 4 weeks, 8 weeks
Change in The Screen for Child Anxiety-Related Emotional Disorders (SCARED) scores from baseline
Time frame: Baseline of treatment period, 4 weeks，8 weeks
Change in CGI-S (Clinical Global Impressions-Severity Scales) scores from baseline
Time frame: Baseline of treatment period, 4 weeks, 8 weeks,
Adverse Event (AE) or Serious Adverse Event (SAE)
Time frame: Baseline of treatment period, 1 month, 2 months,
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sertraline, Agomelatine and Aripiprazole in people with Major Depressive Disorder (MDD), run by Xinyu Zhou at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 10 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xinyu Zhou (2912-89012912, zhouxinyu@cqmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
response rate of Children's Depression Rating Scale (CDRS-R) scores (time frame: Baseline of treatment period, 4 weeks, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2025.