Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD)

Study Overview
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Brief Summary
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This project aims to investigate the effectiveness of existing common antidepressants and to provide new evidence for depressed children and adolescents who are not responding to their first treatment.

Detailed Description
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This is an open-label Sequential Multiple Assignment Randomized Trial (SMART) of 16 weeks duration with two levels, each stage 8 weeks. In phase 1, adolescents with MDD will be selected into fluoxetine or fluoxetine combination CBT therapy groups and the choice of treatment will be at the discretion of the patient. Subjects who fail to respond will enter phase 2 randomization， where patients will be randomly assigned to oral sertraline, votioxetine, duloxetine or adding one of aripiprazole, lithium carbonate, and olanzapine to fluoxetine. The primary outcome of the treatment phase is the treatment remission rate and response rate. Secondary outcomes included: symptom scale; Quality of life; Sleep therapy; Symptoms of anxiety; Rumination and safety assessment.

Official Title
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Sequenced Treatment Alternatives to Relieve Adolescent Depression (STAR-AD) a Multicentre Open-label Randomized Controlled Trial Protocol

Conditions
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Depression, Sequestra

Intervention / Treatment
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* Drug: Fluoxetine
* Drug: Sertraline
* Drug: Vortioxetine
* Drug: Duloxetine
* Drug: Aripiprazole
* Drug: Lithium Carbonate
* Drug: Olanzapine
* Behavioral: GCBT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 13 - 18 As assessed by K-SADS-PL, it meets the DSM-V criteria for MDD with non-psychotic symptoms Score≥40 on the CDRS-R Participants with suicidal ideation are eligible, as long as clinicians consider outpatient treatment to be safe Sufficient audio-visual level to complete this study Written informed consent was obtained from patients and at least one of their parents Exclusion Criteria: History of bipolar disorder, schizophrenia, autism, eating disorders, primary obsessive compulsive disorder, pervasive developmental disorder, or psychosis not otherwise specified History of serious physical illnesses Substance abuse or dependence Current depressive episode with clear suicidal plans or suicidal behavior Requires inpatient treatment for psychiatric disorders Severe mental disorders requiring 2 or more failed trials of antidepressant drugs: each trial for at least 8 weeks, with the last 4 weeks at full dose (e.g. fluoxetine 40mg/d, citalopram 40mg/d, escitalopram 20mg/d, sertraline 150mg/d ) History of clear-cut intolerability of, or lack of effect with, an adequate trial of at least one protocol treatment option Taking any medicine that contraindicates in combination with or interferes with the efficacy of the treatment Taking or administering antidepressants within 5 half-lives Received modified electroconvulsive therapy within 12 months If female, is pregnant

Ages Eligible for Study
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Minimum Age: 13 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: After receiving fluoxetine and fluoxetine combined with cognitive-behavioral therapy, the next stage of treatment is determined by the patient's response (remission and non-remission) and is scheduled according to the patient's wishes and random assignment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluoxetine<br>Dosage form: po Dosage: 10-60mg Frequency: qn Course of treatment: 8 weeks. At week 8, patients will be evaluated as in remission or not in remission. Patients who are not in remission will be randomized to phase II treatment based on the patient's wishes. | Drug: Fluoxetine<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: group cognitive behavioral therapy（GCBT）<br>GCBT was administered in addition to fluoxetine and consisted of 11 sessions for 8 weeks. It lasts 90 to 120 minutes, once or twice a week. At week 8, patients will be evaluated as in remission or not in remission. Patients who are not in remission will be randomized to phase II treatment based on the patient's wishes. | Behavioral: GCBT<br>* Commonly used intervention therapy of psychotherapy.<br>|
| Experimental: Sertraline<br>dosage form: po dosage:25-200mg frequency:qn duration: At Week 8, patients assessed as 'non-remission' will be given Sertraline as a switching treatment to fluoxetine. | Drug: Sertraline<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Votioxetine<br>dosage form: po dosage: 10-20mg frequency:qn duration: At Week 8, patients assessed as 'non-remission' will be given votioxetine as a switching treatment to fluoxetine. | Drug: Vortioxetine<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Duloxetine<br>dosage form: po dosage: 60-120mg frequency: qn duration: At Week 8, patients assessed as 'non-remission' will be given duloxetine as an add-on treatment to fluoxetine. | Drug: Duloxetine<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Aripiprazole<br>dosage form: po dosage: 2.5-15mg frequency:qn duration: At Week 8, patients assessed as 'non-remission' will be given aripiprazole as an add-on treatment to fluoxetine. | Drug: Aripiprazole<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Lithium carbonate<br>dosage form:po dosage: 125-500mg frequency: qn duration: At Week 8, patients assessed as 'non-remission' will be given lithium carbonate as an add-on treatment to fluoxetine. | Drug: Lithium Carbonate<br>* Commonly used oral antipsychotics intervention therapy.<br>|
| Experimental: Olanzapine<br>dosage form:po dosage: 1.25-10mg frequency:qn duration: At Week 8, patients assessed as 'non-rremission' will be given olanzapine as an add-on treatment to fluoxetine. | Drug: Olanzapine<br>* Commonly used oral antipsychotics intervention therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CDRS-R (Children's Depression Rating Scale) scores from baseline | Clinical response (≥ 50% reduction in CDRS-R scores from baseline) | Baseline of treatment period, 2 weeks, 1 month, 2 months, 3 months，4months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in BDI-II (Baker Depression Scale) scores from baseline | Change in BDI-II (Baker Depression Scale) scores from baseline | Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 
| Change in SCARED (The Screen for Child Anxiety-Related Emotional Disorders) scores from baseline | Improvement in anxiety (SCARED minus the scores） | Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 
| Change in suicide risk from baseline on the C-SSRS (Columbia Suicide Severity Rating Scale) | The severity of the suicide risk | Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 
| Change in PSQI (Pittsburgh Sleep Quality Index) scores from baseline | Improvement in sleep status (PSQI minus the scores） | Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 
| Change in PedsQL4.0 (The Pediatric Quality of Life Inventory) scores from baseline | Improvement of children's quality of life（PedsQL4.0 minus the scores) | Baseline of treatment period, 2 month, 4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months | 
| 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） | Baseline of treatment period, 1 month, 2 months, 3 months，4 months. | 
| Change in CGI-I (Clinical Global Impressions-Improvement Scales) scores from baseline | Improvement of clinical general Impression scale（ 7-point scale,7 denoting a very significant deterioration） | The treatment period was 1 month, 2 months, 3 months，4 months. | 
| Change in RSS (Ruminative Responses Scale) | The level of improvement in negative thinking（he higher the total score, the more reflective thinking The more severe it is） | The treatment period was 1 month, 2 months. | 
| Change in HCL-32（Hypomania Symptom Checklist-32） | Assess the patient's hypomanic state | Baseline of treatment period, 1 month, 2 months, 3 months，4 months; The follow-up period was 1 month, 3 months, 6 months and 12 months |