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

Launched by XINYU ZHOU · Jun 5, 2025

Keywords

ClinConnect Summary

The SMART-I trial is studying how well common antidepressants work for teenagers aged 12 to 17 who are dealing with major depressive disorder (MDD) but did not improve after their first treatment with a type of medication called SSRIs. This trial aims to find better ways to help these young people by switching their medication or adding new treatments. To join the study, participants must have experienced significant depression symptoms for a certain period and must have tried an SSRI medication like fluoxetine without seeing enough improvement.

The trial is not currently recruiting participants, but it is important for families to know that if a teenager meets the eligibility criteria, they might have the opportunity to try new treatment options. Participants will be closely monitored by healthcare professionals throughout the study to assess their response to the medications and ensure their safety. This research could lead to better treatment strategies for adolescents struggling with depression when initial treatments do not work.

Gender

ALL

Eligibility criteria

• 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.