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

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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;
• 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.