This Month in Psychopharmacology

STAR-D For Adolescents?

Major depressive disorder (MDD) among adolescents carries high morbidity and rising mortality from suicide and self-harm. However optimal treatment strategies remain unclear, especially for the patients unresponsive to first-line agents.

A study protocol recently published in BMC Psychiatry aims to investigate the comparative effectiveness of first-line treatments for adolescent MDD and subsequent treatment adjustment strategies for those not responding initially..

First-line Treatments.

The first phase of this Sequential Multiple Assignment Randomized Trial (SMART) study will compare fluoxetine monotherapy to combination treatment with fluoxetine plus cognitive behavioral therapy (CBT). Patients will self-select into each arm for the 8-week initial treatment period. Fluoxetine is a first-line SSRI antidepressant for adolescent MDD; CBT also shows efficacy in this population. Comparing monotherapy to combined fluoxetine-CBT should clarify which approach leads to higher response rates.

Managing Non-Responders

For participants not responding at 8 weeks, the study’s second phase will explore various treatment adjustments by randomizing non-responders to additional pharmacotherapy or medication changes. Specifically, non-responders either will augment fluoxetine with aripiprazole, olanzapine, or lithium, or will switch from fluoxetine to sertraline, vortioxetine, or duloxetine for another 8 weeks..

Outcomes Assessment

The primary outcome will be response rates as measured by the Children’s Depression Rating Scale-Revised (CDRS-R). Secondary outcomes will include changes on the Beck Depression Inventory (BDI), the Screen for Child Anxiety-Related Emotional Disorders (SCARED) and the Safe Assessment. The study also will evaluate longer-term sustainability of treatment effects during participants’ subsequent naturalistic care..


This SMART trial design will emulate real-world decision points, providing data to guide best first-line adolescent MDD treatment and prescribe appropriate adjustments when patients do not respond early on. The results will aim to aid clinicians in evidence-based decision-making for this vulnerable population requiring expert care.


He Y. et al. BMC Psychiatry. 2023;23(1):789. Abstract

For more information:


Encore Presentation
12-Year-Old Youth With Depressed Mood and Non-Suicidal Self-Injurious Behavior
CME/CE Credit: 0.50  |  Expires: August 15, 2026


Encore Presentation
Identification and Treatment of the Self-Harming and Suicidal Adolescent
CME/CE Credit: 1.00  |  Expires: November 2, 2025