This work may not be copied, distributed, displayed, published, reproduced, transmitted, modified, posted, sold, licensed, or used for commercial purposes. By downloading this file, you are agreeing to the publisher’s Terms & Conditions.

Original Research

What to Expect When Switching to a Second Antidepressant Medication Following an Ineffective Initial SSRI: A Report From the Randomized Clinical STAR*D Study

A. John Rush, MDa,b,c; Charles South, PhDd,e; Manish K. Jha, MBBSd,f Shailesh Bobby Jain, MDb; and Madhukar H. Trivedi, MDd,*

Published: August 11, 2020

Article Abstract

Objective: An antidepressant medication switch often follows a failed initial trial with selective serotonin reuptake inhibitors (SSRIs). When, for whom, and how often second-step response and remission occur are unclear, as is preferred second-step trial duration. As more treatments are approved for use following 2 failed “adequate” trials, researchers and clinicians require an evidence-based definition of “adequate.”

Methods: Following citalopram in the randomized Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial (which ran July 2001-September 2006), participants with score ≥ 11 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR16) were randomized to bupropion sustained release, sertraline, or venlafaxine extended release (up to 14 weeks). The QIDS-SR16 defined response, remission, and no clinically meaningful benefit based on the modified intent-to-treat sample.

Results: About 80% of 438 participants completed ≥ 6 weeks of treatment with the switch medication. All treatments had comparable outcomes. Overall, 21% (91/438) remitted, 9% (40/438) responded without remission, and 58% (255/438) had no meaningful benefit. Half of the responses and two-thirds of remissions occurred after 6 weeks of treatment. Overall, 33% of responses (43/131) occurred after ≥ 9 weeks of treatment. No baseline features differentiated early from later responders or remitters. No early triage point was found, but those with at least 20% reduction from baseline in QIDS-SR16 score around week 2 were 6 times more likely to respond or remit than those without this reduction.

Conclusions: Following nonefficacy with an initial SSRI, only about 20% remit and more than half achieve no meaningful benefit with a second-step switch to another monoaminergic antidepressant. A 12-week trial duration seems necessary to capture as many second-step switch responders as possible.

Trial Registration: identifier: NCT00021528

Volume: 81

Quick Links:

Continue Reading…

Subscribe to read the entire article


Buy this Article as a PDF