Switching to another antidepressant following SSRI failure appears largely ineffective
Approximately 20% of those with depression who did not respond to an SSRI remitted, and more than half saw no real benefit by switching to another monoaminergic agent, according to study results published in Journal of Clinical Psychiatry.
“While we may not know which medication someone is going to benefit from prior to starting the treatment, we can determine fairly quickly if the treatment is going to work," Madhukar H. Trivedi, MD, of the department of psychiatry at University of Texas Southwestern Medical Center, told Healio Psychiatry. "Studies have shown that we can determine if a treatment is going to work within 2-4 weeks, rather than the previously thought 12 weeks. This is extremely important for individuals with difficult-to-treat depression, who can go for years before finding the right treatment.”
Prior studies compared second-step medication switch outcomes among a large group of representative outpatients included in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had depression without adequate benefit and/or were intolerant to the initial SSRI treatment, citalopram, and thus accepted a medication switch. However, questions remained regarding care delivery among this patient population.
Trivedi and colleagues sought to determine when, for whom and how often second-step response and remission occurred, as well as preferred second-step trial duration. Further, they aimed to provide researchers and clinicians with an evidence-based definition of “adequate” regarding treatments approved for use following two failed adequate trials. STAR*D participants who first received citalopram and had a score of 11 or greater on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR16) were then given bupropion sustained released, sertraline or venlafaxine extended release. The QIDS-SR16 defined remission, response and no clinically meaningful benefit according to the modified intent-to-treat sample.
Results showed 80% of 438 patients completed 6 weeks or more of treatment with the switch medication, and all treatment outcomes were comparable. Among all patients, 91 (21%) remitted, 40 (9%) responded without remission and 255 (58%) had no meaningful benefit. Two-thirds of remissions and half of the responses occurred after 6 weeks of treatment, and 43 (33%) of responses occurred after 9 weeks or more of treatment. The investigators observed no baseline features that differentiated early from later remitters or responders. Moreover, they found no early triage point; however, patients with 20% or greater reduction from baseline in QIDS-SR16 score around 2 weeks were six times more likely to remit or respond vs. those without this reduction.
"If someone isn’t showing significant improvement within 3 months, even if they have difficult-to-treat depression, it’s time to try something new," Trivedi told Healio Psychiatry. "More importantly, it is time for our field to move beyond our current method for selecting treatment and truly develop personalized medicine for people with depression. Months and years of continued depression is way too long, and we need improved methods for selecting the right treatment at the start.”