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What to Expect When Switching to a Second Antidepressant Medication Following an Ineffective Initial SSRI: A Report
A John Rush1,2,3, Charles South4,5, Manish K Jha4,6
1Duke-National University of Singapore, Singapore, Singapore.
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:
ClinicalTrials.gov identifier: NCT00021528.
Insights
Switching antidepressants after selective serotonin reuptake inhibitors (SSRIs) yields limited remission rates. A 12-week trial is recommended to maximize response to second-step depression treatments.
Area of Science:
- Psychiatry
- Clinical Psychology
- Pharmacology
Background:
- Selective serotonin reuptake inhibitors (SSRIs) are common first-line treatments for depression.
- Treatment non-response to initial SSRI trials necessitates medication switching.
- Optimal strategies and durations for second-step antidepressant treatment remain unclear.
Purpose of the Study:
- To investigate the efficacy and optimal duration of second-step antidepressant treatments following SSRI failure.
- To define response and remission rates in patients switching to bupropion, sertraline, or venlafaxine.
- To identify predictors of response and remission in a second-step treatment trial.
Main Methods:
- The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial randomized participants with persistent depressive symptoms after citalopram to bupropion, sertraline, or venlafaxine.
- Treatment duration was up to 14 weeks, with outcomes assessed using the Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR₁₆).
- Response was defined as a QIDS-SR₁₆ score reduction, and remission as a score below a certain threshold.
Main Results:
- Approximately 80% of participants completed at least 6 weeks of the second-step treatment.
- Overall remission rates were 21%, with an additional 9% responding without remission.
- Significant response and remission rates were observed after 6 and 9 weeks of treatment, suggesting longer trial durations are beneficial.
Conclusions:
- Second-step antidepressant monotherapy yields limited remission rates (around 20%) after initial SSRI failure.
- A 12-week trial duration appears necessary to capture the majority of second-step treatment responders.
- Early symptom reduction (around week 2) may predict later response, but no definitive early triage point was identified.
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