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Evevident
Original paper
2006NEJMPsychiatry

STAR*D

Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression

RCTMajor depressive disorder

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Overview

After SSRI failure, switching to another antidepressant produced modest remission with no clear winner.

Clinical takeaway

STAR*D made depression care more practical and measurement-based: reassess, optimize, switch or augment, and set expectations that remission becomes harder after each failed step.

Key result

After citalopram nonremission, remission rates after switching to bupropion-SR, sertraline, or venlafaxine-XR were similar.

Practice impact

Depression treatment became framed as sequenced, measurement-based care rather than one-shot SSRI prescribing.

Evidence

Study design

Large pragmatic randomized effectiveness trial within a sequenced depression-treatment program.

Enrollment

727

Follow-up

Up to 14 weeks for the level-2 switch comparison.

Geography

United States

Clinical question

After unsuccessful initial SSRI therapy for major depression, is switching to bupropion-SR, sertraline, or venlafaxine-XR more effective?

Population

  • Adults with nonpsychotic major depressive disorder who did not remit or could not tolerate initial citalopram therapy.

Intervention

Switch to bupropion-SR, sertraline, or venlafaxine-XR.

Comparator

Active antidepressant switch strategies compared with each other.

Primary outcome

Remission of depressive symptoms.

Switching to bupropion-SR, sertraline, or venlafaxine-XR yielded similar remission rates after initial SSRI failure.

Between-group comparison / p=no significant difference

Key results

  • Remission rates were similar among bupropion-SR, sertraline, and venlafaxine-XR switch strategies.
  • No medication clearly dominated after initial SSRI failure.
  • Across STAR*D steps, cumulative remission increased but relapse and dropout were common.

Harms

  • Adverse effects differed by antidepressant and influenced tolerability.
  • Activation, sexual dysfunction, blood pressure effects, and drug interactions should guide medication choice.

Clinical Use

When to cite

  • When planning next steps after a patient does not remit on an initial SSRI.

Practice impact

  • Popularized measurement-based, sequenced treatment for major depressive disorder.

Applicability

  • Primary-care and psychiatry patients with major depression who do not remit after an adequate first antidepressant trial.

Limitations

  • Open-label pragmatic design and complex multi-step program.
  • STAR*D has been debated for outcome definitions and analytic choices.

Common misinterpretations

  • Do not say STAR*D proved all antidepressants are equivalent; it showed no clear winner among these switch options after initial SSRI failure.

Related evidence

CATIE - Context

Citation

Rush AJ, Trivedi MH, Wisniewski SR, et al. Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression. N Engl J Med. 2006;354(12):1231-1242. doi:10.1056/NEJMoa052963

After unsuccessful treatment with an SSRI, approximately one in four patients had a remission of symptoms after switching to another antidepressant.