Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression
Worth asking your prescriber, if a first antidepressant did not work, why venlafaxine over another switch option — the largest trial found roughly one in four remit on any of the three switches tested.
Top of the evidence hierarchy, independently funded. how we score evidence
Caveat on this rating: Later independent reanalyses of the broader STAR*D program have argued its published cumulative remission rates were inflated by protocol deviations; the level-2 switch comparison itself found no significant between-drug differences.
In the NIMH-funded STAR*D trial, 727 patients whose depression had not remitted on citalopram were randomized to a switch; extended-release venlafaxine produced remission in about 25% (24.8% on HRSD-17), which was not statistically better than sertraline or bupropion-SR.
Worth asking
Worth asking your prescriber, if a first antidepressant did not work, why venlafaxine over another switch option — the largest trial found roughly one in four remit on any of the three switches tested.
What it is FDA approved for
Read off the label. Trial duration and approval year are shown only where they were recorded — never inferred.
- Major depressive disorder
- Generalized anxiety disorder (extended-release only)
- Social anxiety disorder (extended-release only)
- Panic disorder (extended-release only)
Source
Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression — Rush AJ, et al. (2006)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1056/NEJMoa052963
DOI: 10.1056/NEJMoa052963
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 727
- Preregistered
- Yes
- Conflicts disclosed
- No
- Independent of proponent
- Yes
- Retracted
- No
Read the full scoring rubric, including what it can't tell you.
Published August 19, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "gold standard". Top of the evidence hierarchy, independently funded. It scores 87 out of 100 on our published rubric. One caveat travels with that badge: Later independent reanalyses of the broader STAR*D program have argued its published cumulative remission rates were inflated by protocol deviations; the level-2 switch comparison itself found no significant between-drug differences. The score is calculated from recorded facts about the source — study design, funding, publication venue, sample size, preregistration — not typed in by an editor.
What is the source for this?
Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression — Rush AJ, et al. (2006). Published in: Top-tier peer-reviewed journal. DOI: 10.1056/NEJMoa052963. The full source is linked on this page so you can read it yourself.
Who paid for this research, and does that matter?
Study design: Randomised controlled trial. Funding: Independently funded. The researchers were independent of whoever benefits from the result. Industry sponsorship is one of the most reliably measured biases in medicine, which is why funding carries real weight in the score rather than sitting in a footnote.
Is venlafaxine (Effexor), effexor FDA approved?
Yes — FDA approved for Major depressive disorder, Generalized anxiety disorder (extended-release only), Social anxiety disorder (extended-release only), Panic disorder (extended-release only). Approval is for a specific indication, not for everything the drug is prescribed for.
Is this medical advice?
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.
This is information to bring to your prescriber, not medical advice and not a reason to change anything on your own. Nothing here is an instruction to stop or reduce a medication. If you are in crisis, call or text 988.