Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major…
Fluoxetine ranked mid-pack for effect but high for tolerability in this huge comparison - which of those mattered more in choosing it for me?
Top of the evidence hierarchy, independently funded. how we score evidence
Caveat on this rating: Publicly funded (NIHR and Japan Society for the Promotion of Science); some co-authors disclosed lecture or consultancy fees from drug manufacturers.
Across 522 randomised trials with 116,477 adults, fluoxetine beat placebo for major depression and was among the better-tolerated antidepressants, though other drugs ranked higher on effectiveness in head-to-head comparisons.
Worth asking
Fluoxetine ranked mid-pack for effect but high for tolerability in this huge comparison - which of those mattered more in choosing it for me?
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 (acute and maintenance treatment)
- Obsessive-compulsive disorder
- Bulimia nervosa (moderate to severe; binge-eating and vomiting behaviors)
- Panic disorder, with or without agoraphobia
- Depressive episodes associated with bipolar I disorder (in combination with olanzapine)
- Treatment-resistant depression (in combination with olanzapine)
Source
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis — Cipriani A, et al. (2018)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1016/S0140-6736(17)32802-7
DOI: 10.1016/S0140-6736(17)32802-7
How this was scored
- Study design
- Meta-analysis of randomised trials
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 116,477
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- 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 100 out of 100 on our published rubric. One caveat travels with that badge: Publicly funded (NIHR and Japan Society for the Promotion of Science); some co-authors disclosed lecture or consultancy fees from drug manufacturers. 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?
Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis — Cipriani A, et al. (2018). Published in: Top-tier peer-reviewed journal. DOI: 10.1016/S0140-6736(17)32802-7. 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: Meta-analysis of randomised trials. 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 fluoxetine (Prozac, Sarafem), prozac, sarafem FDA approved?
Yes — FDA approved for Major depressive disorder (acute and maintenance treatment), Obsessive-compulsive disorder, Bulimia nervosa (moderate to severe; binge-eating and vomiting behaviors), Panic disorder, with or without agoraphobia, Depressive episodes associated with bipolar I disorder (in combination with olanzapine), Treatment-resistant depression (in combination with olanzapine). 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.