In children and teenagers, only one antidepressant clearly beat placebo
Across 34 trials of 14 antidepressants in under-18s, only fluoxetine was statistically better than placebo - and only just.
Top of the evidence hierarchy, independently funded. how we score evidence
Cipriani, Zhou and colleagues pooled every double-blind trial of antidepressants for major depression in under-18s. They searched regulator websites and trial registers too, to catch unpublished results.
Significant findings
34 trials, 5,260 young people, 14 drugs - and one drug that beat placebo. Fluoxetine's margin nearly touched zero.
Tolerability separated the drugs more than benefit did. Imipramine, venlafaxine and duloxetine all caused more dropouts for side effects than placebo, imipramine at over five times the placebo rate.
The caution runs both ways. Evidence quality was rated very low in most comparisons - small trials, mostly industry-funded, at high or unclear risk of bias.
That makes the negative results about individual drugs almost as uncertain as the positive one. The honest reading is that the evidence here is thin, not that these drugs are known to fail.
This covers acute treatment only, typically eight to twelve weeks. It says nothing about staying on them.
Worth asking
What did we try before this, what exactly are we measuring, and is therapy running alongside?
Never stop or change a prescribed antidepressant on your own. Abrupt stops can be dangerous, and any change needs a prescriber-supervised taper.
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 tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis — Cipriani A, et al. (2016)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1016/S0140-6736(16)30385-3
DOI: 10.1016/S0140-6736(16)30385-3
How this was scored
- Study design
- Meta-analysis of randomised trials
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 5,260
- 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. Last verified August 31, 2026.
Questions
How strong is the evidence behind this?
Resolv rates this source "gold standard". Top of the evidence hierarchy, independently funded. It scores 94 out of 100 on our published rubric. 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 tolerability of antidepressants for major depressive disorder in children and adolescents: a network meta-analysis — Cipriani A, et al. (2016). Published in: Top-tier peer-reviewed journal. DOI: 10.1016/S0140-6736(16)30385-3. 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.