Tryptophan and 5-hydroxytryptophan for depression.
Only two usable trials of 5-HTP for depression exist and they enrolled 64 people between them — is there any reason to bet on that instead of a treatment that has been tested in thousands?
Reasonable evidence with real limitations. how we score evidence
Caveat on this rating: The pooled odds ratio looks impressive but rests on 64 patients with a confidence interval running from 1.28 to 13.15 — statistically positive and practically uninformative. The review is from 2002 and predates almost nothing, because almost nothing usable has been published since.
5-HTP is sold in the US as a dietary supplement under DSHEA. It has never been approved by the FDA to treat depression, anxiety, insomnia, fibromyalgia, or anything else, and no FDA review of safety, purity, or effectiveness precedes it going on sale.
The reviewers located 108 trials of tryptophan or 5-HTP for depression and found that only two of them, involving 64 patients in total, were of sufficient quality to include. Those two favoured the supplements over placebo (Peto odds ratio 4.10, 95% CI 1.28 to 13.15), but the reviewers judged the evidence insufficient to be conclusive and concluded that, because antidepressants proven effective and safe already exist, the clinical usefulness of 5-HTP and tryptophan is limited. This remains the only Cochrane review of 5-HTP for depression and has not been updated in over two decades.
Worth asking
Only two usable trials of 5-HTP for depression exist and they enrolled 64 people between them — is there any reason to bet on that instead of a treatment that has been tested in thousands?
Source
Tryptophan and 5-hydroxytryptophan for depression. — Shaw K, Turner J, Del Mar C. (2002)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1002/14651858.CD003198
DOI: 10.1002/14651858.CD003198
How this was scored
- Study design
- Systematic review of randomised trials
- Funding
- Funding not disclosed
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 64
- Preregistered
- No
- 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.
Where we put this study in context
Questions
How strong is the evidence behind this?
Resolv rates this source "moderate evidence". Reasonable evidence with real limitations. It scores 69 out of 100 on our published rubric. One caveat travels with that badge: The pooled odds ratio looks impressive but rests on 64 patients with a confidence interval running from 1.28 to 13.15 — statistically positive and practically uninformative. The review is from 2002 and predates almost nothing, because almost nothing usable has been published since. 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?
Tryptophan and 5-hydroxytryptophan for depression. — Shaw K, Turner J, Del Mar C. (2002). Published in: Top-tier peer-reviewed journal. DOI: 10.1002/14651858.CD003198. 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: Systematic review of randomised trials. Funding: Funding not disclosed. 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 5-htp, 5-hydroxytryptophan, l-5-htp, oxitriptan, griffonia simplicifolia extract FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. 5-HTP is sold in the US as a dietary supplement under DSHEA. It has never been approved by the FDA to treat depression, anxiety, insomnia, fibromyalgia, or anything else, and no FDA review of safety, purity, or effectiveness precedes it going on sale.
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.