Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive…

The one trial comparing 5-HTP to an antidepressant had 60 people finish and no placebo group — is that enough for you to consider it a real alternative to an SSRI?

moderate evidence57/100

Reasonable evidence with real limitations. how we score evidence

Caveat on this rating: No placebo arm and no power calculation for equivalence: a trial in which both arms improve and neither wins cannot distinguish "both work" from "neither works and people recovered anyway", and 60 completers is far too few to establish non-inferiority. A single-centre trial that has not been replicated.

Not FDA approved for this useNot FDA-evaluated for this use5-htp5-hydroxytryptophanl-5-htpoxitriptangriffonia simplicifolia extract

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.

Seventy Indian patients in a first depressive episode were randomised to L-5-HTP or fluoxetine for eight weeks; 60 completed. Both groups improved on the Hamilton Depression Rating Scale from week two onward with no meaningful difference between them — 73.3% responded on 5-HTP versus 80% on fluoxetine — and the authors concluded the two were comparable. There was no placebo arm, so the trial shows only that the two treatments moved together, not that either beat the natural course of a first episode.

Worth asking

The one trial comparing 5-HTP to an antidepressant had 60 people finish and no placebo group — is that enough for you to consider it a real alternative to an SSRI?

Source

Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. — Jangid P, Malik P, Singh P, Sharma M, Gulia AK. (2013)

Reputable peer-reviewed journal

Read the source: https://doi.org/10.1016/j.ajp.2012.05.011

DOI: 10.1016/j.ajp.2012.05.011

How this was scored

Study design
Randomised controlled trial
Funding
Funding not disclosed
Published in
Reputable peer-reviewed journal
Sample size
60
Preregistered
No
Conflicts disclosed
No
Independent of proponent
not recorded
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 "moderate evidence". Reasonable evidence with real limitations. It scores 57 out of 100 on our published rubric. One caveat travels with that badge: No placebo arm and no power calculation for equivalence: a trial in which both arms improve and neither wins cannot distinguish "both work" from "neither works and people recovered anyway", and 60 completers is far too few to establish non-inferiority. A single-centre trial that has not been replicated. 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 study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. — Jangid P, Malik P, Singh P, Sharma M, Gulia AK. (2013). Published in: Reputable peer-reviewed journal. DOI: 10.1016/j.ajp.2012.05.011. 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: Funding not disclosed. Independence from the proponent is not recorded. 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.