A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to…
The main creatine trial studied 52 women adding it to an SSRI — if I'm already on an antidepressant that's only partly working, how does creatine compare to the augmentation strategies you'd normally use?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: The disclosure statement records that the senior author, Dr Renshaw, "is also an inventor on related patent applications assigned to McLean Hospital and the University of Utah" — an intellectual-property interest in the intervention being tested, which is why independence is marked false here even though the funding is public. The trial was women-only, single-country, and n=52; a later trial in female adolescents found no difference from placebo.
Creatine monohydrate is sold in the US as a dietary supplement under DSHEA, marketed overwhelmingly for exercise performance and muscle mass.
52 South Korean women with major depression all received escitalopram and were randomised to add creatine 5 g/day (n=25) or placebo (n=27) for eight weeks. The creatine group improved significantly more on the Hamilton Depression Rating Scale from week 2 onward, with the advantage maintained at weeks 4 and 8; dropout (32.0% versus 18.5%) and total adverse events (36 versus 45) did not differ. This is the trial the whole creatine-for-depression case is built on, and it enrolled 52 women at one site and has never been directly replicated.
Worth asking
The main creatine trial studied 52 women adding it to an SSRI — if I'm already on an antidepressant that's only partly working, how does creatine compare to the augmentation strategies you'd normally use?
Source
A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. — Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. (2012)
Top-tier peer-reviewed journal
Read the source: https://doi.org/10.1176/appi.ajp.2012.12010009
DOI: 10.1176/appi.ajp.2012.12010009
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Independently funded
- Published in
- Top-tier peer-reviewed journal
- Sample size
- 52
- Preregistered
- Yes
- Conflicts disclosed
- Yes
- Independent of proponent
- No
- 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 "strong evidence". Well-supported by good-quality research. It scores 77 out of 100 on our published rubric. One caveat travels with that badge: The disclosure statement records that the senior author, Dr Renshaw, "is also an inventor on related patent applications assigned to McLean Hospital and the University of Utah" — an intellectual-property interest in the intervention being tested, which is why independence is marked false here even though the funding is public. The trial was women-only, single-country, and n=52; a later trial in female adolescents found no difference from placebo. 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?
A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. — Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. (2012). Published in: Top-tier peer-reviewed journal. DOI: 10.1176/appi.ajp.2012.12010009. 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 not 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 creatine, creatine monohydrate, crm, creapure, creatine hcl, creatine ethyl ester FDA approved for this use?
No. Its current status is: Not FDA-evaluated for this use. Creatine monohydrate is sold in the US as a dietary supplement under DSHEA, marketed overwhelmingly for exercise performance and muscle mass.
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.