Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An…
The newest creatine trial added it to therapy rather than to medication — if I'm in therapy, is that a combination worth trying, and how would we tell whether it helped?
Well-supported by good-quality research. how we score evidence
Caveat on this rating: A 5-point PHQ-9 difference is large for a supplement, which is itself a reason for caution in a 100-person pilot that was explicitly powered for feasibility rather than efficacy and was conducted at a single site in a setting where access to other care is limited. No trial registration appears in the PubMed record, so the primary outcome cannot be checked against a pre-specified protocol. It has not been replicated.
Creatine monohydrate is sold in the US as a dietary supplement under DSHEA, marketed overwhelmingly for exercise performance and muscle mass.
100 adults with depression in an under-resourced region of India (mean age 30.4, mean baseline PHQ-9 17.6, half women) were randomised to creatine plus cognitive behavioural therapy or placebo plus CBT for eight weeks. Both arms improved; the creatine arm improved more, by a mean difference of 5.12 points on the PHQ-9. Dropouts and adverse events were comparable between arms. The authors describe it as a pilot, feasibility and hypothesis-generating trial and call for longer and larger studies — their own published follow-up correspondence is titled "Preliminary evidence should be treated as such."
Worth asking
The newest creatine trial added it to therapy rather than to medication — if I'm in therapy, is that a combination worth trying, and how would we tell whether it helped?
Source
Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. — Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. (2025)
Reputable peer-reviewed journal
Read the source: https://doi.org/10.1016/j.euroneuro.2024.10.004
DOI: 10.1016/j.euroneuro.2024.10.004
How this was scored
- Study design
- Randomised controlled trial
- Funding
- Independently funded
- Published in
- Reputable peer-reviewed journal
- Sample size
- 100
- Preregistered
- No
- 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 "strong evidence". Well-supported by good-quality research. It scores 80 out of 100 on our published rubric. One caveat travels with that badge: A 5-point PHQ-9 difference is large for a supplement, which is itself a reason for caution in a 100-person pilot that was explicitly powered for feasibility rather than efficacy and was conducted at a single site in a setting where access to other care is limited. No trial registration appears in the PubMed record, so the primary outcome cannot be checked against a pre-specified protocol. It 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?
Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. — Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. (2025). Published in: Reputable peer-reviewed journal. DOI: 10.1016/j.euroneuro.2024.10.004. 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 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.