Creatine and Depression: One Small Trial, and the Larger Evidence Around It
Creatine is filed in most people's heads under gym supplement, somewhere between whey protein and pre-workout. It has also been showing up in psychiatric trials since at least 2012. A pilot study from that literature is a useful one to read closely, because what it shows is narrower than the headline.
What the eight-week creatine trial found
An eight-week pilot trial published in European Neuropsychopharmacology randomly assigned 100 adults with depression to receive either creatine monohydrate alongside cognitive behavioral therapy, or a placebo alongside the same therapy [1]. Neither the participants nor the researchers knew who got which. The trial ran in an under-resourced region of India, where access to psychiatric medication is limited, which is part of why the team studied an inexpensive, widely available nutraceutical in the first place.
Participants averaged 30 years old, half were women, and baseline depression scores averaged about 18 on the PHQ-9, a nine-question screener that runs from 0 to 27. Eighteen is in the moderately severe range.
Both groups improved over the eight weeks, which is what you'd expect from CBT on its own. The creatine group improved by about five points more on that 27-point scale. Dropout rates, side effects, and adverse events came out similar between the two arms.
The authors describe this as hypothesis-generating, and they're right to. One hundred people over eight weeks is a pilot study. It was built to test whether a bigger trial is feasible, and the authors call for longer and larger ones.
What other creatine trials have found
This trial is one of several. A systematic review published in January 2026 gathered every randomized controlled trial of creatine monohydrate in psychiatric conditions and found five, covering 238 people between them [2]. That is a very small number of trials. Four studied major depressive disorder, one studied bipolar depression, and no other mental health condition has been tested in a randomized trial.
The results inside those five are uneven. Creatine added to escitalopram, an SSRI antidepressant, outperformed the same SSRI with placebo in 52 women with major depression, and the separation showed up as early as week two [3]. Creatine added to CBT outperformed CBT with placebo, which is the trial above. Creatine added to medication in female adolescents showed no difference from placebo. And creatine added to medication for bipolar depression missed its primary outcome entirely, with no significant difference in depression scores at six weeks [4]. That last trial did find more people reaching remission in the creatine group, though that was a secondary measure in a study of 35 people, and it should be treated as a hint rather than a result.
Observational data adds to this. A 2020 analysis of 22,692 US adults found depression in about 10 out of every 100 people in the lowest quarter of dietary creatine intake, compared with about 6 out of 100 in the highest quarter [5]. After adjusting for income, education, medication use, activity, and other factors, higher dietary creatine intake was associated with roughly a third lower odds of depression, with the strongest signal in women and in adults under 40. This is cross-sectional data, so it can't establish which came first. Depression changes how people eat.
What low creatine intake can tell me about a patient
Two things about this line of research fit how I think about chronic illness.
The first is where creatine comes from. Your body makes some of it, and you eat the rest, mostly in meat and fish. The 2020 analysis measured food intake rather than supplements. Somebody eating very little creatine is usually somebody eating very little animal protein, or very little of anything at all, and both of those tell me something useful about a patient who's depressed.
The second is the proposed mechanism, which involves energy supply rather than serotonin. Creatine's job in the body is to buffer ATP, the usable energy currency inside every cell, and the brain is among the most energy-hungry organs you have. Two of the five trials in that review measured brain phosphocreatine and found that changes in it corresponded to how much people improved [2].
Thinking about it that way is useful in my practice. The patients who describe their low mood as flat and depleted rather than sad often turn out to have an underlying metabolic cause: poor sleep, thyroid, iron, B12, post-viral fatigue. Depression that presents as an energy problem may respond to energy-directed work. Creatine is one candidate for that, and an inexpensive one.
Five small trials is very little evidence for any of that, though, and I'd want considerably more trials before relying on it.
Should you try creatine for low mood?
Creatine monohydrate is among the better-studied supplements on the market for physical performance, and it was generally well tolerated across the psychiatric trials so far. That's the reassuring part.
There is one safety signal. In the bipolar depression trial, two of the 17 people taking creatine switched into hypomania or mania early in the study [4]. The authors of the 2026 review identified those same two cases as the principal safety concern across the whole body of evidence [2]. If you have a bipolar diagnosis, or a family history of one, this is not a supplement to start on your own.
Across the trials, doses ranged from 2 to 10 grams a day over four to eight weeks [2]. I'm describing what researchers tested, not recommending a dose. Whether you should take anything, how much, and how it would interact with what you're already on are questions for the clinician managing your care.
Every positive trial here had one thing in common: creatine was added to something else, an SSRI in one trial and CBT in another. No trial here tested creatine as a standalone treatment for depression, and no trial here supports using it that way.
On the food side, if your protein intake has dropped, then that is reasonable to look at regardless of what future creatine research finds. Appetite loss is a symptom of depression, and poor intake can deepen the fatigue that comes with it.
References
Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. 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. Eur Neuropsychopharmacol. 2024;90:28-35. PMID: 39488067. DOI: 10.1016/j.euroneuro.2024.10.004
Jeryous Fares B, Zhou C, Fabiano N, Wong S, Stubbs B, Shorr R, Puder D, Candow DG, Ostojic SM, Solmi M. The Effect of Creatine Monohydrate on Mental Disorders: A Systematic Review of Randomized Controlled Trials. Can J Psychiatry. 2026. PMID: 41558805. DOI: 10.1177/07067437251408171
Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. 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. Am J Psychiatry. 2012;169(9):937-945. PMID: 22864465. DOI: 10.1176/appi.ajp.2012.12010009
Toniolo RA, Silva M, Fernandes FBF, Amaral JAMS, Dias RDS, Lafer B. A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression. J Neural Transm (Vienna). 2018;125(2):247-257. PMID: 29177955. DOI: 10.1007/s00702-017-1817-5
Bakian AV, Huber RS, Scholl L, Renshaw PF, Kondo D. Dietary creatine intake and depression risk among U.S. adults. Transl Psychiatry. 2020;10(1):52. PMID: 32066709. DOI: 10.1038/s41398-020-0741-x
This article is educational and is not medical advice. It doesn't replace working with a clinician who knows your full history. Nothing here is a recommendation to start, stop, or change any supplement or medication, and depression is a condition that deserves individualized care. If you're struggling, please talk to a licensed provider.
If this resonates with what you're experiencing and you'd like to explore a naturopathic approach, book a consultation with our clinic.
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