Creatine monohydrate. The review is about a dose of this, taken alongside treatment rather than instead of it.
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Illustrative. Not a product named in the review.
Creatine Might Help With Depression, But Only in a Specific Group So Far
Creatine has spent years building a reputation well beyond the gym, with people trying it for cognition, energy, and now mood. A new systematic review pulled together every randomized trial testing creatine specifically for depression symptoms, and the honest answer it landed on is maybe, in a specific group, not yet a clear yes.
- A new systematic review pooled five clinical trials of creatine for depression, totaling 238 participants, and found genuinely mixed results.
- Two trials found real benefit, both in adult women taking creatine alongside standard antidepressant treatment, not as a stand alone fix.
- Three trials, including one in treatment resistant patients and one in adolescent girls, found no benefit at all.
- Two participants in the underlying trials developed hypomania or mania, a real safety note worth knowing about.
Trials found benefit
Both in adult women, and both with creatine added on top of an antidepressant or cognitive behavioral therapy.
Trials found none
Including one in patients whose depression had not responded to prior treatment, and one in adolescent girls.
Five randomised trials, 238 participants in total: 126 on creatine, 112 on placebo, across five countries. Individual trials ran 4 to 10 weeks with 10 to 100 people.
What the researchers actually did
Published in Brain Medicine and led by researchers at the University of Ottawa and the University of Toronto, the review pooled five randomized controlled trials of creatine monohydrate in people with mood disorders, 126 participants on creatine and 112 on placebo, run across South Korea, the United States, Brazil, India, and Israel.
What the evidence actually shows
creatine worked well in one specific setting and flopped in others, in the same body of evidence
Two of the five trials found creatine, added on top of standard treatment, meaningfully reduced depressive symptoms, and both of those were in adult women receiving either an antidepressant or cognitive behavioral therapy alongside the creatine. The other three trials found no clear benefit, including in patients whose depression had not responded to prior treatment and in a trial of adolescent girls. Put plainly, creatine worked well in one specific setting and flopped in others, in the same body of evidence.
Honest caveat
The review's own authors are explicit that this is underpowered evidence. Individual trials ranged from about 10 to 100 participants and lasted only 4 to 10 weeks, most cohorts skewed heavily toward one sex, and the populations tested were different enough from each other that comparing them directly is shaky. Separately, two participants across the underlying trials developed hypomania or mania, a real safety signal, though creatine was otherwise well tolerated with mostly mild digestive side effects. The authors conclude larger, more balanced trials are needed before creatine earns a real place in psychiatric care.
What this means for you
If you already take creatine for muscle or cognition and were curious whether it might help your mood too, this is an honest maybe rather than a hype answer, and the clearest signal so far points to it working best as an add on to standard treatment in women, not as something to try solo. If you have a personal or family history of bipolar disorder or mania, the hypomania signal in these trials is worth bringing up with a doctor before adding creatine on top of any mood medication.
Primary sources
- Fares et al., "Creatine supplementation for treating symptoms of depression: a systematic review and meta analysis," Brain Medicine, June 30, 2026.
- EurekAlert, "Creatine shows promise for depression, but the evidence is not yet settled," June 2026.
Common questions
Should I take creatine to help with depression?
This review is not strong enough to self prescribe on, in the authors' own words. The clearest benefit shown was in women adding creatine to standard antidepressant treatment, not as a stand alone fix, and three of the five trials found no benefit at all.
Is creatine safe to combine with antidepressants?
In these trials it was generally well tolerated with mostly mild digestive side effects. That said, two participants in the underlying trials developed hypomania or mania, so anyone with bipolar disorder or a mood disorder history should treat that as a real safety flag and talk to a doctor first.
Why did creatine work in some trials and not others?
The trials were small, ranged from 4 to 10 weeks, and studied different populations, adult women on standard treatment, treatment resistant patients, and adolescent girls. The review's authors think that mix of short, small, and varied trials is the most likely reason results pulled in different directions, not that creatine reliably works for one group and not another.
Stay Curious.
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