A systematic review published in Brain Medicine is drawing attention to creatine as a possible treatment for depression, while underscoring that the evidence remains inconclusive. Researchers led by Bassam Jeryous Fares of the University of Ottawa examined five randomized controlled trials involving 238 participants and found a split result: two studies reported symptom improvement, while three found no meaningful benefit. The authors said the findings are promising enough to justify further research, but not strong enough to change clinical practice.
The trials were conducted in South Korea, the United States, Brazil, Israel and India, with 126 participants receiving creatine and 112 receiving placebo. Most participants were women, with an average age of 36. Four studies focused on major depressive disorder, while one involved people with bipolar disorder during a depressive episode. Because the studies differed substantially in design and methods, the researchers did not pool the data into a single meta-analysis and instead reviewed each trial individually.
The most favorable results came from two studies involving women with major depressive disorder. In one, participants taking five grams of creatine daily alongside escitalopram showed greater reductions in depressive symptoms after eight weeks than those taking escitalopram with a placebo, and more participants reached remission. Another study found greater symptom reduction when creatine was added to cognitive behavioral therapy. Researchers say these findings support further investigation into whether creatine's role in cellular energy production could influence brain function and mood, with possible links to dopamine and serotonin also under study.
At the same time, three other trials did not show a meaningful advantage for creatine. One found no improvement among people whose depression had not responded to medication, even at doses of five or ten grams per day. Another showed no benefit in adolescent girls, and a third found no improvement in participants with bipolar disorder. Researchers also flagged a safety concern after two participants with bipolar disorder who received creatine developed hypomania or mania. Nicholas Fabiano of the University of Ottawa said adverse events were otherwise limited mainly to mild gastrointestinal discomfort, but cautioned that it is not yet possible to say reliably whether creatine improves depressive symptoms across broader patient groups.
The review's authors said the existing studies were small, varied in quality and included disproportionately more women than men, limiting how widely the results can be applied. They called for larger and longer trials, including studies beyond eight weeks and research examining different doses and the effects of combining creatine with exercise. For now, creatine remains better established as a sports supplement than as a treatment for depression, with researchers describing the current evidence as intriguing but unproven.