Creatine Shows Mixed Results as Add-On Treatment for Depression
A systematic review published June 30, 2026, in Brain Medicine found that creatine supplements produced inconsistent results across five randomized controlled trials involving 238 participants with depression. Two trials showed significant benefits, while three found no meaningful effect.
Creatine supplements may help some people with depression, but the evidence is too mixed to change clinical practice, according to a systematic review published June 30, 2026, in the journal Brain Medicine.
Researchers at the University of Ottawa analyzed six reports from five randomized controlled trials involving 238 participants in South Korea, the United States, Brazil, Israel, and India.
Two trials showed clear benefits. In one, women with major depressive disorder who took 5 grams of creatine daily alongside the antidepressant escitalopram had greater symptom reduction than those on a placebo, with a Cohen's d effect size of 1.13 and higher remission rates. A second trial found that pairing creatine with cognitive behavioral therapy led to a steeper decline in depressive symptoms than therapy alone.
Three other trials found no meaningful benefit. One showed no effect at 5 or 10 grams daily in patients who had not responded to medication. Another found no difference in adolescent girls. A third, focused on bipolar disorder patients in a depressive episode, also showed no improvement.
The bipolar trial raised a safety concern. Two participants developed mania or hypomania after taking creatine, suggesting the supplement may carry risks for people with certain psychiatric diagnoses.
Lead researchers Bassam Jeryous Fares and Nicholas Fabiano said the signal is "interesting" but not a "verdict." They called for larger, longer-term trials that examine different dosages and whether gender affects outcomes, as animal studies suggest creatine may influence depression differently in males and females.
