Creatine Depression Review: Mixed Trial Results
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- University of Ottawa researcher Bassam Jeryous Fares led a systematic review published in Brain Medicine on June 30, 2026, covering five randomized controlled trials with 238 total participants—126 on creatine, 112 on placebo
- The trials were conducted in South Korea, the United States, Brazil, Israel, and India, with participants averaging 36 years of age and most being women; two trials enrolled only women
- Two trials in women with major depressive disorder found benefit: one study pairing five grams of daily creatine with the antidepressant escitalopram produced a large symptom reduction (Cohen's d of 1.13) after eight weeks compared with placebo plus escitalopram
- Three trials reported no meaningful benefit—including a study in treatment-resistant depression testing both five- and ten-gram doses, one in adolescent girls, and one in people with bipolar disorder
- Two participants with bipolar disorder developed hypomania or mania while taking creatine, a safety flag beyond the mild gastrointestinal discomfort otherwise noted in the review
- Corresponding author Nicholas Fabiano, a psychiatry resident at the University of Ottawa, said current evidence does not support routine use and called for larger, longer trials extending beyond eight weeks, including studies pairing creatine with exercise
Why it matters: With two positive and three null trials and a documented mania risk in bipolar patients, creatine is not ready for clinical use—but the gender-skewed positive signal and the supplement's wide availability make a strong case for dedicated, larger Phase 3-style trials rather than uncontrolled self-supplementation by patients.
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