Five randomized trials involving 238 participants produced mixed evidence on creatine for depression, with two studies showing added symptom relief and three finding no meaningful benefit.
Two positive trials involved women with major depressive disorder: one paired 5 grams daily with escitalopram for eight weeks and reported larger symptom reductions, while another found benefit alongside cognitive behavioral therapy.
Three other trials showed no advantage over placebo in treatment-resistant depression, adolescent girls, or bipolar depression; two bipolar participants on creatine developed hypomania or mania.
University of Ottawa researchers said the evidence is too limited to change practice because the studies were small, mostly female, and varied in design and bias risk.
The review argues creatine remains a plausible but unproven option, with larger and longer trials needed to test dose, sex differences, and use with exercise.