Creatine yields mixed results in depression trials

A systematic review of existing clinical trials suggests the popular muscle-building supplement creatine may have potential as a treatment for depression, but the evidence remains mixed and inconclusive. The review, published in the journal Brain Medicine on June 30, 2026, analyzed five randomized controlled trials involving 238 participants with major depressive disorder or bipolar disorder.

Researchers from the University of Ottawa led the analysis, which found a split in outcomes. Two trials, both involving women with major depressive disorder, reported benefits. In one study, adding five grams of creatine daily to the antidepressant escitalopram led to greater symptom improvement after eight weeks compared to the antidepressant alone, with a statistically large effect size and more participants reaching remission. A separate trial found that pairing creatine with cognitive behavioral therapy produced a steeper reduction in symptoms than therapy with a placebo.

However, the remaining three trials showed no meaningful benefit. These studies included people with treatment-resistant depression, adolescent girls, and individuals with bipolar disorder experiencing a depressive...