Creatine Shows Promise as Add-On Treatment for Depression in New Review

A systematic review published June 30, 2026, in the journal Brain Medicine found that creatine supplements may help reduce depression symptoms when used alongside existing treatments.

Researchers at the University of Ottawa analyzed five randomized clinical trials involving 238 participants. The results were mixed but pointed toward cautious optimism.

Two trials, both focused on women with major depressive disorder, reported significant improvements when creatine was added to treatments such as the antidepressant escitalopram or cognitive behavioral therapy. In one trial, participants taking 5 grams of creatine daily showed greater symptom reduction and higher remission rates than the placebo group.

Three other studies found no meaningful benefit. These included a trial on adolescent girls, a study on patients with treatment-resistant depression, and a trial involving people with bipolar disorder.

The bipolar disorder finding raised a safety concern. Two participants in that trial developed hypomania or mania after taking creatine, suggesting the supplement may affect people differently depending on their underlying psychiatric condition.

For the general population, creatine has a strong safety profile, with only minor gastrointestinal discomfort reported in some cases.

Psychiatrists who reviewed the findings said creatine should not be considered a stand-alone treatment for depression. Patients are advised to consult a healthcare provider before adding it to their regimen, particularly those with kidney disease or who are taking prescribed medications.

The review's authors noted that the current evidence is limited by small sample sizes, a predominance of female participants, and inconsistencies in trial design. They called for larger, longer-term studies.