Research Explores Creatine's Potential Role in Treating Depression

The review included a total of 238 participants, with 126 assigned to creatine and 112 to a placebo, averaging around 36 years of age, with only 26 percent being male. Four of the trials focused on major depressive disorder, while one targeted bipolar depression. Doses of creatine ranged from 2 to 10 grams per day, with trial durations lasting between four and eight weeks. Of these, two trials had a low risk of bias, while three raised methodological concerns. The overall conclusion was stark: two trials indicated benefits, but three did not.

Bassam Jeryous Fares, the first author of a related short paper published in Brain Medicine around June 30, 2026, summarized the findings by stating, "The signal is interesting, but it is not a verdict."

The most notable improvement in remission rates occurred in a 2012 study that enrolled 52 women with major depressive disorder. Those receiving creatine in addition to the antidepressant escitalopram showed lower depression scores, with 52 percent reaching remission compared to 25.9 percent in the placebo group.

Another randomized trial involving 100 participants tested 5 grams of creatine daily alongside cognitive behavioral therapy, finding similar benefits in the creatine group compared to those on placebo. However, neither study concluded that creatine could replace traditional medications or therapies. Nicholas Fabiano, the corresponding author, emphasized that it is premature to assert that creatine helps alleviate depressive symptoms.

Conversely, other trials did not replicate the positive results. A small study involving adults whose depression did not improve with medication found no significant benefits from creatine, regardless of the dosage. Another trial focusing on adolescent girls already on selective serotonin reuptake inhibitors also yielded negative results, as did a bipolar depression trial that demonstrated no significant advantage for participants taking creatine.

Interestingly, the bipolar trial raised safety concerns, noting two cases of hypomania or mania among 17 participants in the creatine group. While these events were documented, causality could not be established due to the small sample size. Participants across trials also reported gastrointestinal symptoms, headaches, weight gain, dizziness, appetite changes, and sleep difficulties. Although creatine is generally well tolerated at regular doses in healthy adults, its psychiatric use introduces unique considerations.

From a regulatory perspective, it's important to note that the Food and Drug Administration does not approve dietary supplements for safety and efficacy in the same manner as prescription drugs, meaning creatine is not FDA-approved for treating depression.

Future research is necessary to determine the efficacy of creatine in treating depression, with a focus on conducting larger and longer trials. Existing studies do not clarify the ideal dosage, whether benefits persist beyond eight weeks, or which patients might benefit the most. Currently, the evidence reflects a significant gender bias, as most participants were women, leaving questions about the broader applicability of the findings across diverse populations in the U.S.

This ongoing dialogue in the scientific community illustrates the contrast between creatine's established reputation in sports nutrition and its still-developing status in mental health research. As studies continue, the question remains: Can larger trials provide compelling evidence for creatine's role in depression treatment?