Two Studies Found Benefits While Three Did NotThe researchers reviewed six published reports covering five randomized controlled trials involving 238 participants from five countries. Another trial found that creatine combined with cognitive behavioral therapy was associated with a greater decline in depressive symptoms than therapy paired with a placebo. Researchers have therefore begun investigating whether changes in the brain's energy metabolism could play a role in mood disorders. The review authors noted that people with depression may have altered creatine metabolism in the brain. "The signal is interesting, but it is not a verdict," Bassam Jeryous Fares said, emphasizing that the findings do not yet establish a direct cause-and-effect relationship between creatine metabolism and depression.