Women battling stubborn major depression may have a surprising new ally in their fight—the muscle-building dietary supplement creatine.

In a new proof-of-concept study, researchers from three South Korean universities and the University of Utah report that women with major depressive disorder (MDD) who augmented their daily antidepressant with 5 grams of creatine responded twice as fast and experienced remission of the illness at twice the rate of women who took the antidepressant alone. The study, published Aug. 3, 2012, in the American Journal of Psychiatry online, means that taking creatine under a doctor's supervision could provide a relatively inexpensive way for women who haven't responded well to SSRI (selective serotonin reuptake inhibitor) antidepressants to improve their treatment outcomes.

"If we can get people to feel better more quickly, they're more likely to stay with treatment and, ultimately, have better outcomes," says Perry F. Renshaw, M.D., Ph.D., M.B.A, USTAR professor of psychiatry at the University of Utah medical school and senior author on the study.

"There has been a misunderstanding of how crippling and common this disease is in Utah," says Renshaw, who is also medical director of the Mental Illness Research, Education and Clinical Center at the Salt Lake City Veterans Affairs Health Care System. "It begs that we understand it better than we do."

Creatine is an amino acid made in the human liver, kidneys, and pancreas. It also is found in meat and fish. Inside the body it is converted into phosphocreatine and stored in muscle. During high-intensity exercise, phosphocreatine is converted into ATP, an important energy source for cells. For this reason, creatine has become a popular supplement among bodybuilders and athletes who are trying to add muscle mass or improve athletic ability.

How creatine works against depression is not precisely known, but Renshaw and his colleagues suggest that the pro-energetic effect of creatine supplementation, including the making of more phosphocreatine, may contribute to the earlier and greater response to antidepressants.

The eight-week study included 52 South Korean women, ages 19-65, with major depressive disorder. All the women took the antidepressant escitalopram during the trial. Twenty-five of the women received creatine with the escitalopram and 27 were given a placebo. Neither the study participants nor the researchers knew who received creatine or placebo. Eight women in the creatine group and five in the placebo group did not finish the trial, leaving a total of 39 participants.

Participants were interviewed at the start of the trial to establish baselines for their depression, and then were checked at two, four, and eight weeks to see how they'd responded to escitalopram plus creatine or escitalopram and a placebo. The researchers used three measures to check the severity of depression, with the primary outcomes being measured by the Hamilton Depression Rating Scale (HDRS), a widely accepted test.

The group that received creatine showed significantly higher improvement rates on the HDRS at two and four weeks (32 percent and 68 percent) compared to the placebo group (3.7 percent and 29 percent). At the end of eight weeks, half of those in the creatine group showed no signs of depression compared with one-quarter in the placebo group. There were no significant adverse side effects associated with creatine.

Antidepressants typically don't start to work until four to six weeks. But research shows that the sooner an antidepressant begins to work, the better the treatment outcome, and that's why Renshaw and his colleagues are excited about the results of this first study. "Getting people to feel better faster is the Holy Grail of treating depression," he says.

Study co-author Tae-Suk Kim, M.D., Ph.D., associate professor of psychiatry at the Catholic University of Korea College of Medicine and visiting associate professor of psychiatry at the University of Utah, already is recommending creatine for some of his female depression patients.

In prior studies, creatine had been shown to be effective only in female rats. But that shouldn't rule out testing the supplement in men as well, according to Renshaw.

University of Utah researchers expect soon to begin another trial to test creatine in adolescent and college-age females who have not responded to SSRI medications.

The first authors on the study are In Kyoon Loo, M.D., Ph.D., professor of the Seoul National University College of Medicine and College of Natural Sciences, Seoul, South Korea, and USTAR research associate professor of psychiatry at the University of Utah, and Sujung Yoon, M.D., Ph.D., associate professor of psychiatry at the Catholic University of Korea College of Medicine, Seoul, and visiting associate professor of psychiatry at the University of Utah.

Other authors include Jaeuk Hwang M.D., Ph.D., of the Soonchunhyang University College of Medicine, Seoul; Wangyoun Won, M.D., Catholic University of Korea College of Medicine, Seoul; Jieun E. Kim, M.D., Ph.D., Ewha Womans University Graduate School, Seoul; Sujin Bae, Ph.D., Seoul National University College of Natural Sciences.