For millions of Americans, major depressive disorder is a heavy burden, leading to an overwhelming feeling of exhaustion and an inability to feel pleasure or joy. The disorder is not limited to adults. It's estimated that 2 percent of children and 6 percent of adolescents are affected.
Depression in adolescents can have devastating effects. "The CDC's [Center for Disease Control] Youth Risk Behavior Surveillance System shows that among American ninth to twelfth graders, every year 15.8-percent contemplate suicide, and 7.8-percent actually attempt it," says Douglas Kondo, Assistant Professor of Psychiatry at the University of Utah. While not all at-risk youth have major depressive disorder, at least 40-percent of those who do, are resistant to treatment. "We have to do better," says Kondo.
If scientists can figure out how the brains of depressed patients are different, says Kondo, then they have a better chance of finding treatments that will work. The primary tool that he and co-investigator and USTAR professor Perry Renshaw use to track these chemical changes in the brain is an advanced form of MRI known as magnetic resonance spectroscopy (MRS).
MRS allowed them to literally see that people with depression have lower levels of phosphocreatine, a chemical that serves as an energy reserve in the brain. Levels of phosphocreatine also correlate with how well people respond to treatment. "If you have high levels of phosphocreatine in the brain you are quite likely to get better with treatment, whereas if you have low levels of phosphocreatine you are less likely to respond," says Renshaw.
These results led the researchers to speculate that supplementing the diets of depression patients with creatine, along with their existing treatment, may increase phosphocreatine levels in their brains, and elevate their mood. Unlike the majority of existing treatments for depression, creatine is not a pharmaceutical drug. It is a nutritional supplement that can be found in any health food store. "This is an unusual strategy to use in developing therapies for psychiatric disorders," says Renshaw.
When Renshaw and colleagues initially tested the effects of creatine in lab rats, the results were surprising. "The male rats who got the creatine didn't think much of it one way or another, but the female rats who got the creatine thought it was the most potent anti-depressant they had ever seen," says Renshaw. Female rats that were fed the supplement had less anxiety during testing, as well as more activity than males or untreated females. It is not fully understood why the female rats responded and males did not, but is thought to be due to hormonal differences.
Based on results from the rat studies, Renshaw, Kondo, and their colleagues in South Korea conducted clinical studies in adult women with major depressive disorder. The proof of concept study showed an increase of 5 to 10 percent in phosphocreatine levels in the female brain in as early as two weeks following a relatively low dose of creatine of 5 grams daily.
And their symptoms improved significantly says Renshaw, "the women who got creatine in addition to Lexapro [SSRI antidepressant] got better twice as quickly and twice as much as the women who only got the SSRI."
Renshaw speculates on how creatine works to alleviate depression, "It makes it possible for that initial effect of the drug to be much more potent in the cell by making sure there is not [an] energy barrier that keeps it from having it's beneficial effects." In other words, creatine may prime the cell into being receptive to antidepressant drugs.
Kondo believes that adding creatine to prescribed anti-depressant regiments may be a particularly effective approach for teens with treatment resistant depression. "The standard of care has already been used on this child or young person, this adolescent, and it hasn't been successful," says Kondo. His group is now recruiting females between the ages of 13-21 years old for a study, which will determine the creatine dose that offers not only the best clinical response in conjunction with antidepressant medications, but also changes in brain phosphocreatine levels and has the fewest side effects.
Renshaw says that while they are optimistic about their results so far, it's important to be realistic about the limitations of any single study or first couple of small studies. He says that as for all research, the studies need to be repeated by others.
NOTE: People should not make changes to their medication regiment without first talking to their doctor.
Kim Schuske contributed to this story