Adjunctive Creatine Treatment for Adolescent Females with Major Depressive Disorder who are Non-Responders to Fluoxetine or Escitalopram

This is an open-label clinical trial of the investigational drug creatine, for augmentation treatment of female adolescents with Major Depressive Disorder (MDD) who have failed to respond to first-line treatment with the SSRIs Fluoxetine or Escitalopram. Widely used by high school and college athletes in the U.S., creatine is an over-the-counter nutritional supplement with annual sales of more than $200 million. Studies in animals show that creatine improves the performance of female rats in the Porsolt Forced Swim test, which is used to predict the efficacy antidepressant compounds. Human neuroimaging studies indicate that patients with MDD have abnormal levels of high-energy phosphate metabolites in brain, primarily adenosine triphosphate (ATP) and phosphocreatine. Research has also shown that creatine supplementation induces changes in these high-energy phosphate metabolites that are associated with a positive response to antidepressants. For the proposed study, twenty female adolescents between the ages of 13-18 with MDD will be recruited for participation in an open-label trial of creatine. Participants with depression will have unremitted MDD despite treatment with Fluoxetine at a dose > 40mg daily for > 4 weeks or Escitalopram at a dose of > 20mg daily for > 4 weeks. Depressed participants will be treated with oral creatine 4gm daily for eight weeks, and will continue to take Fluoxetine or Escitalopram as prescribed.