Creatine Treatment for Female Adolescents With Depression Who Are Non-Responders to Fluoxetine or Escitalopram
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Creatine Monohydrate
Intervention description: Creapure brand of creatine monohydrate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: Female
Minimum age: 13 Years
Maximum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Depression; Females; Adolescents

Summary:

      The purpose of this study is to see if creatine, which is a naturally occurring chemical in
      the body, is effective for treating Major Depressive Disorder (MDD) in female teenagers.
      Creatine may have effects of interest in the brain. The reason for the MRI component of this
      study is to learn about new ways to see inside the brain. The investigators will use magnetic
      fields and radio waves to look at the brain and chemicals in the brain. The investigators
      hope that this technique will have medial use in the future.

      The primary hypothesis of the study is that oral creatine supplementation will have a
      beneficial effect as adjunctive therapy in female adolescents with MDD who are non-responders
      to an adequate trial of the SSRIs Fluoxetine or Escitalopram.
    

Eligibility criteria:

        Inclusion Criteria for Major Depressive Disorder Participants:

          -  Participants must meet DSM-IV-TR criteria for Major Depressive Disorder, with current
             mood state depressed for ≥ 2 weeks.

          -  Participants must be females

          -  Participants must be between the age of 13 and 18 years.

          -  Participants must have had an adequate trial of fluoxetine, defined as a trial of ≥ 8
             weeks of treatment, with a dose of ≥ 40mg daily for ≥ 4 weeks. If the participant had
             a trial of 40mg daily and was unable to tolerate it, a dose of 20mg for ≥ 8 weeks is
             acceptable; OR

          -  Participants must have had an adequate trial of escitalopram, defined as a trial of ≥
             8 weeks of treatment, with a dose of ≥ 20 mg daily for ≥ 4 weeks. If the participant
             had a trial of 20 mg daily and was unable to tolerate it, a dose of 10 mg for ≥ 8
             weeks is acceptable.

          -  Participants must have a CDRS-R score of ≥ 40 and a CGI-S score of ≥ 4.

          -  Participants must be able to give informed consent or assent, and where applicable,
             parent(s)/guardian(s) must be able to give informed permission for study
             participation.

        Inclusion Criteria for Healthy Control Participants:

          -  Participants must be females

          -  Participants must be between the age of 13 and 18 years.

          -  Participants must not meet DSM-IV-TR diagnostic criteria for a psychiatric or
             substance abuse disorder.

          -  Participants must be able to give informed consent or assent and, where applicable,
             parent(s)/guardian(s) must be able to give informed permission for study
             participation.

        Exclusion Criteria for Treatment-Resistant Major Depressive Disorder Participants:

          -  Unstable co-morbid medical, neurological or psychiatric disorder.

          -  Pre-existing renal disease.

          -  Proteinuria or microalbuminuria.

          -  Pregnant females, nursing mothers, or females of childbearing potential who are unable
             or unwilling to practice birth control during the study. Participants who are of
             child-bearing potential must have a negative urine pregnancy test before each MRI/MRS
             brain scan.

          -  High risk for suicidal behavior, homicidal behavior or self-harm.

          -  Adolescents who are unlikely to be able to comply with the study protocol.

          -  DSM-IV-TR criteria for current substance abuse or substance dependence, with the
             exception of nicotine abuse or dependence.

          -  Contraindication to MRI/MRS brain scans, such as ferromagnetic implants or
             claustrophobic anxiety.

          -  Documented or suspected history of intellectual disability (Full-Scale I.Q. < 70).

          -  History of hypersensitivity to creatine monohydrate.

        Exclusion Criteria for Healthy Controls:

          -  Clinically significant psychiatric or substance abuse disorder.

          -  Unstable medical or neurological illness.

          -  Pregnancy, due to the unknown effects of MRI/MRS scanning on a developing fetus.

          -  Females of childbearing potential who are unable or unwilling to practice
             contraception during the study.

          -  Positive urine pregnancy test.

          -  Contraindication to MRI/MRS scanning, such as ferromagnetic implant or claustrophobic
             anxiety.

          -  Documented or suspected history of mental retardation (Full-Scale I.Q. < 70).