Creatine as an Adjunctive Treatment for Adolescent Females with Treatment-Resistant Major Depressive Disorder

Principal Investigator: Perry Renshaw
Keywords: Major Depressive Disorder , Child and Adolescent Psychiatry , Creatine , MRI , SSRI Department: Adult Psychiatry
IRB Number: 00073442 Co Investigator: Douglas Kondo
Specialty: Psychiatry, Child and Adolescent, Psychiatry
Sub Specialties: Mood Disorders
Recruitment Status: Recruiting

Contact Information

Samantha Sherwood
sammie.sherwood@utah.edu
(385)228-3576

Brief Summary

Purpose: This pilot study will evaluate the feasibility of recruitment, retention, randomization, participant assessments, and implementation of creatine supplementation as a treatment for adolescent females with treatment-resistant major depressive disorder.  Additionally, this study will estimate the effect size of adjunctive creatine, to inform the design and implementation of a potential future efficacy trial.

Objectives: The primary hypothesis is that compared to placebo, 10g of daily creatine monohydrate for eight weeks will be associated with significant increases in frontal lobe PCr and b-NTP concentrations.  A secondary hypothesis is that decreased depressive symptoms measured with the CDRS-R and Montgomery Asberg Depression Rating Scale (MADRS) will be reciprocally correlated with increased b-NTP concentrations.
 

Inclusion Criteria

MAJOR DEPRESSIVE DISORDER SUBJECTS (n=66)

1. Participants must be female.

2. Participants must be able to grant informed consent (age >18), or parent/guardian permission plus participant assent (age <18).

3. Participants must meet DSM-IV criteria for MDD, with current mood state depressed for >2 weeks.

4. Participants must be between the ages of 12 and 21.

5. Current CDRS-R raw score of >40 or MADRS score >25; and CGI-S score >4.

6. Participants may be enrolled in individual and/or group psychotherapy, if it has been ongoing for at least 8 weeks.

7. Participants must have been in treatment with an SSRI for at least 8 weeks, the last 4 of which were at a dosage of >20 mg per day of fluoxetine or its equivalent, e.g. 20 mg per day of paroxetine, 20 mg citalopram, 10 mg escitalopram, or 100 mg sertraline.  If the participant attempted, but could not tolerate, a dose comparable to 20 mg fluoxetine, they will be considered eligible.  (This definition of "Adolescent SSRI Resistant Depression" is modified from the NIH-sponsored, $17 million TORDIA Randomized Controlled Trial [http://clinicaltrials.gov/ct2/show/NCT00018902] [128]. 

HEALTHY COMPARISON SUBJECTS (n=40)

1. Participants must be able to grant informed consent (age >18), or parent/guardian permission plus participant assent (age <18).

2. Participants must be female.

3. Participants must be between the ages of 12 and 21 years.

4. Participants must not meet DSM-IV-TR criteria for a current psychiatric illness or substance use disorder.

5. Participants must have a CDRS-R score <30.

Exclusion Criteria

MAJOR DEPRESSIVE DISORDER SUBJECTS (n=66)

1. Unstable co-morbid medical, neurological, or psychiatric disorder. 

2. Current DSM-IV criteria for substance abuse or dependence (excepting nicotine/cigarettes).

3. Clinically significant suicidal or homicidal risk.

4. Pre-existing renal disease.

5. Proteinuria on baseline urinalysis testing.

6.. Pregnancy or breastfeeding.

7. Sexually active and unwilling to practice contraception during the study.

8. Contraindication to magnetic resonance imaging (e.g. ferromagnetic implant or claustrophobia)

9. History of hypersensitivity to creatine.

10. History of a previous failed therapeutic trial of creatine.

11. Participants may be outpatients or inpatients, but incarcerated persons will be excluded because this study is not approved for "Research Involving Prisoners."

12. More than 2 suicide attempts prior to the screening visit

13. Participants who made a suicide attempt within 6 months prior to the screening visit

HEALTHY COMPARISON SUBJECTS (n=40)

1. Unstable medical or neurological illness.

2. Clinically significant psychiatric or substance use disorder.

3. Pregnant subjects, due to the unknown effects of MRI/MRS scans on a fetus.  In addition, women of childbearing potential who are unable or unwilling to practice contraception during the study will be excluded.  Female participants who are of childbearing potential must have a negative urine pregnancy test before the MRI/MRS scan.

4. Participants with a contraindication to MRI/MRS scanning, such as a metallic implant.