title: Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study.
abstract: BACKGROUND
  Adolescent major depressive disorder (MDD) is a life-threatening brain disease with limited interventions. Treatment resistance is common, and the illness burden is disproportionately borne by females. 31-Phosphorus magnetic resonance spectroscopy ((31)P MRS) is a translational method for in vivo measurement of brain energy metabolites.
  
  
  METHODS
  We recruited 5 female adolescents who had been on fluoxetine (Prozac®) for ≥ 8 weeks, but continued meet diagnostic criteria for MDD with a Children's Depression Rating Scale-Revised (CDRS-R) raw score ≥ 40. Treatment response was measured with the CDRS-R. (31)P MRS brain scans were performed at baseline, and repeated following adjunctive creatine 4 g daily for 8 weeks. For comparison, 10 healthy female adolescents underwent identical brain scans performed 8 weeks apart.
  
  
  RESULTS
  The mean CDRS-R score declined from 69 to 30.6, a decrease of 56%. Participants experienced no Serious Adverse Events, suicide attempts, hospitalizations or intentional self-harm. There were no unresolved treatment-emergent adverse effects or laboratory abnormalities. MDD participants' baseline CDRS-R score was correlated with baseline pH (p=0.04), and was negatively correlated with beta-nucleoside triphosphate (β-NTP) concentration (p=0.03). Compared to healthy controls, creatine-treated adolescents demonstrated a significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up (31)P MRS brain scans.
  
  
  CONCLUSIONS
  Lack of placebo control; and small sample size.
  
  
  CONCLUSIONS
  Further study of creatine as an adjunctive treatment for adolescents with SSRI-resistant MDD is warranted.
authors.affiliation: The Brain Institute, University of Utah, 383 Colorow Drive, Salt Lake City, UT 84108, USA. doug.kondo@hsc.utah.edu
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Kondo
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Sung
authors.forename: Tracy L
authors.initials: TL
authors.lastname: Hellem
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Fiedler
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Shi
authors.forename: Eun-Kee
authors.initials: EK
authors.lastname: Jeong
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
mesh_terms: D000293:Adolescent; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003401:Creatine / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000139:chemically induced / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008280:Magnetics; D010725:Phosphocreatine / Q000378:metabolism / Q000627:therapeutic use; D010758:Phosphorus / Q000627:therapeutic use; D011877:Radionuclide Imaging; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D003401:Creatine; D005473:Fluoxetine; D010725:Phosphocreatine; D010758:Phosphorus; D017367:Selective Serotonin Reuptake Inhibitors