Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: A 31-phosphorus magnetic resonance spectroscopy study

BackgroundAdolescent 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 (31P MRS) is a translational method for in vivo measurement of brain energy metabolites.MethodsWe 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. 31P 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.ResultsThe 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 31P MRS brain scans.LimitationsLack of placebo control; and small sample size.ConclusionsFurther study of creatine as an adjunctive treatment for adolescents with SSRI-resistant MDD is warranted.