Study of 5-Hydroxytryptophan and Creatine Supplements to Improve Antidepressant Treatment in Adults with Major Depressive Disorder Resistant to SSRISNRI

What this Trial Is About

This research aims to evaluate the effects of 5-hydroxytryptophan 5-HTP and creatine monohydrate as augmenting agents for the treatment of major depressive disorder MDD that is resistant to standard antidepressants. The study focuses on addressing the potential impact of relative hypoxia on depression through alterations in brain bioenergetics and serotonin synthesis, investigating biological markers linked to depression and antidepressant response. This phase 2 trial involves participants diagnosed with MDD who have not fully responded to selective serotonin reuptake inhibitors SSRIs or serotonin-norepinephrine reuptake inhibitors SNRIs. Participants will be randomly assigned to one of three groups for 8 weeks a low dose group receiving 5-HTP 100 mg twice daily plus creatine 5 g daily, a high dose group receiving 5-HTP 200 mg twice daily plus creatine 10 g daily, or a placebo group receiving matched placebos for both agents. The study will assess the biological and clinical effects of these treatments by measuring brain phosphorus magnetic resonance spectroscopy 31P-MRS, resting state functional connectivity imaging fcMRI, and plasma serotonin levels, aiming to replicate and extend findings from an earlier phase. During the study, participants will undergo clinical assessments including the 17-item Hamilton Depression Rating Scale to monitor changes in depression severity, as well as secondary measures like the Montgomery-Asberg Depression Rating Scale. Brain imaging and blood tests will be conducted to evaluate changes in brain energy metabolism and serotonin. Safety monitoring includes screening for medical conditions and pregnancy, with study visits scheduled over the 8-week treatment period. The total duration of participation aligns with the treatment timeline, and the study uses quadruple masking to ensure unbiased results.

5-HTP and Creatine for Depression R33 Phase