Adding 5‑HTP and creatine to antidepressants for people with SSRI/SNRI‑resistant depression

31P-MRS and resting state functional connectivity analysis of the effects of 5-hydroxytryptophan and creatine for antidepressant augmentation in patients with SSRI/SNRI-resistant major depressive diso

NIH-funded research Utah State Higher Education System--University of Utah · NIH-11111318

This project seeks to see if taking 5‑HTP, creatine, or both alongside current SSRIs or SNRIs can change brain energy, brain connectivity, and blood serotonin in people whose depression hasn't improved.

Quick facts

Grant typeNIH-funded research
Study typeNIH-funded research
Funding institutionUtah State Higher Education System--University of Utah NIH-funded
Lab location1 site (Salt Lake City, United States)
Project IDNIH-11111318 on NIH RePORTER

What this research studies

You would join a three‑arm clinical trial comparing 5‑HTP, creatine monohydrate, or the two combined as add‑on supplements for people already taking SSRIs or SNRIs but still depressed. The team will use phosphorus magnetic resonance spectroscopy to measure frontal cortical bioenergetics, resting‑state fMRI to measure subgenual cingulate connectivity, and whole‑blood tests to measure serotonin. The work is motivated by links between low oxygen (for example at high altitude or in asthma) and depression, and by the idea that creatine may help brain energy while 5‑HTP may boost serotonin. The initial R61 phase develops the trial and the R33 phase will run the full study if milestones are met.

Who could benefit from this research

Good fit: Adults with major depressive disorder who remain symptomatic despite an adequate trial of an SSRI or SNRI and who can undergo MRI scans and blood draws would be ideal candidates.

Not a fit: People not taking SSRIs/SNRIs, those with primary bipolar disorder or active psychosis, or those unable to have MRI scans or take the supplements (for example pregnancy or certain medical contraindications) may not benefit or be eligible.

Why it matters

Potential benefit: If successful, this could offer affordable supplement options to help some people who do not respond to standard SSRIs or SNRIs and provide biological measures to guide treatment.

How similar studies have performed: Small clinical and preclinical studies suggest mood or biochemical effects from creatine or 5‑HTP individually, but this combined, biomarker‑driven augmentation approach is relatively novel and not yet proven in large trials.

Where this research is happening

Salt Lake City, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.