Trial reportAmino acids2016
Creatine target engagement with brain bioenergetics: a dose-ranging phosphorus-31 magnetic resonance spectroscopy study of adolescent females with SSRI-resistant depression.
Trial report in Amino acids, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 5 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Mitochondrial-inflammation crosstalk in major depressive disorder: molecular mechanisms and therapeutic implications.Molecular psychiatry · 2026Pooled it
- Is altitude a determinant of the health benefits of nature exposure? A systematic review and meta-analysis.Frontiers in public health · 2022Pooled it
- Creatine in Health and Disease.Nutrients · 2021Pooled it
- Differential and spatial expression meta-analysis of genes identified in genome-wide association studies of depression.Translational psychiatry · 2021Pooled it
- Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis.Nutrients · 2020Pooled it
- Effects of six weeks of guanidinoacetic acid supplementation with and without creatine monohydrate on cognitive function and markers of health in healthy adults.Journal of the International Society of Sports Nutrition · 2026Trial
- Effects of creatine supplementation with and without exercise and diet intervention on body composition, cognitive function, and markers of health in middle-aged and older adults.Journal of the International Society of Sports Nutrition · 2026Trial
- A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.Journal of neural transmission (Vienna, Austria : 1996) · 2018Trial
- An Open-Label Pilot Study of Combined Augmentation With Creatine Monohydrate and 5-Hydroxytryptophan for Selective Serotonin Reuptake Inhibitor- or Serotonin-Norepinephrine Reuptake Inhibitor-Resistant Depression in Adult Women.Journal of clinical psychopharmacology · 2017Trial
- The emerging and evolving evidence supporting creatine as an ergogenic aid: history and applications.Journal of the International Society of Sports Nutrition · 2026Review
- Review
- Transcutaneous auricular vagus nerve stimulation improves depressive-like behaviors in CUMS rats through regulation of gut microbiome, serum metabolites, and immune factors.Frontiers in microbiology · 2026Article
- Adaptations in Mitochondrial Function Induced by Exercise: A Therapeutic Route for Treatment-Resistant Depression.International journal of molecular sciences · 2025Review
- Neuroimaging as a Tool for Advancing Pediatric Psychopharmacology.Paediatric drugs · 2025Review
- The role of brain creatine in behavioral health conditions.Frontiers in psychiatry · 2025Review
- Creatine Supplementation in Depression: A Review of Mechanisms, Efficacy, Clinical Outcomes, and Future Directions.Cureus · 2024Review
- Fueling the Firefighter and Tactical Athlete with Creatine: A Narrative Review of a Key Nutrient for Public Safety.Nutrients · 2024Review
- "Heads Up" for Creatine Supplementation and its Potential Applications for Brain Health and Function.Sports medicine (Auckland, N.Z.) · 2023Review
- Creatine as a Therapeutic Target in Alzheimer's Disease.Current developments in nutrition · 2023Review
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Major depressive disorder (MDD) often begins during adolescence and is projected to become the leading cause of global disease burden by the year 2030. Yet, approximately 40 % of depressed adolescents fail to respond to standard antidepressant treatment with a selective serotonin reuptake inhibitor (SSRI). Converging evidence suggests that depression is related to brain mitochondrial dysfunction. Our previous studies of MDD in adult and adolescent females suggest that augmentation of SSRI pharmacotherapy with creatine monohydrate (CM) may improve MDD outcomes. Neuroimaging with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) can measure the high-energy phosphorus metabolites in vivo that reflect mitochondrial function. These include phosphocreatine (PCr), a substrate for the creatine kinase reaction that produces adenosine triphosphate. As part of the National Institute of Mental Health's experimental medicine initiative, we conducted a placebo-controlled dose-ranging study of adjunctive CM for adolescent females with SSRI-resistant MDD. Participants were randomized to receive placebo or CM 2, 4 or 10 g daily for 8 weeks. Pre- and post-treatment (31)P-MRS scans were used to measure frontal lobe PCr, to assess CM's target engagement with cerebral energy metabolism. Mean frontal lobe PCr increased by 4.6, 4.1 and 9.1 % in the 2, 4 and 10 g groups, respectively; in the placebo group, PCr fell by 0.7 %. There was no group difference in adverse events, weight gain or serum creatinine. Regression analysis of PCr and depression scores across the entire sample showed that frontal lobe PCr was inversely correlated with depression scores (p = 0.02). These results suggest that CM achieves target engagement with brain bioenergetics and that the target is correlated with a clinical signal. Further study of CM as a treatment for adolescent females with SSRI-resistant MDD is warranted.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.