Can Creatine Help Treat Depression? A New Review Weighs the Evidence
Creatine showed mixed results as an adjunct treatment for depression across clinical trials.
While creatine is a staple in gym bags for building muscle, it may also play a role in managing mental health.
Researchers at the University of Ottawa recently conducted a systematic review of international trials to see if creatine could help treat depression. The final data revealed a deeply divided picture, with the supplement showing significant benefits in some patients but failing completely in others.
Why scientists are studying creatine for depression
The brain is an energy-expensive organ, using ~20% of the body’s resting energy, despite only making up ~2% of total body weight. Previous research has identified that when energy production in the brain drops, mood disorders can follow.
“There is a growing body of evidence that brain energetics contribute to depression, but it more likely forms a piece of the multifactorial puzzle alongside various other mechanisms via a biopsychosocial lens,” corresponding author Dr. Nicholas Fabiano, a psychiatry resident at the University of Ottawa, told Technology Networks.
Many people with major depressive disorder find that standard antidepressants provide only a partial or suboptimal response, driving the search for effective add-on therapies.
Creatine can help cells quickly replenish adenosine triphosphate, the primary molecule used for cellular energy, making the supplement potentially relevant to brain energetics issues. Researchers have also linked altered brain creatine metabolism to conditions such as depression. However, although limited in number, previous clinical trials evaluating creatine for depression have yielded scattered, inconsistent, and purely correlational results.
“I was surprised by how little literature exists on [creatine and] mental disorders apart from depression,” said Fabiano.
The new study aimed to systematically evaluate the efficacy, safety, and dosing of creatine as an adjunctive treatment across existing randomized controlled trials (RCTs) across all mental disorders.
What clinical trials reveal about creatine and mood disorders
The new systematic review synthesized data from five international RCTs spanning five countries: South Korea, the United States, Brazil, Israel, and India. They analyzed six records encompassing 238 baseline participants. Instead of pooling the numbers in a single statistical meta-analysis, the authors chose to use a narrative summary as the individual studies differed too widely in their designs.
The results revealed a deeply divided clinical picture.
On one hand, two studies drawn from a single trial found that adding 5 g/day of creatine to the standard antidepressant escitalopram significantly decreased depressive symptoms in women with major depressive disorder after eight weeks. These patients also achieved notably higher remission rates. Another trial showed enhanced benefits when researchers paired creatine with cognitive behavioral therapy rather than a placebo.
However, the remaining three trials found no therapeutic benefit at all. Creatine failed to outperform a placebo across various doses, ranging from 2 g to 10 g/day, in treatment-resistant patients, adolescent girls, and people experiencing a bipolar depressive episode.
While the supplement was generally well-tolerated with only mild digestive issues, it triggered hypomania or mania in two patients with bipolar disorder; “this is an early signal, which certainly warrants further investigation,” warned Fabiano.
The team found no clinical trials evaluating creatine for any mental health conditions outside of mood disorders.
The limitations and future of creatine for depression
The split results highlight limitations in the current literature. The included trials suffered from small sample sizes and carried varying risks of bias regarding how researchers randomized patients and handled missing data.
It is also difficult to pool the data together, due to “how different all the included trials were in terms of patient population, dose of creatine, other treatments the patients were receiving simultaneously, among others,” explained Fabiano.
There is also a severe generalizability gap, as most participants were women, and two trials enrolled women exclusively. Though, notably, rodent studies show that creatine alters depression-like behavior in a sex-dependent manner, which might explain why the female-heavy human trials showed more clinical promise.
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With this large discrepancy in findings, the current evidence cannot alter standard psychiatric practice.
“The research is still nascent,” said Fabiano. “We cannot yet reliably say that creatine helps with depressive symptoms or if the findings are generalizable to everyone.”
The authors call for larger, longer-term trials exceeding eight weeks.
“We need a large-scale clinical trial demonstrating its efficacy across a variety of patient populations at various doses,” added Fabiano. “It would be great to have a trial looking at just using creatine (and no other treatment) in mild to moderate depression.”
“The signal is interesting, but it is not a verdict. Two trials pointed one way and three pointed another. That is not the kind of evidence on which you change clinical practice. It is the kind that tells you the question is worth further exploration,” concluded first author Bassam Jeryous Fares, a student in the Faculty of Medicine at the University of Ottawa.
Reference: Jeryous Fares B, Zhou C, Fabiano N, Wong S. Creatine as a treatment for depression. Brain Med. 2026:1-2. doi: 10.61373/bm026l.0039
About the interviewee:
Dr. Nicholas Fabiano is a 5th year psychiatry resident and researcher at the University of Ottawa. He has an interest in lifestyle psychiatry with a particular focus on exercise, diet, and sleep for mental health. He has published over 90 peer-reviewed papers and was recently awarded the The Association of Chairs of Psychiatry of Canada (ACPC) Annual Research Award.
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