A compelling new study is building on a growing body of evidence showing a common exercise supplement used to build muscle may also confer beneficial mental health outcomes. The small trial demonstrated how adding creatine to a course of cognitive behavioural therapy can lead to greater reductions in depressive symptoms after eight weeks compared to patients receiving psychotherapy alone.
The world of exercise supplements is filled with misinformation and pseudoscience. In fact, the commonly used term ‘nutraceutical’ originated as a marketing term designed to make certain dietary supplements sound more sciency. The advertising equivalent of jazz hands – giving a product the veneer of proof without any actual substance.
Having said all of that, creatine is probably one of the few supplements out there that actually has the backing of decades of scientific research. A quick search of any article database will unearth hundreds of studies trying to parse the pros and cons of creatine supplementation. And as with most heavily researched subjects, you can find studies arguing for and against creatine’s various uses. However, at this point in 2025, one can pretty comfortably say that creatine can be a very helpful supplement for those looking to build muscle mass and speed up recovery from high-intensity exercise. It is also relatively safe when used in recommended dosages.
More recently, researchers have begun to look at the broader systemic effects of creatine supplementation. Of particular interest has been the relationship between creatine and brain health. Following the discovery of endogenous creatine synthesis in the human brain, research quickly moved to understand what role this compound plays in things like cognition and mood.
Most studies linking brain benefits to creatine supplementation are either small or preliminary but there are enough clues to suggest that something positive could be going on here. For example, one oft-cited clinical trial from 2012 found creatine supplementation can effectively augment anti-depressant treatment. The trial was small (just 52 subjects, all women) but after eight weeks it found those subjects taking creatine supplements with their SSRI antidepressant were twice as likely to achieve remission from depression symptoms compared to those just taking antidepressants.
A recent article reviewing the research on creatine supplementation and depression pointed to several physiological mechanisms that could plausibly explain how this compound could improve mental health. Alongside citing several small trials that found positive results from creatine supplementation, the article concludes by stating:
"Creatine is a naturally occurring organic acid that serves as an energy buffer and energy shuttle in tissues, such as brain and skeletal muscle, that exhibit dynamic energy requirements. Evidence, deriving from a variety of scientific domains, that brain bioenergetics are altered in depression and related disorders is growing. Clinical studies in neurological conditions such as PD [Parkinson's Disease] have indicated that creatine might have an antidepressant effect, and early clinical studies in depressive disorders – especially MDD [Major Depressive Disorder] – indicate that creatine may have an important antidepressant effect."
A new study, the result of an international collaboration between researchers in the UK and India, has taken a novel approach with the subject. This team wondered whether creatine supplementation could enhance the efficacy of psychotherapy, in the absence of any other pharmaceutical intervention.
So around 100 subjects were recruited, all diagnosed with acute major depression. For the duration of the trial every participant received biweekly cognitive behavioral therapy – five 45-minute sessions in total. Half of the cohort was given five grams of oral creatine monohydrate daily, while the other half was given equal amounts of a starch placebo.
At the end of the eight-week study the creatine group reported notably lower depression severity scores than the placebo group. Using a depression measure known as the Patient Health Questionnaire (PHQ)−9, subjects in the creatine group showed a mean improvement of five points over the placebo group. This effectively meant the creatine doubled the efficacy of the psychotherapy, with 12 participants in the supplement group achieving full remission at the end of the eight weeks compared to just five in the placebo group.
It is important to add some caveats here, as the researchers are clear in noting their results are preliminary. These findings cannot be used to influence clinical advice so far, however, there is certainly something going on here that is worthy of further research. Creatine is inexpensive and known to be relatively safe, so the study does conclude it to be a “feasible intervention in under-resourced settings” when psychotherapy sessions are limited.
The new research was published in the journal European Psychopharmacology.