Around 280 million people have depression worldwide, according to the World Health Organization. The condition is often treated using psychotherapies, pharmacotherapies, or a combination of both – but while these can be incredibly effective for some people, not everyone sees the same benefit.

“Between one-third and one-quarter of patients do not respond to any antidepressant strategy or drop out from any treatment due to inefficacy or adverse events,” the researchers write in their paper. As a result, it’s vitally important that we explore other potential treatment options, to help as many patients as possible find the solution that works for them.

Creatine, when used alongside existing therapies, could be a valuable weapon in our arsenal. The organic compound is present naturally in certain animal-based foods as well as supplements and is produced in our liver and brain, helping to provide cells with energy – hence its use in bodybuilding and other sports. Previous research has hinted at its potential benefits when it comes to depression: it’s shown promise in animal models of depression, and preliminary evidence from several human trials has suggested it may enhance the effects of antidepressant drugs.

Building upon this burgeoning bank of research, the team behind the latest study explored creatine in addition to cognitive behavioral therapy (CBT) – a talking therapy that aims to help patients manage their problems by changing the way they think and behave.

“Creatine could enhance the effects of CBT by promoting cognitive and behavioural functioning while also expressing a direct antidepressant action,” they hypothesize, adding that “to present this has not been tested in a clinical trial setting”.

To investigate, the researchers recruited 100 people in India with mild to severe depression who hadn’t taken antidepressants in at least eight weeks. At baseline, they completed a questionnaire that provided them each with a depression score, ranging from zero (no depression) to 27 (severe depression). At this stage, the average score was 17.6 (moderately-severe depression).

The participants then went on to receive one of two treatments: either 5 grams (0.2 ounces) a day of oral creatine monohydrate; or the same dosage of oral starch, which acted as a placebo. Both treatment plans were accompanied by biweekly CBT. 

After eight weeks, with just 30 people left in each study arm, depression scores were lower in both groups – but significantly more so for those taking creatine. The creatine group now had an average depression score of 5.8 (mild depression), while the placebo group scored 11.9 (moderate depression).

“That’s actually a very, very large effect of creatine,” Brent Kious at the University of Utah, who was not involved in the study, told New Scientist. “Definitely an effect that a patient would notice in terms of well-being.”

It seems, based on these results, that creatine may be able to increase the antidepressant efficacy of CBT. It was also safe and well-tolerated. However, larger, longer, and more diverse trials are needed to fully assess the efficacy of creatine as part of depression treatment. If these prove fruitful, creatine could just cement itself as an effective and inexpensive addition to future antidepressant strategies.

The study is published in the journal European Neuropsychopharmacology.