Creatine supplements show potential for managing major depressive disorder

A recent systematic review suggests that creatine monohydrate, a popular supplement often used by athletes to build muscle, might offer benefits for treating certain mental health conditions, particularly major depressive disorder. Published in The Canadian Journal of Psychiatry, the review provides evidence that adding creatine to standard treatments like antidepressants or talk therapy tends to improve depressive symptoms in adults. These findings open the door to using easily accessible dietary supplements to support traditional psychiatric care.

Psychiatric disorders like depression and bipolar disorder are widespread conditions that can severely impact a person’s quality of life. Standard medications help many patients manage their symptoms. Some individuals experience unwanted side effects or only partial relief from these traditional treatments. This reality has prompted researchers to explore alternative options, including dietary supplements, to support brain health.

One promising supplement is creatine monohydrate. Creatine is a naturally occurring compound found in the body and obtained through foods like meat and fish. It plays a central part in managing cellular energy.

Tissues that require a lot of energy, such as the brain, rely heavily on creatine. The primary molecule that stores and transfers energy within our cells is called ATP. When brain cells consume energy, they break down ATP, which then becomes a depleted molecule called ADP. During demanding mental processes, creatine acts like a quick backup battery, donating a specific chemical component to turn the depleted ADP back into functional ATP.

Emerging research suggests that mental health conditions, particularly major depressive disorder and bipolar disorder, might involve problems with brain energy metabolism and the function of mitochondria. Mitochondria are the microscopic energy-producing structures inside our cells. A deficiency in brain energy can alter how nerve cells communicate, which could contribute to mood disturbances.

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Because some previous studies reported mixed findings regarding creatine’s ability to improve mood and cognition, the authors of this new review decided to gather and evaluate the highest quality evidence available. This research team was led by co-first authors Bassam Jeryous Fares, Carl Zhou, Nicholas Fabiano, and Stanley Wong, who are affiliated with the University of Ottawa and the University of Toronto in Canada. They aimed to determine if supplementing with creatine monohydrate improves psychiatric symptoms. They also wanted to assess whether the supplement is safe for patients with established mental disorders.

The researchers conducted a systematic review, meaning they systematically searched multiple scientific databases to find all the relevant studies on this topic. They specifically looked for randomized controlled trials. These trials are considered a high standard in science because they randomly assign participants to receive either the active treatment or an inactive placebo.

The final review included five of these trials, encompassing a total of 238 participants. The average age of the participants was 36, and about a quarter of them were male. Four of the trials focused on major depressive disorder, and one trial examined bipolar depression.

Two published articles in the review analyzed data from the exact same trial, which involved 52 adult women with major depressive disorder. The participants took an antidepressant medication called escitalopram, a common type of drug known as an SSRI. Half of the women were also given creatine monohydrate, starting at three grams per day and increasing to five grams per day, and the other half received a placebo. The trial lasted eight weeks.

The scientists found that the women taking creatine experienced a larger reduction in their depressive symptoms compared to the placebo group. Symptom changes were measured using established clinical questionnaires, such as the Hamilton Depression Rating Scale, which assesses issues like mood, insomnia, and agitation. By the end of the study, 52 percent of the patients on creatine reached remission, compared to only about 26 percent of those on the placebo.

In a subset of these women, brain imaging showed positive physical changes. Creatine supplementation increased a specific brain chemical marker associated with cellular health and mitochondrial function. This increase in the chemical marker correlated with better mood, which provides evidence that the supplement directly aided brain cell activity.

Another trial looked at 18 adults with major depressive disorder who had not responded well to their previous antidepressant medications. The participants continued their standard medications and were given either five grams of creatine, ten grams of creatine, or a placebo every day for four weeks. In this specific trial, all groups showed some symptom improvement. The researchers found no significant differences between those taking the supplement and those taking the placebo.

A third trial focused on a younger demographic, specifically 33 female adolescents with major depressive disorder. These adolescents had been taking an SSRI medication for at least eight weeks prior to the study. They were randomly assigned to receive daily creatine doses of two, four, or ten grams, or a placebo, for a duration of eight weeks.

Similar to the previous trial, the researchers observed no significant difference in depression scores between the different dosing groups and the placebo group at the end of the eight weeks. They did note that the adolescents taking ten grams of creatine a day showed an increase in stored brain energy. This increase in brain energy correlated with lower depression scores.

The fourth trial explored creatine combined with talk therapy rather than medication. This trial included 100 adults with major depressive disorder who were not taking any psychiatric medications. All participants attended cognitive behavioral therapy, a common form of psychological treatment, every two weeks. Half of the group also took five grams of creatine daily, and the rest took a placebo. After eight weeks, the patients receiving both talk therapy and creatine reported lower depression scores than those receiving talk therapy and a placebo.

The final trial examined bipolar disorder. It included 27 adults who were currently experiencing a depressive episode. The participants were already taking established medications, such as mood stabilizers or antipsychotics. They were given either six grams of creatine or a placebo daily for six weeks.

The trial revealed no significant differences in symptom improvement between the two groups. In the group taking the supplement, two patients developed symptoms of mania, a state of elevated and hyperactive mood. This indicates a need for caution when using energy-enhancing supplements in bipolar populations.

Across the five trials, the supplement was generally well-tolerated by participants. Some individuals reported mild side effects, such as stomach discomfort, nausea, or headaches. These side effects occurred at similar rates in both the treatment and placebo groups, suggesting they were not exclusively caused by the creatine.

Interpreting these findings requires recognizing a few limitations. Because the sample sizes in these trials were relatively small, the findings might not apply to everyone with a mental health condition. The trials also lasted only four to eight weeks. Mental health conditions usually require long-term management, so it is unknown if the benefits of the supplement would last over months or years.

The dosages used in most of these trials were five grams per day or less. Some scientists suspect that this amount might be too low to significantly raise creatine levels in the brain. The review also focused almost entirely on major depressive disorder, meaning these results cannot simply be generalized to other conditions like schizophrenia or anxiety.

Future research should involve larger groups of people over longer periods. Scientists might explore using higher daily doses of the supplement to see if it produces a stronger effect on brain energy. Future studies could also test the supplement alongside other interventions, such as physical exercise, to see how lifestyle changes and dietary supplements might work together to support mental health.

The paper, “The Effect of Creatine Monohydrate on Mental Disorders: A Systematic Review of Randomized Controlled Trials,” was authored by Bassam Jeryous Fares, Carl Zhou, Nicholas Fabiano, Stanley Wong, Brendon Stubbs, Risa Shorr, David Puder, Darren G. Candow, Sergej M. Ostojic, and Marco Solmi.