How can augmenting conventional antidepressants with creatine monohydrate help patients with depression?
Depression, a prevalent neuropsychiatric disorder, poses a significant burden on global health.1 Traditional antidepressants, primarily targeting monoaminergic neurotransmitter systems, often require weeks to manifest their therapeutic effects. Moreover, a significant proportion of patients do not respond adequately to these treatments.2
Thus, there is an increasing interest in exploring novel therapeutic strategies. One such promising approach is the augmentation of conventional antidepressants with creatine monohydrate, a supplement known for its ergogenic benefits and potential neuroprotective properties.3
Creatine and Brain Energy Metabolism
Creatine plays a crucial role in brain energy homeostasis.4 Disruptions in brain energy production, storage, and utilization have been implicated in the pathophysiology of depression.5 Creatine supplementation may modify brain high-energy phosphate metabolism, potentially restoring bioenergetics at the cellular level.2
The brain, being an energy-intensive organ, relies heavily on adenosine triphosphate (ATP) for its functions. Creatine, stored as phosphocreatine in cells, acts as a reservoir for high-energy phosphate, which can be rapidly mobilized during periods of high energy demand. This mechanism is particularly crucial in neurons, which have limited energy reserves.
Several studies have investigated the potential antidepressant properties of creatine (Table).3,6-9
However, although some studies have reported beneficial effects of creatine for depression management, others have found no significant advantage compared to placebo.10
The exact mechanisms through which creatine exerts its antidepressant effects are still under investigation. However, several theories have been proposed:
Safety and Tolerability
Creatine is generally well-tolerated, with most reported adverse effects being mild and transitory.6 Common adverse effects include gastrointestinal symptoms and muscle cramping. However, in the context of depression treatment, these adverse effects are often outweighed by the potential benefits.
Although the current body of research suggests that creatine supplementation may offer a novel therapeutic approach for depression, especially in treatment-resistant cases, further randomized, placebo-controlled trials are warranted. The potential of creatine to restore brain bioenergetics, combined with its safety profile, makes it an attractive candidate for future research in the realm of neuropsychiatric disorders.3
Dr Ajluni is an assistant professor of psychiatry at Wayne State University in Livonia, Michigan.
During the preparation of this work, the author used ChatGBT in order to synthesize and summarize information based on my ideas, input, and conclusions. After using this tool/service, the author reviewed and edited the content as needed and takes full responsibility for the content of the publication.
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