The Relationship Between Creatine and Depression

Recent studies have shown that creatine supplementation, in addition to traditional psychiatric antidepressants like selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SSRIs and SNRIs) can help alleviate depressive symptoms. Oral creatine supplementation may modify brain high-energy phosphate metabolism in depressed subjects.1 Creatine can be used as adjunctive treatment, or supplemental to psychiatric care. 

Generally, psychiatric care and its supplemental treatments are utilized in combination with traditional mental health treatment methods like cognitive-behavioral and dialectical-behavior therapy. If you or a loved one are struggling with depression and looking for comprehensive and holistic mental health care, don’t hesitate to call a member of our care team today. AMFM Mental Health Treatment has over a decade of experience providing compassionate and thorough depression treatment.

creatine and depression

More about Creatine

Creatine phosphate, or creatine monohydrate is a substance found naturally in the body, and helps muscles produce energy, acting much like amino acids, like glycine and arginine.2 Historically, it’s been used as a dietary supplement for athletes, used in weight lifting to improve strength and performance, but recent studies have shown that oral creatine monohydrate can have a positive effect on a variety of disorders and complications. 

A number of clinical applications of creatine supplementation have been studied involving neurodegenerative diseases, gastrointestinal function, diabetes, fibromyalgia, aging, brain and heart ischemia, adolescent depression, and pregnancy. These studies show that creatine can not only improve exercise performance, but can play a role in preventing and/or reducing the severity of injury, enhancing rehabilitation from injuries, and helping athletes tolerate heavy training loads.3 Creatine stands out as a supplement frequently used for athletics and muscle performance, but it also is a neuroprotective compound with potential to treat or mitigate a broad range of central nervous systems diseases.4

How Does Creatine Monohydrate Work?

Creatine essentially serves as an “energy buffer,” which occurs in both the muscles as well as in the brain: creatine is converted to phosphocreatine (PCr) by the creatine kinase reaction, thereby storing energy in a more stable form than is provided by adenosine triphosphate (ATP).5 The effects of creatine supplementation in brain energy metabolism can be, in the cases of depression, when affecting the neurotransmitters that control dopamine and serotonin, more effective than standalone antidepressants.  Creatine monohydrate can have improved effects on the following, which affects brain function and cellular energy:
  • Improved cell signaling
  • Raised anabolic hormones
  • Increased cell hydration
  • Reduced protein breakdown
  • Lower myostatin levels

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More on Depression

Major Depressive Disorder (MDD) or Clinical Depression is a mood disorder that is known for causing persistent sadness, a loss of interest in pleasurable activities, and a range of other emotional and physical symptoms. Symptoms of depression can affect your daily routine, relationships, and overall quality of life. 

Depression can affect individuals of varying ages and other demographics. While depression is more commonly diagnosed among women, men may experience more stigma regarding mental health difficulties, which prevents them from seeking help. Causes of depression can vary, including generics, experiences you’ve had in life, and a chemical imbalance within your brain. In addition to creatine supplementation and antidepressants, depression therapy can help you in overcoming depression. 

Recent Studies about Creatine Supplementation

Double-Blind, Placebo-Controlled Clinical Trial

In a recent study, two groups of people were evaluated–a placebo group and a creatine group. In comparison to the placebo augmentation group, patients receiving creatine augmentation showed significantly greater improvements in HAM-D score (depression scores), as early as week 2 of treatment. This differential improvement favoring creatine was maintained at weeks 4 and 8, with no differences between treatment groups in the proportion of patients who discontinued treatment prematurely or in the overall frequency of all reported adverse events.6 In another similar study on dietary creatine, depression prevalence was 10.23/100 persons (95% CI: 8.64–11.83) among participants in the lowest quartile of dietary creatine consumption compared to 5.98/100 persons (95% CI: 4.97–6.98) among participants in the highest quartile of dietary creatine consumption (p < 0.0001).7

Animal Models

Animal research further underscores the use of creatine for reducing depression symptoms, revealing that blocking serotonin synthesis reduces creatine’s antidepressant-like effects, indicating that the benefits of creatine for depression are at least partially mediated by its effect of enhancing neurotransmitter production and function.8

Neuroimaging for Brain Bioenergetics

Neuropsychopharmacology can be used to observe creatine meeting the brain’s energy demands in individuals struggling with major depression. In one such study, compared to baseline healthy controls, creatine-treated adolescents demonstrated a significant increase in brain Phosphocreatine (PCr) concentration (p=0.02) on follow-up (31)P MRS brain scans.9

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Adjunctive Treatment for Depression

Depression can affect individuals differently, which often requires individualized treatment. In addition to creatine supplementation to psychiatric treatment, there are a variety of depression treatment options that can be used to address the emotional, cognitive, and behavioral aspects of this condition. Some of the most common psychotherapy modalities used in depression counseling sessions include:

Family or Couples Therapy

Couples and family therapy may be used when a loved one’s depressive symptoms are affecting others. This can increase everyone’s understanding of depression and talk about how to support each other. Couples and family therapy sessions can improve communication patterns, focus on problem-solving, address unresolved conflicts, and increase the sense of understanding among one another.

Group Therapy

Group therapy sessions can be used to help provide structured times to help you understand that you are not alone in your struggles, that your peers are also walking through these challenges, while also providing guidance, suggestions and communications from psychologists with specialized backgrounds. These groups can span a variety of backgrounds, including but not limited to art therapy, somatic therapy, and narrative therapy.

Cognitive-Behavioral Therapy (CBT)

Cognitive-Behavioral Therapy (CBT) is a form of therapy that’s focused on restructuring and reprogramming maladaptive and negative thought processes2. Psychologists are trained to help you change your cognitive and emotional processes in order to outgrow coping mechanisms that may no longer be serving you.

Dialectical Behavior Therapy (DBT)

Dialectical Behavior Therapy (DBT) is most commonly referred to as “talk therapy,” and is designed to help process emotions. Qualified professionals offer psychological therapy to move forward with healthy ways of engaging in interpersonal relationships and alleviating physical and emotional distress. 

Eye Movement Desensitization and Reprocessing Therapy (EMDR)

EMDR Therapy is a renowned method of reprocessing most often used in trauma therapy. By activating the prefrontal cortex through a series of bilateral stimulation, qualified professionals can lead you through traumatic experiences, helping you to alleviate the distress symptomized by trauma.10

Health Insurance Coverage for Depression Treatment

Most health insurance companies provide some form of coverage for depression treatment. This often includes both inpatient and outpatient care, depending on your symptoms. Coverage generally applies to therapy, counseling, and medication management services. Your plan may have limitations, exclusions, or required authorizations.

We encourage you to verify your coverage with AMFM Mental Health Treatment to understand the full scope of your insurance plan’s in-network benefits. This is especially true if you’re looking for specific treatments, like postpartum depression treatments or persistent depressive disorder treatment options.

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I understand that I may be contacted by telephone, email, text message or mail regarding my disability benefit case options and that I may be called using automatic dialing equipment. Message and data rates may apply. My consent does not require purchase. Message frequency varies. Text HELP for help. Reply STOP to unsubscribe.

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Our team will verify if your insurance provider is in-network with an AMFM Healthcare Facility.

Contact From Admission Representative:

Expect a call within an hour from an admissions representative to discuss treatment options.

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I understand that I may be contacted by telephone, email, text message or mail regarding my disability benefit case options and that I may be called using automatic dialing equipment. Message and data rates may apply. My consent does not require purchase. Message frequency varies. Text HELP for help. Reply STOP to unsubscribe.

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A Future of Lasting Wellness Awaits at AMFM

A Mission For Michael Mental Health Treatment was founded to bring mental health resources and recovery to those who need it, meeting you with empathy at every step of the way. From admissions to aftercare, our teams are trained to provide the highest level of care, combining compassion with evidence-based personalized treatment plans. Our goal is to encourage and enable long-term behavioral growth and mental well-being in our mental health treatment facilities, to set our clients up for success for the rest of their lives.

You don’t have to embark on this journey alone. Call us to speak confidentially with a member of our care team today.

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Mawer, R. (2023, November 2). Creatine 101: What is it and what does it do?. Healthline. https://www.healthline.com/nutrition/what-is-creatine#basics

Kreider RB, Kalman DS, Antonio J, Ziegenfuss TN, Wildman R, Collins R, Candow DG, Kleiner SM, Almada AL, Lopez HL. International Society of Sports Nutrition position stand: safety and efficacy of creatine supplementation in exercise, sport, and medicine. J Int Soc Sports Nutr. 2017 Jun 13;14:18. doi: 10.1186/s12970-017-0173-z. PMID: 28615996; PMCID: PMC5469049.

Francis L. Pazini, Mauricio P. Cunha, Ana Lúcia S. Rodrigues, The possible beneficial effects of creatine for the management of depression, Progress in Neuro-Psychopharmacology and Biol. Psychiatry, Volume 89, 2019, Pages 193-206, ISSN 0278-5846, https://doi.org/10.1016/j.pnpbp.2018.08.029.

Kious BM, Kondo DG, Renshaw PF. Creatine for the Treatment of Depression. Biomolecules. 2019 Aug 23;9(9):406. doi: 10.3390/biom9090406. PMID: 31450809; PMCID: PMC6769464.

Lyoo IK, Yoon S, Kim TS, Hwang J, Kim JE, Won W, Bae S, Renshaw PF. A randomized, double-blind placebo-controlled trial of oral creatine monohydrate augmentation for enhanced response to a selective serotonin reuptake inhibitor in women with major depressive disorder. Am J Psychiatry. 2012 Sep;169(9):937-945. doi: 10.1176/appi.ajp.2012.12010009. PMID: 22864465; PMCID: PMC4624319.

Bakian, A. V., Huber, R. S., Scholl, L., Renshaw, P. F., & Kondo, D. (2020, February 3). Dietary creatine intake and depression risk among U.S. adults. Translational Psychiatry. https://www.nature.com/articles/s41398-020-0741-x#:~:text=dietary%20creatine%20consumption.-,Depression%20prevalence%20was%2010.23/100%20persons%20(95%25%20CI:,consumption%20(p%20%3C%200.0001)

Attia, P. (2025, April 5). New dietary guidelines aim to optimize public health, not personal health. Peter Attia. https://peterattiamd.com/creatine-and-depression/#:~:text=Small%2C%20unblinded%20studies%20have%20likewise%20shown%20promising,SSRIs%20and%20SNRIs%20were%20paired%20with%20creatine.&text=Animal%20research%20further%20underscores%20this%20synergy%2C%20revealing,effect%20of%20enhancing%20neurotransmitter%20production%20and%20function

Kondo DG, Sung YH, Hellem TL, Fiedler KK, Shi X, Jeong EK, Renshaw PF. Open-label adjunctive creatine for female adolescents with SSRI-resistant major depressive disorder: a 31-phosphorus magnetic resonance spectroscopy study. J Affect Disord. 2011 Dec;135(1-3):354-61. doi: 10.1016/j.jad.2011.07.010. Epub 2011 Aug 9. PMID: 21831448; PMCID: PMC4641570.

“What is EMDR?” EMDR Institute, https://www.emdr.com/what-is-emdr/. Accessed 20 February 2025.