Can Creatine Help with Depression?

“I didn’t want to wake up.
I was having a much better time asleep. And that’s really sad.
It was almost like a reverse nightmare, like when you wake up from a nightmare you’re so relieved. I woke up into a nightmare.” –Ned Vizzini, It’s Kind of a Funny Story



Few conditions can be as devastating as depression. The disorder has links with cancer, diabetes, chronic pain, thyroid disorders, multiple sclerosis, and heart disease. Approximately 7% of men and 1% of women with a lifetime history of depression die from suicide.

“The so-called ‘psychotically depressed’ person who tries to kill herself doesn’t do so out of quote ‘hopelessness’ or any abstract conviction that life’s assets and debits do not square. And surely not because death seems suddenly appealing. The person in whom its invisible agony reaches a certain unendurable level will kill herself the same way a trapped person will eventually jump from the window of a burning high-rise.” – David Foster Wallace


Treatment of Depression

While antidepressant drugs have been a lifesaver for many people, they fail to help a significant number of users. In studies of adults, 40 to 60 of 100 people who used an antidepressant noticed improvement within six to eight weeks, compared to 20 to 40 who received a placebo.1

The drugs can also have significant side effects in many people and, in some cases, make the condition worse.

In an effort to obtain relief from what has been termed a “half-life,” depressed individuals may turn to psychotherapy or group therapy. These nondrug therapies can be helpful, although depression is considered to be a biochemical disorder. Nevertheless, it can’t be denied that our thoughts have profound effects on our bodies.

“There is no point treating a depressed person as though she were just feeling sad, saying, ‘There now, hang on, you’ll get over it.’ Sadness is more or less like a head cold— with patience, it passes. Depression is like cancer.” –Barbara Kingsolver, The Bean Trees

Nutritional Solutions: Creatine Research

Good nutrition is the foundation of a sound body and mind. Essential vitamins, minerals, and amino acids all play a role in our mental well-being. Individualized nutritional regimens can be tweaked with the addition of supplements like creatine that have shown promise in preliminary studies. Creatine can also be made in the body from the amino acids arginine, glycine, and methionine.

Creatine plays a vital role in brain energy metabolism,” Tracy L. Hellem, PhD, RN, and colleagues note in a recent article. “Via the creatine kinase reaction, creatine facilitates production of adenosine triphosphate, the nervous system’s principal energy source.”2

A small, preliminary study of creatine monohydrate in eight patients with unipolar depression and two bipolar patients with treatment-resistant depression found significant improvement among the unipolar patients at the end of the four-week study.3

In 2017, the Journal of Clinical Psychopharmacology reported findings from a pilot study that found a benefit for treatment with creatine and 5-hydroxytryptophan (5-HTP, a metabolite of the amino acid tryptophan) among women with major depressive disorder who hadn’t experienced improvement with with selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) drugs.4 Depression scores declined by an average of 60% from pretreatment values after treatment with 5 grams of creatine monohydrate daily and 100 mg of 5-HTP twice daily for eight weeks.

Research suggests that creatine may be particularly effective in women. In depressed women with methamphetamine dependence, eight weeks of daily supplementation with 5 grams of creatine monohydrate resulted in a decrease in depression and anxiety scores as early as the second week of treatment and a reduction in methamphetamine-positive urine drug screens of greater than 50% by week six.2 Treatment increased brain phosphocreatine concentrations, which are reduced in treatment-resistant depression.

“The exact antidepressant mechanism of creatine is not clear, but one possible explanation involves its role in cellular energy metabolism given that accumulated evidence suggests that altered cellular energy metabolism is involved in the pathophysiology of depression,” the authors write. “Since creatine plays a critical role in cellular energy homeostasis, treatment with it might improve cellular energy metabolism.”

A placebo-controlled study that included adolescent girls with SSRI-resistant major depressive disorder found that eight weeks of daily creatine monohydrate supplementation increased mean frontal lobe phosphocreatine levels from pretreatment values, while levels in the placebo group declined.5 Higher phosphocreatine levels were correlated with lower depression scores. The authors note that converging lines of evidence indicate that mitochondrial dysfunction and altered brain bioenergetics could contribute to the etiology of depression. They further indicate that, in mitochondria, phosphocreatine is reversibly converted during the creatine kinase reaction into ATP (adenosine triphosphate) and creatine and that neuronal energy demands are met through a shift in reaction equilibrium, which is designed to keep brain ATP concentrations constant.

In a randomized, double-blind trial that included 52 women with major depressive disorder, participants who received creatine for eight weeks experienced greater improvement in depressive symptoms than those in the placebo group. Women who received creatine also experienced improvement in brain energy metabolism and network organization, which the authors of the report suggest may partly underlie its efficacy.6

Closing Thoughts

While creatine could offer a glimmer of hope to many adults with treatment-resistant depression, those who are being helped by antidepressants should not attempt to replace their drug regimen with creatine.

Supplementation with creatine is not suggested for depressed children or pregnant and lactating women. Individuals who are experiencing depression are advised to first consult their physician to determine the form of therapy that is right for them.

References

  1. Institute for Quality and Efficiency in Health Care. 2017 Jan 12. Depresson: How effective are antidepressants? PubMed Health. Retrieved from https://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0087089/ Accessed 29 Jul 2018.
  2. Hellem TL et al. J Dual Diagn. 2015;11(3-4):189-202.
  3. Roitman S et al. Bipolar Disord. 2007 Nov;9(7):754-8.
  4. Kious BM et al. J Clin Psychopharmacol. 2017 Oct;37(5):578-583.
  5. Kondo DG et al. Amino Acids. 2016 Aug;48(8):1941-54.
  6. Yoon S et al. Biol Psychiatry. 2016 Sep 15;80(6):439-447.

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