The researchers found that patients receiving creatine augmentation showed significantly greater improvement in HAM-D score, in comparison with the control group. by week two (32.0% versus 3.7% respectively, P<0.001). These improved responses were sustained through weeks four (68.0% versus 29.6%, P<0.001) and eight (64% versus 63%, P<0.001).
The overall frequency of adverse events in the two groups was similar (43.4% in the treatment group, vs. 46.4% in the placebo group). The most common adverse events in both groups were tension headache, nausea and/or vomiting, and sleep disturbances. Most of these events occurred during the early phase of treatment and improved without specific interventions.
The researchers commented that “this proof-of-concept study suggests that depression symptoms … may improve to a greater extent in escitalopram-treated depressed patients receiving creatine than in those receiving placebo as early as two weeks after initiation of treatment.” They added that a significantly higher remission rate was observed in the creatine augmentation group (52.0% versus 25.9% respectively), suggesting that creatine augmentation provided benefits not only in speed of response but also in remission rates.
The researchers noted several limitations of their study, including the small number and homogeneity of study subjects (i.e., all female, common ethnicity, and most experiencing their first major depressive episode). They concluded that “replication of the current findings is required in larger study groups and with a longer period of observation” and added that future studies are also required “in order to assess the possibility of the cerebral phosphocreatine level as a relevant biological marker for predicting creatine-induced antidepressant efficacy.”
1. Stassen HH, Delini-Stula A, Angst J. Time course of improvement under antidepressant treatment: A survival-analytical approach. Eur Neuropsychopharmacol. 1993;3:127–135.
2. Lyoo IK, Yoon S, Kim T-S, et al. 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;169:937–945.
3. Graham AS, Hatton RC. Creatine: A review of efficacy and safety. J Am Pharm Assoc. 1999;39:803–810.
4. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53:161–176.
5. Tarnopolsky MA. Clinical use of creatine in neuromuscular and neurometabolic disorders. Subcell Biochem. 2007;46:183–204.
6. Allen PJ, D’Anci KE, Kanarek RB, Renshaw PF. Chronic creatine supplementation alters depression-like behavior in rodents in a sex-dependent manner. Neuropsychopharmacology. 2010;35:534–546.