The Effect of Creatine Monohydrate on Mental Disorders: A Systematic Review of Randomized Controlled Trials: Effet du monohydrate de créatine sur les troubles mentaux : examen systématique des essais contrôlés à répartition aléatoire.
Level 1 - systematic review of randomized trials
Systematic review of randomized controlled trials
PubMed 41558805 · doi:10.1177/07067437251408171
What was done
This systematic review searched MEDLINE, Embase, Cochrane, and PsycINFO through September 30, 2025, for randomized controlled trials (RCTs) evaluating the efficacy and safety of adjunctive creatine monohydrate (CrM) supplementation for psychiatric symptoms in participants with mental disorders. Risk of bias was assessed across included studies.
What was found
Six articles from five RCTs met inclusion criteria (total n = 238; CrM n = 126, placebo n = 112; mean age 36 ± 14 years; 26% male). Four RCTs evaluated major depressive disorder (MDD) and one evaluated bipolar depression; no other mental disorders were studied. Two RCTs had a low risk of bias and three had some concerns. Doses ranged from 2 to 10 g/day for 4 to 8 weeks as adjunct treatment. In adult MDD, CrM combined with escitalopram outperformed escitalopram plus placebo (1 trial, Cohen's d = 1.13 at 8 weeks), and CrM combined with cognitive behavioral therapy (CBT) outperformed CBT plus placebo (1 trial). CrM augmentation showed no difference versus placebo in female adolescents with MDD (1 trial) or in bipolar depression (1 trial). In two MDD trials, CrM-related brain N-acetylaspartate and phosphocreatine increases correlated with symptom improvement. CrM was generally well-tolerated, though 2 of 17 CrM participants experienced hypomania or mania.
Why it matters
Adjunctive creatine monohydrate shows preliminary promise for augmenting standard antidepressants or psychotherapy in adults with major depressive disorder, potentially offering an accessible metabolic add-on strategy.
Limits
The total evidence base is small (five RCTs, 238 total participants), with each specific clinical scenario evaluated in only a single small trial. Three of five trials had risk of bias concerns, data outside adult MDD were null or absent, and treatment-emergent hypomania or mania occurred in 2 of 17 participants.
Cited by
- supports All published clinical studies evaluating creatine for depression have administered it as an adjunct to antidepressant therapy rather than as a monotherapy.