Table 2.
Clinical trials involving creatine for the treatment of depression.
| Study | Population (n) | Design | Creatine Dose | Duration | Effect | Significant Adverse Effects Related to Creatine |
|---|---|---|---|---|---|---|
| Roitman 2007 [186] | MDD-D (n = 8); BD-D (n = 2) | Open-label, adjunctive | 3–5 g/day | 4 weeks | Average HAM-D scores declined from 23.1 at baseline to 12.6 at week 4 | Both bipolar subjects developed hypomania/mania |
| Kondo 2011 [133] | Adolescent girls with MDD-D (n = 5) | Open-label, adjunctive | 4 g/day | 8 weeks | The mean CDRS-R score fell by 50.6% | None |
| Kondo 2016 [170] | Adolescent and young-adult women with MDD-D (n = 34) | Open-label, adjunctive, dose-ranging | 2 g, 4 g, or 10 g/day | 8 weeks | Creatine increased frontal cortical phosphocreatine levels in a fashion associated with lower depression ratings | None |
| Lyoo 2012 [188] | Women with MDD-D (n = 52) | Randomized, double-blind, placebo-controlled, adjunctive | 3 g/day × 1 week then 5 g/day × 7 weeks | 8 weeks | HAM-D scores in the creatine group fell by 79.7% by week 8, compared to 62.5% in the placebo group | None |
| Nemets 2013 [189] | MDD-D (n = 18) | Randomized, double-blind, placebo-controlled, adjunctive | 5 g/day or 10 g/day | 4 weeks | No significant difference between creatine and placebo in HAM-D scores | None |
| Hellem 2015 [193] | Methamphetamine dependence with depression (n = 14) | Open-label, monotherapy | 5 g/day | 8 weeks | Mean HAM-D scores fell to 10.4 by week 2, representing response | Gastrointestinal symptoms (n = 5) and muscle cramps (n = 2) |
| Kious 2017 [190] | Women with MDD-D (n = 15) | Open-label, adjunctive | 5 g/day (with 5-HTP 200 mg twice daily) | 8 weeks | HAM-D scores improved by ~60% by week 8 | None |
| Toniolo 2017 [191] | BD-D (n = 18) | Randomized, double-blind, placebo-controlled, adjunctive | 6 g/day | 6 weeks | Significant improvement in verbal fluency but no significant changes in other measures reported | None |
| Toniolo 2018 [192] | BD-D (n = 53) | Randomized, double-blind, placebo-controlled, adjunctive | 6 g/day | 6 weeks | No significant difference in MADRS scores between groups, but MADRS remission rate was significantly greater in creatine group (52.9% vs. 11.1%) | Two participants in creatine group developed hypomania/mania |
BD-D: bipolar disorder, depressed state; CDRS-R: Children’s Depression Rating Scale, Revised; HAM-D; 17-item Hamilton Depression Rating Scale; MADRS: Montgomery-Asberg Depression Rating Scale MDD-D: major depressive disorder, depressed state.