Lyoo · The American journal of psychiatry 2012 · randomized double-blind placebo-controlled trial · n=52

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.

Cited 130 times in the scientific literature.

Level 2 - randomized trial

Individual randomized double-blind placebo-controlled trial.

PubMed 22864465 · doi:10.1176/appi.ajp.2012.12010009 · record verified 2026-08-26

What was done

Fifty-two women with major depressive disorder participated in an 8-week double-blind placebo-controlled trial. All received escitalopram and were randomized to either creatine monohydrate (5 g/day, n=25) or placebo (n=27). The primary outcome was change in Hamilton Depression Rating Scale (HAM-D) scores.

What was found

Creatine augmentation produced significantly greater reductions in HAM-D scores compared with placebo starting at week 2, maintaining significant superiority at weeks 4 and 8 (numeric HAM-D scores not reported in abstract). Premature discontinuation occurred in 32.0% (n=8) of creatine participants versus 18.5% (n=5) of placebo participants, a non-significant difference. Total reported adverse events were 36 with creatine and 45 with placebo.

Why it matters

Adjunctive creatine may accelerate and improve antidepressant response to SSRIs in women with major depressive disorder, potentially overcoming the typical multi-week lag in treatment onset.

Limits

The sample was small (n=52) and restricted exclusively to women. Numerical HAM-D scores, effect sizes, and p-values were omitted from the abstract. Treatment discontinuation was numerically higher in the creatine group.

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