Creatine Augmentation of SSRIs for Depression

Summary and Comment |
August 20, 2012

Creatine Augmentation of SSRIs for Depression

  1. Joel Yager, MD

In depressed women, adding creatine to an SSRI seems to enhance the medication's antidepressant effects.

  1. Joel Yager, MD

The dietary supplement creatine has been widely promoted for use in building muscles and boosting energy, and Americans use more than 4 million kg of creatine annually. Prior research has suggested that improvements in depressive symptoms and response to antidepressants are linked to greater efficiency in brain energetics and that increased levels of brain phosphocreatine might facilitate the production of the high-energy molecule ATP. In preclinical research, creatine has shown antidepressant-like effects in female (but not male) rats. Based on these findings, investigators in Korea and Utah conducted a foundation- and government-supported, 8-week, randomized, controlled trial in which 52 otherwise medically healthy women with major depression received escitalopram (overall mean dose, 15 mg/day) plus either creatine (5 g/day) or placebo.

The groups had statistically similar rates of concomitant lorazepam and zolpidem use. Patients receiving creatine supplementation showed greater improvement than placebo recipients on the Hamilton Rating Scale for Depression (HRSD) starting by week 2; a higher response rate (≥50% reduction in HRSD scores) at weeks 2 and 4, but not later; and a higher week-8 remission rate (HRSD score, ≤7; 52% vs. 26%). Adverse events were reported by similar numbers of patients in the creatine and placebo groups.


It is unclear why only female rats showed improvement with creatine. Still, these provocative results merit extension in men and women. Creatine is to be avoided in patients with renal disease, hepatic disease, or hypertension, and it is associated with manic/hypomanic switches in depressed bipolar patients. Still, if other studies confirm the benefits, this easily available and popular supplement might prove to be a worthwhile augmentation strategy for depression — at least for women.


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