Creatine supplementation → Depression
Higher Creatine supplementation moves Depression only in some conditions. Read the mechanism.
Toniolo 2019 found that 6 g a day of creatine monohydrate as an add-on for six weeks did not beat placebo on the change in Montgomery-Åsberg score among 35 people already treated for a bipolar depressive episode (P=0.560), while a secondary remission cut (score of 12 or less) favored creatine (52.9 percent versus 11.1 percent).
Randomized trial · Contested · N=35
Supported by an experiment or a tightly identified design. Read the caveats.
Mechanism
The authors treat creatine as a mitochondrial add-on in bipolar depression, not as a treatment for ordinary major depression. People stayed on their usual mood drugs. Toniolo, Silva, Fernandes, Amaral, Dias and Lafer (2019) assigned 35 adults with DSM-IV bipolar I or II in a depressive episode to 6 g a day of creatine monohydrate or placebo for six weeks, on top of regular medication. The primary was change in MADRS. Intention-to-treat, the groups did not differ (P=0.560, Cohen's d=0.231). Remission, defined as MADRS of 12 or less at week 6, was 52.9 percent on creatine and 11.1 percent on placebo among the 35 randomized (odds ratio 9.0, P=0.012). Among 23 completers it was 66.7 versus 18.2 percent. Two people on creatine switched to hypomania or mania early.
Caveats
Researchers assigned people to a powder or a control, so this is a trial stamp. This is bipolar depression as an adjunct, not unipolar major depression as a sole treatment. More papers of the same design do not settle the claim. The primary MADRS change missed. Remission is a secondary cut on thirty-five people. Two early polarity switches sit on the creatine arm. That is why the sign is context-dependent and the confidence is contested. The sister file is verbal fluency in the same trial. It hangs on the creatine-and-cognition page, not here. This is a journal entry, not medical advice and not a reason to add creatine to a mood prescription.
Effect
qualitative. Toniolo 2019 bipolar adjunct. MADRS change ITT P=0.560, d=0.231 NS. Remission MADRS<=12: 52.9% vs 11.1% ITT, OR 9.0, P=0.012. N=35. Two hypomania/mania switches on creatine.
Nodes
Named confounders
Cite this page
What Causes What. “Creatine supplementation → Depression.” https://whatcauseswhat.org/edges/e-creatine-depression (atlas updated 2026-09-02).
Papers
- A randomized, double-blind, placebo-controlled, proof-of-concept trial of creatine monohydrate as adjunctive treatment for bipolar depression.
RA Toniolo, M Silva, FBF Fernandes, JAMS Amaral, RDS Dias, B Lafer · 2019 · Journal of neural transmission (Vienna, Austria : 1996)