Study Overview
Citation: Toniolo RA, Fernandes FBF, Silva M, Dias RS, Lafer B. (2017).
Cognitive effects of creatine monohydrate adjunctive therapy in patients with bipolar depression: Results from a randomized, double-blind, placebo-controlled trial. Journal of Affective Disorders, 215, 108-113.
This randomised controlled trial examined creatine as an adjunct treatment for bipolar II depression — a condition characterised by depressive episodes alternating with hypomanic episodes.
It is one of the first RCTs to examine creatine’s psychiatric applications.
Study Design and Methods
The study was a randomised, double-blind, placebo-controlled trial involving patients with bipolar II disorder in a depressive episode.
Participants were already stabilised on mood stabiliser medication (lithium, valproate, or lamotrigine).
They were randomly assigned to receive either 6g/day of creatine monohydrate or placebo for 6 weeks in addition to their existing medication.
Depression severity was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HDRS).
Cognitive function was assessed using neuropsychological tests.
Key Findings
Depression Improvement
The creatine group showed significantly greater improvement in depression scores compared to placebo.
MADRS scores improved meaningfully over the 6-week treatment period, suggesting that creatine augmentation has antidepressant potential in bipolar depression.
Cognitive Benefits
Participants in the creatine group also showed improvements in verbal fluency and other cognitive measures — consistent with creatine’s established role in brain energy metabolism.
Safety Profile
Creatine was well-tolerated with no serious adverse events.
No cases of manic switching occurred during the study period, though the sample size was small and this remains a theoretical concern.
(Kreider et al., 2017)Important Caveats
- Small sample size — Larger confirmatory trials are needed
- Adjunct only — Creatine was added to existing medication, not used alone
- Bipolar II only — Results may not generalise to bipolar I disorder
- Short duration — 6 weeks may not capture long-term effects or risks
- Manic switching risk — While not observed in this study, monitoring is essential
- Not a treatment recommendation — This is preliminary research
Malaysian Relevance
Mental health treatment in Malaysia is evolving, with increasing access to psychiatric care.
For Malaysian patients with bipolar depression already under psychiatric care, this research is worth discussing with their treating psychiatrist.
Creatine supplementation should never be undertaken for psychiatric purposes without professional medical guidance.
Where This Fits in the Evidence
Toniolo and colleagues take creatine somewhere most of the literature does not go: a psychiatric clinic, testing 6g/day as an add-on to mood stabilisers in bipolar II depression rather than as a sports supplement. The improvement in MADRS scores, alongside gains in verbal fluency, fits the brain-energy rationale that runs through the cognitive side of our research library, but the trial is small and short and carries an unresolved theoretical concern about manic switching. It is best read as an early signal worth following, not a basis for treating bipolar depression with creatine. Any use here belongs under a treating psychiatrist, not self-direction.
Sources and References
- Toniolo RA, et al. (2017). Cognitive effects of creatine monohydrate adjunctive therapy in bipolar depression. JAD, 215, 108-113.
- Kreider RB, et al. (2017). ISSN position stand. JISSN, 14, 18.
What This Means for You
For anyone living with bipolar disorder, the essential point is caution: creatine here was an add-on to mood stabilisers given under close supervision, and bipolar illness carries a specific risk — the possibility of tipping a depressive phase towards hypomania — that makes unsupervised use unwise. No manic switching occurred in this small, short trial, but that risk has not been ruled out. So if the findings interest you, they are strictly something to raise with your treating psychiatrist, not to act on alone.
Further Reading
- creatine dosage guide
- creatine safety profile
- creatine monohydrate
- creatine for brain health
- how creatine works
- buying creatine in Malaysia
Sources & References
Full citations available in our Research Library.