The harsh reality: Despite all the medications available today, approximately 30% of people with depression remain treatment-resistant. Could a common sports supplement offer new hope?
The Creatine Connection
Most fitness enthusiasts know creatine as a powerful supplement for improving athletic performance. It enhances strength and stamina by increasing energy production through ATP – our body’s primary energy currency.
But what if this same energy-boosting mechanism could help tackle depression?
Rethinking Depression: Beyond Neurotransmitters
For decades, the dominant hypothesis has been that depression stems from deficiencies in neurotransmitters like serotonin and dopamine. This is why selective serotonin reuptake inhibitors (SSRIs) have become the standard treatment – they aim to increase the availability of these crucial mood-regulating chemicals.
However, there’s a critical piece often overlooked: producing these neurotransmitters requires energy (ATP).
Recent research has revealed that depression may actually be linked to impaired energy metabolism in the brain. This groundbreaking insight suggests that by increasing energy production, creatine might enable the brain to produce more serotonin and dopamine, potentially improving mood and alleviating depressive symptoms.
What the Research Shows
Creatine + Antidepressants
In a pivotal proof-of-concept study published in the American Journal of Psychiatry, women with major depressive disorder who received 5g of creatine daily alongside Escitalopram (the SSRI marketed as Lexapro) experienced faster symptom relief compared to those taking the antidepressant alone.
Multiple smaller studies have since confirmed this pattern: when combined with SSRIs, creatine appears to enhance therapeutic outcomes for depression.
Creatine + Therapy
Perhaps even more exciting is creatine’s potential alongside non-pharmaceutical interventions. Cognitive Behavioral Therapy (CBT) is a frontline treatment for depression, helping patients identify and reshape negative thought patterns.
A 2025 double-blind, randomized controlled trial led by Sherpa and colleagues tested this combination. The study included 100 participants with clinical depression in India, divided into two groups:
- One receiving CBT plus 5g of creatine daily
- Another receiving CBT plus a placebo
After 8 weeks, both groups showed improvements, but the creatine group demonstrated statistically significantly greater reductions in depression symptoms.
Beyond Depression: Creatine’s Broader Benefits
Creatine’s potential impact extends beyond mood regulation. Research has consistently demonstrated its effectiveness for:
- Enhancing cognitive function and memory
- Increasing muscle strength and power
- Supporting overall brain health
- Improving exercise recovery
All of this comes with a remarkably clean safety profile and at a surprisingly low cost.
The Bottom Line
While research is still emerging, early studies look extremely promising for creatine as a complementary treatment for depression, whether used alongside SSRIs or cognitive behavioral therapy.
Given its well-established safety profile, affordable price point, and multiple health benefits, incorporating 5g of creatine monohydrate into your daily routine could be a wise investment in your overall wellbeing.
Important note: The studies referenced used creatine monohydrate specifically, so stick with this form for evidence-based results.
References
- Lyoo IK, Yoon S, Kim TS, et al. 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. Am J Psychiatry. 2012;169(9):937-945. doi:10.1176/appi.ajp.2012.12010009
- Sherpa NN, De Giorgi R, Ostinelli EG, Choudhury A, Dolma T, Dorjee S. Efficacy and safety profile of oral creatine monohydrate in add-on to cognitive-behavioural therapy in depression: An 8-week pilot, double-blind, randomised, placebo-controlled feasibility and exploratory trial in an under-resourced area. Eur Neuropsychopharmacol. 2025;90:28-35. doi:10.1016/j.euroneuro.2024.10.004
