Creatine and depression?

Creatine supplementation shows promising effects for treating depression, particularly when used to augment the response to selective serotonin re-uptake inhibitors (SSRIs). Studies have found that creatine can either lower the required dose of SSRIs or enhance their effectiveness. This effect has been particularly noted in women with major depressive disorder. Further, creatine increases the activity of the phosphocreatine system in the forebrain, which may influence the function of NMDA receptors. These receptors are involved in neuroplasticity and are critical in the neural circuitry changes that shift mood from negative to positive 1.

Additionally, creatine supplementation has been shown to increase mood activation, which could be beneficial for those with low affect and major depression. However, it's important to consult with a healthcare provider before starting supplementation, particularly for individuals experiencing manic phases because creatine can increase mania 2.