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anti-inflammatory→HPA axis→serotonin modulation
Statins may exert antidepressant effects via anti-inflammatory mechanisms (reducing IL-6, TNF-α), antioxidant activity, and modulation of the HPA axis and serotonergic systems. Evidence includes small placebo-controlled RCTs as add-on to SSRIs and a meta-analysis of RCTs, providing moderate clinical support. This is an active research area but not yet established clinical practice.
“Three small placebo-controlled trials conducted in Iran (total N=172) have found that statins as add-on to selective serotonin reuptake inhibitors (SSRIs) have antidepressant effects in patients with major depressive disorder (MDD).”
— Statins in the treatment of depression: Hype or hope? (2020)DOI“This review provides an overview of this field by reviewing the following aspects: 1) Candidate mechanisms that could mediate putative antidepressant effects of statins; 2) The evidence for and against antidepressant effects of statins in patients with major depressive disorder and among individuals”
— Statins in the treatment of depression: Hype or hope? (2020)DOI“Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.”
— Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials. (2021)DOI“Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance.”
— Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder. (2022)DOI“This systematic review suggests the efficacy, acceptability, tolerability, and safety of statins in addition to antidepressants in patients with major depressive disorder.”
— Statins for major depressive disorder: A systematic review and meta-analysis of randomized controlled trials. (2021)DOI“Therefore, we aimed to evaluate the effects of statin on depressive mood and inflammation status among MDD patients.”
— Statin for mood and inflammation among adult patients with major depressive disorder: an updated meta-analysis. (2023)DOI