This study investigated whether aspirin and atorvastatin provide additional antidepressant effects in patients with major affective disorders and inflammatory dysregulation.

Three 12-week treatment groups, each receiving aspirin (100 mg/day), atorvastatin (10 mg/day), or a placebo, were randomly assigned to 14 patients (seven with major depressive disorder [MDD] and seven with bipolar disorder [BD]), as well as two additional groups of 17 patients (each with nine patients with MDD and eight patients with BD). All patients had Clinical Global Impressions scores ≤3 and met the criteria for inflammatory dysregulation (i.e., C-reactive protein (CRP) level ≥ 1,000 ng/ml or soluble tumor necrosis factor-α receptor 1 (TNF-αR1) level ≥ 800 pg/ml). The Hamilton Depression Rating Scale (HDRS) and Montgomery-Sberg Depression Rating Scale (MADRS) were used to assess depressive symptoms, and the Global Assessment of Functioning Scale (GAF) was used to assess overall functioning. Baseline and week 12 CRP, TNF-αR1, and soluble IL-2 receptor (sIL-2R) levels were evaluated.

Generalized estimating equation models demonstrated a reduction in total HDRS (p < 0.001) and MADRS (p < 0.001) scores and an increase in GAF scores (p < 0.001) in the medication groups compared with the placebo group. Only atorvastatin increased anti-inflammatory cytokine sIL-2R levels (p < 0.001). Both atorvastatin (p < 0.001) and aspirin (p = 0.025) raised proinflammatory cytokine sTNF-αR1 levels.

Aspirin and atorvastatin improved depressive symptoms and overall function in patients with major affective disorders. However, both medications raised TNF-αR1 levels, and only atorvastatin increased sIL-2R levels.