EFFICACY OF ANTI-INFLAMMATORY TREATMENT ON PATIENTS WITH MOOD DISORDERS AND ELEVATED PRO-INFLAMMATORY CYTOKINE LEVELS: A 12-WEEK RANDOMIZED CONTROLLED STUDY
Authors: Bai *Ya Mei , Chen Mu Hong , Hsu Ju-Wei , Liou Ying-Jay 
Published: February 2025

Abstract

Background
There is substantial evidence supporting the pathogenic role of neuro-inflammation in mood disorders. Previous studies have shown that augmenting treatments with anti-inflammatory drugs, including aspirin and statin can lead to improved clinical outcomes for mood disorders, particularly in a subpopulation where immune dysfunction plays a significant pathogenic role. However, previous anti- inflammatory research has predominantly centered on individual drugs, lacking comparative studies.

Aims & Objectives
The objective of this 12-week randomized controlled study was to compare the efficacy of anti-inflammatory drugs, aspirin and statin, compared to the control group, among patients with mood disorders and elevated inflammatory dysregulation.

Method
This study enrolled patients diagnosed with mood disorders and exhibiting elevated levels of pro-inflammatory cytokines. According to our previous cohort of 500 subjects, we established inclusion criteria focusing on the top 30% percentile for pro- inflammatory cytokine levels. For Major Depressive Disorder (MDD) patients, the thresholds were set at soluble IL6 receptor (sIL-6) levels &gt;30000pg/ml, or C-reactive protein (CRP) levels &gt;600ng/ml, or soluble tumor necrosis factor receptor 1 (sTNF-R1) levels &gt;800pg/ml. For Bipolar Disorder (BD) patients, the thresholds were set at sIL-6 &gt;34000pg/ml, CRP &gt;1000ng/ml, or sTNF-R1 &gt;900pg/ml. While maintaining their existing medication regimen, participants were randomly assigned to one of three groups: aspirin, statin, or a control group, and received treatment for a duration of 12 weeks.

Results
We enrolled a total of 48 patients, consisting of 25 MDD and 23 BD patients. They were randomly assigned to three groups: aspirin (14 patients), statin (17 patients), and placebo (17 patients). The final results indicated significant improvements in various scales for both the aspirin and statin groups, including depressive symptoms (the Hamilton Depression Scale, HAMD, and the Montgomery-Asberg Depression Rating Scale,), anxiety symptoms (Hamilton Anxiety Rating Scale), psychotic symptoms (Positive and Negative Symptoms Scale), mental well-being (SF-36 Mental Component Scale, MCS), overall functioning (Global Assessment of Functioning Scale, GAF), and personal/social functioning (Personal and Social Function Scale), when compared to the control group. The statin group exhibited significantly greater improvements in mental well-being (SF-36 MCS) and GAF compared to the aspirin group. Regarding inflammation markers and cognitive function, no significant differences were observed among the aspirin, statin, and control groups. Further diagnostic analysis revealed that the improvement of depressive symptoms (HAMD and DSSS) with the anti-inflammatory drugs aspirin and statin was significantly more pronounced in the MDD group than in the BD group.

Discussion & Conclusion
Our study demonstrated that augmenting treatment with both aspirin and statin led to improvements in depressive, anxiety, and psychotic symptoms, as well as enhanced mental well-being, global functioning, and personal/social functioning in patients with mood disorders and elevated levels of inflammation. The statin group exhibited notably greater improvement in quality of life and global functioning. Moreover, more significant improvements in depressive symptoms were observed in MDD than BD patients.

References
MCINTYRE, R. S., SUBRAMANIAPILLAI, M., LEE, Y., PAN, Z., CARMONA, N. E., SHEKOTIKHINA, M., ROSENBLAT, J. D., BRIETZKE, E., SOCZYNSKA, J. K., COSGROVE, V. E., MILLER, S., FISCHER, E. G., KRAMER, N. E., DUNLAP, K., SUPPES, T. &MANSUR, R. B. 2019. Efficacy of Adjunctive Infliximab vs Placebo in the Treatment of Adults With Bipolar I/II Depression: A Randomized Clinical Trial. JAMA Psychiatry.
NG, Q. X., RAMAMOORTHY, K., LOKE, W., LEE, M. W. L., YEO, W. S., LIM, D. Y. &SIVALINGAM, V. 2019. Clinical Role of Aspirin in Mood Disorders: A Systematic Review. Brain Sci, 9.YATHAM, M. S., YATHAM, K. S., RAVINDRAN, A. V. &SULLIVAN, F. 2019. Do statins have an effect on depressive symptoms? A systematic review and meta-analysis. J Affect Disord, 257, 55-63.