Cool the Inflamed Brain: A Novel Anti-inflammatory Strategy for the Treatment of Major Depressive Disorder

Abstract

Background: Abundant evidence suggests that inflammatory cytokines contribute to the symptoms of major depressive disorder (MDD) by altering neurotransmission, neuroplasticity, and neu-roendocrine processes. Given the unsatisfactory response and remission of monoaminergic antidepres-sants, anti-inflammatory therapy is proposed as a feasible way to augment the antidepressant effect. Recently, there have been emerging studies investigating the efficiency and efficacy of anti-inflammatory agents in the treatment of MDD and depressive symptoms comorbid with somatic diseases. Methods: In this narrative review, prospective clinical trials focusing on anti-inflammatory treatment for depression have been comprehensively searched and screened. Based on the included studies, we summarize the rationale for the anti-inflammatory therapy of depression and discuss the utilities and confusions regarding the anti-inflammatory strategy for MDD. Results: This review included over 45 eligible trials. For ease of discussion, we have grouped them into six categories based on their mechanism of action, and added some other anti-inflammatory modalities, including Chinese herbal medicine and non-drug therapy. Pooled results suggest that anti-inflammatory therapy is effective in improving depressive symptoms, whether used as monotherapy or add-on therapy. However, there remain confusions in the application of anti-inflammatory therapy for MDD. Conclusion: Based on current clinical evidence, anti-inflammatory therapy is a promisingly effective treatment for depression. This study proposes a novel strategy for clinical diagnosis, disease classifica- tion, personalized treatment, and prognostic prediction of depression. Inflammatory biomarkers are recommended to be assessed at the first admission of MDD patients, and anti-inflammatory therapy are recommended to be included in the clinical practice guidelines for diagnosis and treatment. Those patients with high levels of baseline inflammation (e.g., CRP > 3 mg/L) may benefit from adjunctive anti-inflammatory therapy.

Thematic Selection: Stress and Stress-related Disorders Neurobiology & Translational Aspects of Stress-related Disorders (Part 3)

“…In two clinically relevant reviews, Su et al provided an interesting overview of prospective clinical trials on promising novel anti-inflammatory strategies for the treatment of major depressive disorder (MDD) [ 4 ], while Menke reviewed promising study results of MDD treatment alternatives targeting the hypothalamic-pituitary-adrenal axis, such as corticotrophin-releasing hormone 1, vasopressin V1B and glucocorticoid receptor antagonists as well as FKBP5 antagonists [ 5 ].…”