4.7 Review

Targeting inflammatory pathways for treatment of the major depressive disorder

Journal

DRUG DISCOVERY TODAY
Volume 28, Issue 9, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.drudis.2023.103697

Keywords

astrocytes; depression; in flammation; kinins; TNF-a

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Current treatments for major depressive disorder primarily focus on targeting the monoaminergic neurotransmission. However, limitations in efficacy and adverse effects restrict the use of conventional antidepressants to a limited subset of patients. The inefficacy of classical antidepressants in treating treatment-resistant depression has shifted the focus to alternative pathogenic pathways, particularly immuno-inflammatory pathways. This review highlights the connection between inflammatory pathways and major depressive disorder and examines the current clinical status of inflammation-modulating drugs in its treatment.
Current treatments modalities for major depressive disorder (MDD) mainly target the monoaminergic neurotransmission. However, the therapeutic inadequacy and adverse effects confine the use of these conventional antidepressants to a limited subset of MDD patients. The classical antidepressants are increasingly proving unsatisfactory in tackling the treatment-resistant depression (TRD). Hence, the focus of treatment is shifting to alternative pathogenic pathways involved in depression. Preclinical and clinical evidences accumulated across the last decades have unequivocally affirmed the causative role of immuno-inflammatory pathways in the progression of depression. There is an upsurge in the clinical evaluations of the drugs having anti-inflammatory effects as antidepressants. This review highlights the molecular mechanisms connecting the inflammatory pathways to the MDD and current clinical status of inflammation modulating drugs in the treatment of MDD.

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