title: Targeting cyclooxygenase-2 in depression is not a viable therapeutic approach and may even aggravate the pathophysiology underpinning depression.
abstract: Depression is a complex progressive disorder accompanied by activation of inflammatory and Th-1 driven pathways, oxidative and nitrosative stress (O&NS), lowered antioxidant levels, mitochondrial dysfunctions, neuroprogression and increased bacterial translocation. In depression, activation of immuno-inflammatory pathways is associated with an increased risk for cardio-vascular disorder (CVD). Because of the inflammatory component, the use of cyclooxygenase 2 (COX-2) inhibitors, such as celecoxib, has been advocated to treat depression. Electronic databases, i.e. PUBMED, Scopus and Google Scholar were used as sources for this selective review on the effects of COX-2 inhibitors aggravating the abovementioned pathways. COX-2 inhibitors may induce neuroinflammation, exacerbate Th1 driven responses, increase lipid peroxidation, decrease the levels of key antioxidants, damage mitochondria and aggravate neuroprogression. COX-2 inhibitors may aggravate bacterial translocation and CVD through Th1-driven mechanisms. COX-2 inhibitors may aggravate the pathophysiology of depression. Since Th1 and O&NS pathways are risk factors for CVD, the use of COX-2 inhibitors may further aggravate the increased risk for CVD in depression. Selectively targeting COX-2 may not be a viable therapeutic approach to treat depression. Multi-targeting of the different pathways that play a role in depression is more likely to yield good treatment results.
authors: Maes Clinics @ TRIA, Piyavate Hospital 998 Rimklongsamsen Road, Bangkok, 10310, Thailand. dr.michaelmaes@hotmail.com
authors: Michael
authors: M
authors: Maes
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051546:Cyclooxygenase 2