title: A critical review of the mechanism of action for the selective serotonin reuptake inhibitors: do these drugs possess anti-inflammatory properties and how relevant is this in the treatment of depression?
abstract: The selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed pharmacological treatment for depression. Since their introduction many have considered the primary mechanism by which the SSRIs produced therapeutic improvement in depression is their effect on monoaminergic signalling. In recent years, however, the credibility of the monoamine theory and the therapeutic efficacy of these compounds in the treatment of depression has been extensively criticized. In the current review the legitimacy of these criticisms is critically examined, in many instances the evidence base used to support these criticisms is found to be weak. Nevertheless, the apparent 'failure' of the monoamine theory has been of benefit in motivating research into alternative mechanisms through which the SSRIs may act. Given research demonstrating that depressive symptoms are intimately linked with disturbances in pro-inflammatory signalling, perhaps the most promising discovery has been the realisation that SSRIs posses significant anti-inflammatory properties. These recent findings are discussed and contextualised with respect to the neurogenic, neurotrophic and gluatamatergic effects that these drugs also possess.
authors.affiliation: Laboratory of Affective Neuroscience and Neuroimmunology, School of Biomedical Sciences and Pharmacy, Priority Research Centre for Brain and Mental Health, Hunter Medical Research Institute, University of Newcastle, Callaghan, NSW 2308, Australia. rohan.walker@newcastle.edu.au
authors.forename: Frederick Rohan
authors.initials: FR
authors.lastname: Walker
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000453:epidemiology / Q000523:psychology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000453:epidemiology / Q000523:psychology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D017367:Selective Serotonin Reuptake Inhibitors