5-HT2 ligands in the treatment of anxiety and depression

Introduction: One third of depressed patients do not respond adequately to conventional antidepressants including the selective serotonin reuptake inhibitors (SSRIs). Therefore, multi-target drugs or augmentation strategies have been developed for the management of SSRIs-resistant patients. In this context, the 5-HT2 receptor subtypes represent promising targets but their precise roles have yet to be determined. Areas covered: The aim of this review is to shed some light on the preclinical evidence supporting the use of 5-HT2A and/or 5-HT2C receptor antagonists such as antipsychotics, as potential effective adjuncts in SSRIs-resistant depression. This review synthesizes the current literature about the behavioral, electrophysiological and neurochemical effects of 5-HT2 receptors ligands on the monoaminergic systems but also on adult hippocampal neurogenesis. Expert opinion: Although studies support the hypothesis that the inactivation of 5-HT2A and/or 5-HT2C receptors might be of interest to reinforce dif...