Rapastinel - an investigational NMDA-R modulator for major depressive disorder: evidence to date

Introduction: Major depressive disorder (MDD) is a debilitating disorder with increasing prevalence globally. Despite the development of novel treatments for MDD, many patients present with treatment resistant depression (TRD), identified by treatment non-response following one or more adequate trials of an antidepressant. Rapastinel may prove to be a viable treatment for TRD; it has the potential to produce a rapid antidepressant response without serious adverse events and improve functional symptoms.Areas covered: We review the efficacy of rapastinel via completed and on-going clinical trials. The online databases Pubmed, clinicaltrials.gov and clinicaltrialsregister.eu were searched for rapastinel (GLYX-13) treatment in subjects with MDD. Nine clinical trials were identified.Expert opinion: Rapastinel is a novel and potentially transformative treatment for individuals with TRD. There is a limited number of clinical studies so far, but this compound has the potential to provide rapid, reliable and robust antidepressant effects without psychotomimetic and other unwanted side effects. Alternative formulations such as the oral formulation, provide the opportunity for rapastinel to be administered less frequently, i.e. once weekly. Furthermore, the beneficial effects on measures of cognition and suicidality so far, represent a tremendous advantage.