The Social Brain, Stress, and Psychopathology

these domains are prominent with NMDA-channel blockade. As a phase 2 exploratory study, these results are quite encouraging and consistent with a priori hypotheses. And now the bad news. On January 21, 2014, Roche announced that 2 phase 3 trials of bitopertin for negative symptoms failed to achieve primary endpoints. Once again,we are faced with the dilemma of an initial rigorous trial providing support for a compound that is well grounded in preclinical andclinical studies, followedbya failure to replicate.Wemust wait until more information is available about the more recentnegativestudies todeterminewhether the failure to replicate can be understood by aspects of study design or implementation or by participant heterogeneity. It is clear that advances in basic neuroscience and drug developmentmust be matched by improved clinical trial methods including identificationofbiomarkers to reduce theproblemofpatientheterogeneity. Otherwise, promising new agents associated with moderate therapeutic effects may be abandoned despite the potential for largeandconsistenteffects if apersonalizedmedicine approach can be achieved.