Glycine Reuptake Inhibitors in the Treatment of Negative Symptoms of Schizophrenia

Negative symptoms are present in over one quarter of patients with schizophrenia and are detrimental to prognosis, functionality and quality of life. Currently, the treatments for primary negative symptoms are inadequate. However, enhancing N-methyl-D-aspartate receptor hypofunctioning with glycine reuptake inhibitors has garnered optimism as a potential treatment. Trials of sarcosine-derivatives have yielded mixed results and potential severe side effects have halted progress to larger studies. Non- sarcosine derivatives such as bitopertin have proven to be less toxic and have shown success in phase II trials. Unfortunately, phase III trials of bitopertin to date have not met primary endpoints and a void in effective treatment options for negative symptoms persists. Further research to improve psychiatric study design, discover clinical biomarkers and build on early successes of other potential pharmacologic molecules is required.