Neurophysiological Effects of Bitopertin in Schizophrenia

J Clin Psychopharmacol. 2017 Aug;37(4):447-451. doi: 10.1097/JCP.0000000000000722.

Abstract

Purpose/background: Deficits in N-methyl-D-aspartate receptor (NMDAR) function contribute to symptoms and cognitive dysfunction in schizophrenia and are associated with impaired generation of event-related potential measures including auditory mismatch negativity. Parallel studies of the NMDAR agonist D-serine have suggested that sensitivity of these measures to glutamate-based interventions is related to symptomatic and cognitive response. Bitopertin is a selective inhibitor of glycine transport. This study investigates effects of bitopertin on NMDAR-related event-related potential deficits in schizophrenia.

Methods/procedures: Patients with schizophrenia/schizoaffective disorder were treated with bitopertin (10 mg, n = 29), in a double-blind, parallel group investigation. Auditory mismatch negativity served as primary outcome measures. Secondary measures included clinical symptoms and neurocognitive performance.

Findings/results: No significant changes were seen with bitopertin for neurophysiological, clinical, or neurocognitive assessments.

Implications/conclusions: These findings represent the first assessment of the effect of bitopertin on neurophysiological biomarkers. Bitopertin did not significantly affect either symptoms or NMDAR-related biomarkers at the dose tested (10 mg). Mismatch negativity showed high test-retest reliability, supporting its use as a target engagement measure.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Double-Blind Method
  • Female
  • Glycine Plasma Membrane Transport Proteins / antagonists & inhibitors
  • Glycine Plasma Membrane Transport Proteins / physiology
  • Humans
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Schizophrenia / diagnosis
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology*
  • Sulfones / therapeutic use*
  • Treatment Outcome

Substances

  • (4-(3-fluoro-5-trifluoromethylpyridin-2-yl)piperazin-1-yl)(5-methanesulfonyl-2-(2,2,2-trifluoro-1-methylethoxy)phenyl)methanone
  • Glycine Plasma Membrane Transport Proteins
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • SLC6A9 protein, human
  • Sulfones