New drug therapies that target glutamate pathway may be effective for subgroups of patient with schizophrenia

Mounting evidence indicates that disturbances in the brain's glutamate pathway contribute to symptoms of schizophrenia. Thus, the glutamate pathway has become the target of a number of new drug therapies. Findings published in the journal Biological Psychiatry suggest that at least one of these drugs may be an effective treatment for individuals in the early course of the illness.

Re-analyzed data from inconclusive clinical trials of a compound called pomaglumetad methionil suggest that a more targeted population of subjects--patients who are early-in-disease or patients who have not already been exposed to other antipsychotic medications--may have produced a statistically significant response.

The authors of the current study hypothesize that these previous trials may have inadvertently selected subjects who would be nonresponsive to the medication and conclude that future efficacy trials may require the identification of subgroups of patient populations.

"The complex pathophysiology of schizophrenia and resultant patient heterogeneity present significant challenges to developing new and effective therapies for this disorder," said corresponding author Dr. Bruce Kinon of Lundbeck LLC. "Receptor selective compounds such as pomaglumetad may target specific sites that mediate disease in some but not all patients. Our tentative, though testable, findings may provide a direction for the development of personalized treatments for a patient subgroup whose illness is associated with a dysregulation of brain glutamate function."

"As we develop drugs that work by targeting the primary brain pathology in schizophrenia, it is likely that the differences between patients are going to play a bigger role in determining optimal treatment," commented Dr. John Krystal, Editor of Biological Psychiatry. "Kinon and his colleagues present interesting data suggesting that although pomaglumetad methionil does not work for all patients, it may be helpful for patients early in their course of illness or who have not had extensive prior treatment with a second generation antipsychotic medication or other serotonin-2 receptor antagonist."