New Drug Therapies May Be Effective for Schizophrenia Treatment

With many new drug therapies targeting the brain’s glutamate pathway—disturbances of which can contribute to symptoms of schizophrenia—a new study finds that at least 1 of these therapies could be an effective way to treat individuals in the earlier stages of the disease.

Noting that accumulating evidence suggests that glutamatergic tone in schizophrenia may vary as a function of illness duration or medication history, researchers conducted an exploratory analysis of the existing clinical trial database of pomaglumetad methionil (pomaglumetad) in an effort to demonstrate treatment response in targeted patient populations.
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A team of investigators summarized results of the H8Y-MC-HBBM study and an integrated analysis based on 5 placeo-controlled trials. The researchers randomly assigned patients with schizophrenia to receive either pomaglumetad, 40 or 80 mg twice daily (BID); a placebo; or risperidone, 2 mg BID, for up to 6 weeks. Patient subgroups were analyzed to determine the efficacy of pomaglumetad treatment in patients early-in-disease and late-in-disease, and in those previously treated with central nervous system drugs with prominent serotonin 2A receptor antagonist activity or with predominant dopamine D2 receptor antagonist activity.

In the HBBM study and integrated analysis, the team found that only patients that were early-in-disease or previously treated with D2 drugs showed considerably greater improvement in comparison to those receiving placebo, when treated with pomaglumetad, 40 mg—but not 80 mg—BID. The authors note that treatment response to risperidone “did not appear to depend upon these patient subgroups.”

Ultimately, “demonstration of antipsychotic efficacy of a potential glutamate-based pharmacotherapy for schizophrenia may require the identification of appropriate patient subgroups whose treatment responsiveness may be fundamentally related to dysregulation of central nervous system glutamatergic tone,” according to the authors.

—Mark McGraw

Reference

Kinon B, Millen B, et al. Exploratory Analysis for a Targeted Patient Population Responsive to the Metabotropic Glutamate 2/3 Receptor Agonist Pomaglumetad Methionil in Schizophrenia. Biological Psychiatry. 2015.