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- W2149678857 abstract "All antipsychotics approved by the U.S. Food and Drug Administration for the treatment of schizophrenia act primarily to reduce the stimulation of dopamine D2 receptors. This finding would seem to imply that all patients, or perhaps just patients who are responsive to pharmacotherapy, manifest overstimulation of D2 receptors by dopamine ( 1 Frankle W.G. Gil R. Hackett E. Mawlawi O. Zea-Ponce Y. Zhu Z. et al. Occupancy of dopamine D2 receptors by the atypical antipsychotic drugs risperidone and olanzapine: Theoretical implications. Psychopharmacology (Berl). 2004; 175: 473-480 PubMed Google Scholar ). It also reflects a failure of medication development efforts to address adequately the heterogeneous pathophysiologies associated with schizophrenia. Given recent prominence of the hypothesis that early intervention may lead to better long-term outcomes, it may be timely to draw attention to one potential source of heterogeneity within and across patients—the dynamic time-dependent neurobiological evolution of schizophrenia across its course of illness. This interest is further fueled by an article in this issue of Biological Psychiatry, which suggests that patients early in their course of illness respond favorably to monotherapy with pomaglumetad methionil, a drug that is metabolized into an agonist of metabotropic glutamate 2/3 (mGluR2/3) receptor. The article also reports the provocative finding that the same drug is not only ineffective but also may worsen clinical outcomes for patients with long-standing illness ( 2 Kinon B.J. Millen B.A. Zhang L. McKinzie D.L. Exploratory analysis for a targeted patient population responsive to the metabotropic glutamate 2/3 receptor agonist pomaglumetad methionil in schizophrenia. Biol Psychiatry. 2015; 78: 754-762 Abstract Full Text Full Text PDF PubMed Scopus (109) Google Scholar ). Although the article presents results supporting alternative hypotheses, the focus of this commentary is on the possible implications for illness phase–specific pharmacotherapies." @default.
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- W2149678857 date "2015-12-01" @default.
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- W2149678857 title "Toward Illness Phase–Specific Pharmacotherapy for Schizophrenia" @default.
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- W2149678857 doi "https://doi.org/10.1016/j.biopsych.2015.08.017" @default.
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