Serendipity led to the discovery of antipsychotic medications, which are the cornerstone of acute and maintenance treatment for schizophrenia.1 Unfortunately, these drugs lack efficacy in alleviating negative symptoms and cognitive symptoms. Notwithstanding the substantial advances in our mechanistic understanding of this phenotypically complex syndrome in the decades since their discovery, efforts to translate scientific progress into novel treatments that will address different schizophrenia symptoms dimensions have been largely unsuccessful.2 Perhaps the greatest disappointments in recent memory have been the traditional multisite clinical trials of several glutamate-based treatments for schizophrenia, which garnered negative results despite a large body of theoretical and experimental evidence indicating that glutamatergic dysfunction is a core feature of the disease.2
Kraguljac NV, Lahti AC. Paving the Way for Targeted Drug Development in Schizophrenia. JAMA Psychiatry. 2018;75(1):19–20. doi:10.1001/jamapsychiatry.2017.3501
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