title: The role of GABA-A receptor in the synergism between SSRI and antipsychotic in schizophrenia; implications for antipsychotic modes of actions.
abstract: Antipsychotics, old and new varieties, are effective against positive symptoms such as hallucination and delusions, but are often of limited value in treating core features of schizophrenia particularly negative symptoms. Developments of new drugs based on current dogmas have produced similar drugs with no breakthroughs in effectiveness. New knowledge as to which mechanisms are responsible for symptom productions and treatment is needed. There is evidence that response may improve when antipsychotics are augmented with selective serotonin reuptake inhibitor (SSRI). This augmenting effect cannot be explained by summating pharmacological effects of the individual drugs. In a series of laboratory and clinical studies, we identified unique biochemical effects of the SSRI-Antipsychotic combination, different from each individual drug and suggested that some of these may mediate the clinical effect. In this paper, we review these studies and propose that modulation of the gamma-aminobutyric acid (GABA)-A receptor and its regulating system is the mechanism by which SSRI antipsychotic synergism exerts its clinical efficacy.
authors.affiliation: Molecular Neuropsychiatry Unit, Brain Behavior Laboratory, Technion-Faculty of Medicine, Haifa, Israel. mdsilver@tx.technion.ac.il
authors.forename: Henry
authors.initials: H
authors.lastname: Silver
authors.forename: Reef
authors.initials: R
authors.lastname: Einoch
authors.forename: Moussa
authors.initials: M
authors.lastname: Youdim
authors.forename: Orly
authors.initials: O
authors.lastname: Weinreb
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D011963:Receptors, GABA-A / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy*; D017367:Selective Serotonin Reuptake Inhibitors / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D011963:Receptors, GABA-A; D017367:Selective Serotonin Reuptake Inhibitors