Chapter 3.5 Atypical antipsychotic drugs and stress
Both preclinical and clinical evidence suggest that atypical antipsychotics may modulate the stress response in a manner that is distinct from conventional agents. For example, atypical antipsychotics have anxiolytic-like actions in a number of animal models. The mechanisms underlying these anxiolytic effects are not clear, but it is possible that antipsychotic-induced alterations in GABAergic neurosteroids play a role. Atypical antipsychotics also demonstrate unique effects in prefrontal cortex stress paradigms focusing on dopamine alterations. Data that mild stress also increases extracellular GABA levels in prefrontal cortex but not striatum, with no concurrent effects on glycine levels is presented. Neurosteroids may be relevant to these prefrontal cortex investigations. The authors review the emerging stress-modulatory profile of atypical antipsychotics and discuss potential ramifications of these findings for the therapeutic efficacy of these compounds. In addition to their well-established roles in the treatment of schizophrenia core symptoms, atypical antipsychotics also have utility in the treatment of depression- and anxiety-spectrum symptoms that frequently accompany the illness. Atypical antipsychotics also appear to have efficacy in the treatment of stress-sensitive anxiety disorders such as post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), underscoring the possibility that these agents may have stress-modulatory actions that are clinically therapeutic. As the knowledge of the stress-modulatory actions of atypical antipsychotics evolves, it may be possible to target these properties in the development of novel agents in the treatment of schizophrenia and other psychiatric disorders. © 2005 Elsevier B.V. All rights reserved.
Marx, CE; Grobin, AC; Deutch, AY; Lieberman, JA
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