Citation

Abdallah CG, Averill LA, Akiki TJ, Raza M, Averill CL, Gomaa H, Adikey A, Krystal JH. Annu. Rev. Pharmacol. Toxicol. 2019; 59: 171-189.

Affiliation

Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06511, USA.

Copyright

(Copyright © 2019, Annual Reviews)

DOI

10.1146/annurev-pharmtox-010818-021701

PMID

30216745

Abstract

New approaches to the neurobiology of posttraumatic stress disorder (PTSD) are needed to address the reported crisis in PTSD drug development. These new approaches may require the field to move beyond a narrow fear-based perspective, as fear-based medications have not yet demonstrated compelling efficacy. Antidepressants, particularly recent rapid-acting antidepressants, exert complex effects on brain function and structure that build on novel aspects of the biology of PTSD, including a role for stressrelated synaptic dysconnectivity in the neurobiology and treatment ofPTSD. Here, we integrate this perspective within a broader framework-in other words, a dual pathology model of (a) stress-related synaptic loss arising from amino acid-based pathology and (b) stress-related synaptic gain related to monoamine-based pathology. Then, we summarize the standard and experimental (e.g., ketamine) pharmacotherapeutic options for PTSD and discuss their putative mechanism of action and clinical efficacy. Expected final online publication date for the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Language: en