The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder

Annu Rev Pharmacol Toxicol. 2019 Jan 6:59:171-189. doi: 10.1146/annurev-pharmtox-010818-021701. Epub 2018 Sep 14.

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 stress-related synaptic dysconnectivity in the neurobiology and treatment of PTSD. 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.

Keywords: PTSD; RAAD; antidepressant; chronic stress; ketamine; posttraumatic stress disorder; rapid-acting antidepressant; trauma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Brain / drug effects
  • Brain / physiopathology
  • Humans
  • Stress Disorders, Post-Traumatic / drug therapy*
  • Stress Disorders, Post-Traumatic / physiopathology*

Substances

  • Antidepressive Agents