The Neurobiology and Pharmacotherapy of Posttraumatic Stress Disorder.
Chadi G. Abdallah, Lynnette A. Averill, Teddy J. Akiki, Mohsin Raza, Christopher L. Averill, Hassaan Gomaa, Archana Adikey, John H. Krystal
The Annual Review of Pharmacology and Toxicology September 14, 2018 DOI: 10.1146/annurev-pharmtox-010818-021701 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Theoretical or philosophical paper Peer reviewed |
|---|---|
| Topics | Ketamine PTSD |
| Keywords | Brain Animals Humans Antidepressive agents Stress disorders, post-traumatic Chronic stress Posttraumatic stress disorder Rapid-acting antidepressant Raad |
| Key points | Argues that PTSD drug development should move beyond a fear-based framework because fear-based medications have not demonstrated compelling efficacy, and proposes a "dual pathology model" combining stress-related synaptic loss from amino acid-based pathology with stress-related synaptic gain from monoamine-based pathology. The authors contend that antidepressants, particularly rapid-acting agents such as ketamine, act on this biology through effects on brain function and structure, and they review standard and experimental PTSD pharmacotherapies and their proposed mechanisms and clinical efficacy. |
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.
Comparable studies
Other theoretical and historical papers on ketamine for PTSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ketamine-Prazosin Combined Pharmacotherapy in Post-Traumatic Stress Disorder and Alcohol Use Disorder: Targeting Complementary Neurobiological Mechanisms. Not specified | 2026 | Theoretical or philosophical paper | |
| Psychoplastogens: A Promising Class of Plasticity-Promoting Neurotherapeutics. | 2018 | Theoretical or philosophical paper |
Citations in the library
Cited by 19
- Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review. Current Neuropharmacology 2024
- Modulation of the antidepressant effects of ketamine by the mTORC1 inhibitor rapamycin Neuropsychopharmacology February 24, 2020
- The potential of ketamine for posttraumatic stress disorder: a review of clinical evidence. Therapeutic Advances in Psychopharmacology 2023
- A proposed mechanism for the MDMA-mediated extinction of traumatic memories in PTSD patients treated with MDMA-assisted therapy Frontiers in Psychiatry October 12, 2022
- The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics. Neurochemical Research April 1, 2023
and 14 more in the library
Cites 20
- Synaptic Dysfunction in Depression: Potential Therapeutic Targets Science October 4, 2012
- The salience network is responsible for switching between the default mode network and the central executive network: Replication from DCM Neuroimage May 24, 2014
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Ketamine for rapid reduction of suicidal thoughts in major depression: a midazolam-controlled randomized clinical trial American Journal of Psychiatry December 5, 2017
and 15 more in the library