Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder

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Clonidine and guanfacine are alpha-2 receptor agonists that decrease sympathetic outflow from the central nervous system. Posttraumatic stress disorder (PTSD) is an anxiety disorder that is theorized to be related to a hyperactive sympathetic nervous system. Currently, the only US Food and Drug Administration (FDA)-approved medications for PTSD are the selective serotonin reuptake inhibitors (SSRIs) sertraline and paroxetine. Sometimes use of the SSRIs may not lead to full remission and symptoms of hyperarousal often persist. This article specifically reviews the literature on alpha-2 receptor agonist use for the treatment of PTSD and concludes that while the evidence base is limited, these agents might be considered useful when SSRIs fail to treat symptoms of agitation and hyperarousal in patients with PTSD.

Keywords: Adrenergic alpha-2 receptor agonists, anxiety disorders, clonidine, guanfacine, humans, stress disorders, posttraumatic, sympathetic nervous system, treatment outcome.

Abbreviations: ADHD, attention deficit hyperactivity disorder; APA, American Psychiatric Association; AUD, alcohol use disorder; BZD, benzodiazepine; CAPS, Clinician-Administered PTSD Scale; CNS, central nervous system; CSF, cerebrospinal fluid; EPS, extrapyramidal symptoms; FDA, Food and Drug Administration; GXR, guanfacine extended release; IES-R, Impact of Event Scale-Revised; MAOI, monoamine oxidase inhibitor; MDD, major depressive disorder; NE, norepinephrine; PTSD, posttraumatic stress disorder; SCL-90-R, Symptom Checklist-90-Revised; SNS, sympathetic nervous system; SSRI, selective serotonin reuptake inhibitors; TCA, tricyclic antidepressant; TD, tardive dyskinesia.

Citation: Belkin MR, Schwartz TL. Alpha-2 receptor agonists for the treatment of posttraumatic stress disorder. Drugs in Context 2015; 4:212286. DOI: 10.7573/dic.212286

Contributions: Thomas L Schwartz supervised the preparation of the manuscript and provided longitudinal editing. Molly Belkin provided substantial contributions to the literature review and wrote the manuscript.

Potential conflicts of interest: The International Committee of Medical Journal Editors’ (ICMJE) Potential Conflicts of Interests forms for the authors are available for download at:

Funding Declaration: The authors declare that this is an unfunded review.

Copyright: Copyright © 2015 Belkin MR, Schwartz TL. Distributed under the terms of the Creative Commons License Deed CC BY 3.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below.

Correct attribution: Copyright © 2015 Belkin MR, Schwartz TL. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 3.0.

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Correspondence: Molly R Belkin, BA, SUNY Upstate Medical University, College of Medicine, Syracuse, NY, USA.

Provenance: Submitted; externally peer reviewed

Submitted: 6 July 2015; Peer review comments to author: 17 July 2015; Published: 14 August 2015

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