Emerging drugs for the treatment of anxiety

Abstract

Introduction: Anxiety disorders are among the most prevalent and disabling psychiatric disorders in the United States and worldwide. Basic research has provided critical insights into the mechanism regulating fear behavior in animals and a host of animal models have been developed in order to screen compounds for anxiolytic properties. Despite this progress, no mechanistically novel agents for the treatment of anxiety have come to market in more than two decades.

Areas covered: The current review will provide a critical summary of current pharmacological approaches to the treatment of anxiety and will examine the pharmacotherapeutic pipeline for treatments in development. Anxiety and related disorders considered herein include panic disorder, social anxiety disorder, generalized anxiety disorder and post-traumatic stress disorder. The glutamate, neuropeptide and endocannabinoid systems show particular promise as future targets for novel drug development.

Expert opinion: In the face of an ever-growing understanding of fear-related behavior, the field awaits the translation of this research into mechanistically novel treatments. Obstacles will be overcome through close collaboration between basic and clinical researchers with the goal of aligning valid endophenotypes of human anxiety disorders with improved animal models. Novel approaches are needed to move basic discoveries into new, more effective treatments for our patients.

Keywords:

• anxiety
• anxiolytic
• clinical trial
• endocannabinoid
• glutamate
• neuropeptide
• panic disorder
• posttraumatic stress disorder

Declaration of interest

In the past 3 years, JW Murrough has served on advisory boards for Janssen Research and Development and Genentech, has provided consultation services for ProPhase, LLC and Impel Neuropharma and has received research support from Janssen and Avanir Pharmaceuticals; he is named on a patent pending for neuropeptide Y as a treatment for mood and anxiety disorders; he is named on a patent pending for lithium as a method to maintain the antidepressant response to ketamine. DS Charney (Dean of Icahn School of Medicine at Mount Sinai), and Icahn School of Medicine at Mount Sinai has been named on a use patent on ketamine for the treatment of depression. The Icahn School of Medicine has entered into a licensing agreement for the use of ketamine as therapy for treatment-resistant depression. DS Charney and Icahn School of Medicine at Mount Sinai could potentially benefit if ketamine were to gain approval for the treatment of depression. DS Charney is named on a patent pending for ketamine as a treatment for PTSD and for neuropeptide Y as a treatment for mood and anxiety disorders; he has received funding from the U.S. Department of Defense, NIH, NIH/NIMH, NARSAD, USAMRAA; he has severed on the scientific advisory board for the Institute of Medicine Committee on DHS Workforce Resilience and on the editorial board of CNS Spectrums. JW Murrough is supported by NIH grant K23MH094707 and by the Doris Duke Charitable Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.