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 posttraumatic 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.

Traumatic experiences can lead to a range of mental health problems with posttraumatic stress disorder (PTSD) leading as the most documented disorder following trauma. Epidemiological research has found the rate of exposure to trauma to far outweigh the prevalence of PTSD. Indicating that most people do not develop PTSD following a traumatic event, this phenomenon has led to an interest in evaluating risk factors to determine who develops PTSD. Risk factors for the development of psychopathology following trauma exposure fall into three categories: pre-trauma, peri-trauma and post-trauma factors. Pre-trauma factors can include age, gender, race/ethnicity, education, prior psychopathology, and neurobiological factors. Peri-trauma factors can include the duration/severity of trauma experience and the perception that the trauma has ended. Post-trauma factors can include access to needed resources, social support, specific cognitive patterns, and physical activity. To date, several important risk factors have been found to impact the risk of developing PTSD including gender, age, education, IQ, race and ethnicity, sexual orientation, pre-trauma psychopathology, prior trauma exposure, familial psychiatric history, and neurobiological factors. This article outlines the state of research findings on pretraumatic, peritraumatic, and posttraumatic risk factors for the development of PTSD and associated psychopathology following trauma.

BackgroundAnxiety and trauma-related disorders are among the most prevalent and disabling medical conditions in the United States, and posttraumatic stress disorder in particular exacts a tremendous public health toll. We examined the tolerability and anxiolytic efficacy of neuropeptide Y administered via an intranasal route in patients with posttraumatic stress disorder.MethodsTwenty-six individuals were randomized in a cross-over, single ascending dose study into 1 of 5 cohorts: 1.4 mg (n=3), 2.8 mg (n=6), 4.6 mg (n=5), 6.8 mg (n=6), and 9.6 mg (n=6). Each individual was dosed with neuropeptide Y or placebo on separate treatment days 1 week apart in random order under double-blind conditions. Assessments were conducted at baseline and following a trauma script symptom provocation procedure subsequent to dosing. Occurrence of adverse events represented the primary tolerability outcome. The difference between treatment conditions on anxiety as measured by the Beck Anxiety Inventory and the State-Trait Anxiety Inventory immediately following the trauma script represented efficacy outcomes.ResultsTwenty-four individuals completed both treatment days. Neuropeptide Y was well tolerated up to and including the highest dose. There was a significant interaction between treatment and dose; higher doses of neuropeptide Y were associated with a greater treatment effect, favoring neuropeptide Y over placebo on Beck Anxiety Inventory score (F1,20=4.95, P=.038). There was no significant interaction for State-Trait Anxiety Inventory score.ConclusionsOur study suggests that a single dose of neuropeptide Y is well tolerated up to 9.6 mg and may be associated with anxiolytic effects. Future studies exploring the safety and efficacy of neuropeptide Y in stress-related disorders are warranted.The reported study is registered at: http://clinicaltrials.gov (ID: NCT01533519).

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