Abstract
Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. While there continues to be expansive research in posttraumatic stress disorder (PTSD), depression and schizophrenia, there is a relative dearth of novel medications under investigation for anxiety disorders. This review's first aim is to summarize current pharmacological treatments (both approved and off-label) for panic disorder (PD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and specific phobias (SP), including selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones (e.g., buspirone), mixed antidepressants (e.g., mirtazapine), antipsychotics, antihistamines (e.g., hydroxyzine), alpha- and beta-adrenergic medications (e.g., propranolol, clonidine), and GABAergic medications (benzodiazepines, pregabalin, and gabapentin). Posttraumatic stress disorder and obsessive-compulsive disorder are excluded from this review. Second, we will review novel pharmacotherapeutic agents under investigation for the treatment of anxiety disorders in adults. The pathways and neurotransmitters reviewed include serotonergic agents, glutamate modulators, GABAergic medications, neuropeptides, neurosteroids, alpha- and beta-adrenergic agents, cannabinoids, and natural remedies. The outcome of the review reveals a lack of randomized double-blind placebo- controlled trials for anxiety disorders and few studies comparing novel treatments to existing anxiolytic agents. Although there are some recent randomized controlled trials for novel agents including neuropeptides, glutamatergic agents (such as ketamine and d-cycloserine), and cannabinoids (including cannabidiol) primarily in GAD or SAD, these trials have largely been negative, with only some promise for kava and PH94B (an inhaled neurosteroid). Overall, the progression of current and future psychopharmacology research in anxiety disorders suggests that there needs to be further expansion in research of these novel pathways and larger-scale studies of promising agents with positive results from smaller trials.
Highlights
Anxiety disorders are the most common class of psychiatric disorders, with a lifetime prevalence in the United States of around 32%, according to the National Comorbidity Survey Replication (NCS-R) [1]
Saffron (Crocus sativus) has been studied for depression and anxiety, due to its possible effects of inhibiting serotonin reuptake in synapses [252], there is only one listed study, a randomized, double-blind randomized controlled trial (RCT) in mild to moderate generalized anxiety disorder (GAD), its status is unknown (NCT02800733). Since this group’s last review of novel therapies for anxiety disorders in 2014 [253], there has been little headway made in the development or clinical evaluation of new drugs for panic disorder (PD), GAD, and social anxiety disorder (SAD)
There have been trials of serotonergic agents, glutamate modulators, neuropeptides, and even cannabinoids, very few have advanced to Phase III trials or have shown real promise for anxiety disorders
Summary
Anxiety disorders are the most common class of psychiatric disorders, with a lifetime prevalence in the United States of around 32%, according to the National Comorbidity Survey Replication (NCS-R) [1]. The literature, indicates that only 60–85% of patients with anxiety disorders respond (experience at least a 50% improvement) to current biological and psychological treatments [6]. There is evidence to suggest that patients with anxiety disorders, in particular generalized anxiety disorder (GAD) and SAD [7], have high rates of recurrence and/or experience persistent anxiety symptoms, especially if they have comorbid MDD [8]. Given the extensive research done separately on OCD and PTSD and their potentially divergent neurobiochemical pathways and heritability [11], this review will focus on the following DSM-5 Anxiety Disorders: PD, GAD, SAD, and SP. Ongoing clinical studies identified on the Clinical Trials database (www.clinicaltrials.gov) will be cited by their National Clinical Trial (NCT) number
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