Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options

Summary & key facts

This paper looked at the medicines we use now for anxiety and at new drugs being tested. The authors list many approved and off-label drugs (like antidepressants, anti-anxiety pills, blood-pressure drugs used for anxiety symptoms, and older sedatives). They then checked newer ideas, such as drugs that act on glutamate, neuropeptides, neurosteroids, and cannabinoids. Overall, the review found that there are few high-quality large trials testing new drugs for anxiety. Most recent trials of new agents have not shown clear benefit, though a couple of treatments (kava and an inhaled neurosteroid called PH94B) showed some early promise. The main takeaway is that current medicines remain the main options, and better, larger studies are needed before most new drugs can be recommended.

Key facts:

• Anxiety disorders are the most common mental health disorders and a major cause of disability worldwide.
• The review summarizes many current drug classes used for anxiety, including selective serotonin reuptake inhibitors (a type of antidepressant), serotonin–norepinephrine reuptake inhibitors (another antidepressant type), buspirone, mixed antidepressants, antipsychotics, antihistamines like hydroxyzine, blood-pressure drugs used for anxiety symptoms (for example propranolol and clonidine), and GABA-related drugs such as benzodiazepines, pregabalin, and gabapentin.
• The paper did not cover posttraumatic stress disorder or obsessive–compulsive disorder; it focused on panic disorder, generalized anxiety disorder, social anxiety disorder, and specific phobias.
• The review looked at experimental pathways being tested for anxiety, including drugs that affect serotonin, glutamate, GABA, neuropeptides, neurosteroids, the adrenaline system, cannabinoids, and some natural remedies.
• The authors found a shortage of large, high-quality randomized placebo-controlled trials testing new anxiety drugs. Few studies directly compare new drugs to existing treatments.
• Recent randomized trials of several novel agents—such as some neuropeptides, glutamate-related drugs like ketamine and d-cycloserine, and cannabinoids including cannabidiol—have mostly failed to show clear benefit, especially in generalized and social anxiety.
• Two agents showed some positive early results: kava (a plant-based remedy) and PH94B (an inhaled neurosteroid). But these findings came from small studies and need larger trials to be confirmed.
• The paper’s main conclusion is that more research and larger trials are needed before most new pharmacological treatments for anxiety can be considered proven or widely recommended.

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.

Topics

Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes Pharmacological Receptor Mechanisms and Effects Tryptophan and brain disorders

Categories

Experimental and Cognitive Psychology Psychology Social Sciences

Tags

Anxiety Anxiolytic Buspirone Generalized anxiety disorder Internal medicine Medicine Panic disorder Pregabalin Psychiatry Psychology Receptor Serotonin

Substances

Cannabis Ketamine

Conditions & symptoms

Anxiety Panic disorder and phobias Anxiety or worry Panic