Anxiety disorders are among the most common classes of psychiatric disorders, with estimates suggesting a lifetime prevalence in the US of approximately 32%. The WHO estimates there are 264 million people worldwide who have anxiety disorders.

In comparison with other psychiatric disorders, anxiety disorders may lead to a greater cost burden due to their high prevalence, and are a leading cause of disability worldwide, according to a 2020 review published in Frontiers in Psychiatry.

Garakani A, Murrough JW, Freire RC, et al. Pharmacotherapy of anxiety disorders: current and emerging treatment options. Front Psychiatry. 2020;11:595584.

 

Here, we review existing treatments for anxiety disorders and look at what's coming down the pipeline.

 

The spectrum of anxiety disorders

 

Anxiety disorders include panic disorder, generalized anxiety disorder, and the two most prevalent forms: social anxiety disorder and specific phobias. Medications used to treat these conditions— both approved and off-label use—include selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), azapirones, mixed antidepressants, antipsychotics, antihistamines, alpha and beta-adrenergic medications, and GABAergic medications.

 

A review of current treatments

 

• SSRIs and SNRIs. These are first-line therapeutic options for the treatment of panic disorder, generalized anxiety disorder, and social anxiety disorder. Both classes have been shown to be effective and well-tolerated, with minimal adverse side effects. Buspirone is the only azapirone that is FDA-approved for use in anxiety disorders. It is commonly utilized in conjunction with SSRIs or SNRIs for the treatment of generalized anxiety disorder. 

• Benzodiazepines. These drugs, which function as GABA-A agonists, are well-established as a treatment for anxiety, but they come with risks of possible tolerance and dependence. Benzodiazepines are not considered first-line monotherapy options for panic disorders or other anxiety disorders but can be used short-term in combination with SSRIs and SNRIs. 

• Antihistamines. Hydroxyzine is the only antihistamine which is FDA-approved to treat anxiety. Antihistamines are commonly utilized as alternatives to benzodiazepines for the treatment of insomnia, panic attacks, and anxiety. 

• Beta-blockers. Propranolol is a beta-adrenergic antagonist that is FDA-approved for cardiovascular-related conditions. However, it has widely been prescribed off-label for the treatment of social anxiety disorder and performance anxiety. 

 

 

How effective are existing treatments? 

There is a perception that anxiety disorders are managed properly with the existing treatment options.

 

However, studies have shown that only 60%-85% of patients suffering from anxiety disorders respond (ie, they have a minimum of 50% improvement of symptoms) to current treatments. In addition, only approximately 50% of those who respond to treatment actually achieve recovery, which is defined as having minimal anxiety symptoms—highlighting the need for new drugs to treat anxiety disorders.

 

What’s in the pipeline? 

 

There are currently some promising candidates in the developmental pipeline for treating anxiety disorders.

Sartori SB, Singewald N. Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacology & Therapeutics. 2019;204:107402.

Morris C. FDA clears LSD-based anxiety drug for clinical trials. Fortune. January 26, 2022. 

 We highlight a few of these drugs below. 

 

Gepirone-ER

Gepirone is an azapirone that is currently under a new drug application review by the FDA for the treatment of major depressive disorder. The extended-release (ER) formulation of gepirone is being used to circumvent the occurrence of adverse events that were reported with high peak plasma concentrations. So far, studies with gepirone-ER have shown that it is able to reduce clinical scores of psychic and somatic anxiety in patients who suffer from anxious depression and depression. 

Aloradine

Aloradine is currently being developed by Pherin Pharmaceuticals as a nasal spray for the treatment of social anxiety disorder. A randomized clinical trial showed that following an intranasal application, aloradine decreased social interaction and performance anxiety to a greater degree than a placebo during a public-speaking challenge among  female patients with generalized social anxiety disorder. 

SRX246

SRX246 is a small molecule, vasopressin V1A receptor antagonist that reduced reduced anxiety, fear, stress, aggression and depression in female and male patients diagnosed with intermittent explosive disorder in a phase 2 study. SRX246 is considered a promising candidate for the treatment of PTSD, generalized anxiety disorder, and anger disorders. 

MM-120

The FDA has approved a phase 2b study of an optimized form of LSD for the treatment of anxiety. The drug, called MM-120, is being developed by MindMed and is intended to treat generalized anxiety disorders and other mental conditions. MindMed is expected to begin clinical trials in 2022.