Anxiolytic

An anxiolytic (also antipanic or antianxiety agent^[1]) is a drug used for the treatment of symptoms of anxiety. Anxiolytics have been shown to be useful in the treatment of anxiety disorders.

Beta-receptor blockers such as propranolol and oxprenolol, although not anxiolytics, can be used to combat the somatic symptoms of anxiety.

Anxiolytics are also known as "minor tranquilizers",^[2] though their use and effects are by no means minor; this term is less common in modern texts.

Types of anxiolytics

Benzodiazepines

Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Benzodiazepines may also be indicated to cover the latent periods associated with the medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a first choice when short-term CNS sedation is needed. Longer-term uses include treatment for severe anxiety. There is a risk of a benzodiazepine withdrawal and rebound syndrome after continuous usage for longer than two weeks. There is also the added problem of the accumulation of drug metabolites and adverse effects.^[3] Benzodiazepines include:

• Alprazolam (Xanax)
• Chlordiazepoxide (Librium)
• Clonazepam (Klonopin)
• Diazepam (Valium)
• Lorazepam (Ativan)

Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage hypnotic properties occur.^[4]

• Tofisopam (Emandaxin and Grandaxin) is a drug which is a benzodiazepine derivative. Like other benzodiazepines, it possesses anxiolytic properties but unlike other benzodiazepines it does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties.

SSRIs

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor^[5] (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. SSRIs are primarily classified as antidepressants and typically higher dosages are required to be effective against anxiety disorders than to be effective against depression but nevertheless most SSRIs have anxiolytic properties.

Azapirones

Azapirones are a class of 5-HT_1A receptor agonists. They lack the sedation and the dependence associated with benzodiazepines and cause much less cognitive impairment. They may be less effective than benzodiazepines in patients who have been previously treated with benzodiazepines as they do not provide the sedation that these patients may expect or equate with anxiety relief. Currently approved azapirones include buspirone (Buspar) and tandospirone (Sediel). Gepirone (Ariza, Variza) is also in clinical development.

Barbiturates

Barbiturates exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable for the short-term treatment of severe insomnia, though only after benzodiazepines or non-benzodiazepines have failed. They are rarely prescribed anymore.

Hydroxyzine

Hydroxyzine (Atarax) is an old antihistamine originally approved for clinical use by the FDA in 1956. It possesses anxiolytic properties in addition to its antihistamine properties and is also licensed for the treatment of anxiety and tension. It is also used for its sedative properties as a premed before anesthesia or to induce sedation after anesthesia.^[6] It has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder while producing fewer side effects.^[7]

Pregabalin

Pregabalin's therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam and venlafaxine but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance and additionally unlike benzodiazepines it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.^[8][9]

Herbal treatments

Certain herbs are reputed to have anxiolytic properties, including the following:

• Rhodiola rosea (Arctic Weed/Golden Root)
• Bacopa monnieri (Brahmi)
• Hypericum perforatum (St. John's Wort)
• Matricaria recutita (German Chamomile)
• Mitragyna speciosa (Kratom)
• Cannabis sativa (Cannabis)
• Nepeta persica (Catnip)
• Piper methysticum (Kava)
• Sceletium tortuosum (Kanna)
• Scutellaria spp. (Skullcap)
• Valeriana officinalis (Valerian)

Of these, only Kava and Brahmi have shown anxiolytic effects in randomized clinical trials, and only Kava's effect has been independently replicated.^[10]

In mice, trials have shown anxiolytic effects at 50 mg kg−1. However an increase in the dose of N. persica exerted stimulation rather than sedation as is the case for many other herbs.^[11]

A team from Brazil found cannabidiol (a constituent of cannabis; also called CBD) to be an effective anti-psychotic and anxiolytic ^[12]. "CBD induced a clear anxiolytic effect and a pattern of cerebral activity compatible with anxiolytic activity. Therefore, similar to the data obtained in animal models, results from studies on healthy volunteers have strongly suggested an anxiolytic-like effect of CBD."

Pineapple sage, or salvia elegans, is used as a treatment for anxiety in traditional Mexican medicine, and a preliminary study on mice has yielded some support for both anxiolytic and antidepressant properties.^[13]

Over-the-counter

Chlorpheniramine^[14] (Chlor-Trimeton) and diphenhydramine (Benadryl) have hypnotic and sedative effects with mild anxiolytic-like properties(off-label use). These drugs are approved by the FDA for allergies, rhinitis, and urticaria.

Future drugs

Due to deficits with existing anxiolytics (either in terms of efficacy or side-effect profile), research into novel anxioltyics is active. Possible candiates for future drugs include:

• BNC210

Alternatives to medication

Psychotherapy (e.g., cognitive behavioral therapy (CBT)) is often useful as an adjunct to medication or as an alternative to medication. Research has demonstrated better long-term results for general anxiety when treated with psychotherapy as opposed to pharmacotherapy alone.

Meditation is also known for its tendency to reduce anxiety.

See also

• ATC code N05#N05B Anxiolytics

References