Introduction

An anxiolytic (also anti-panic or anti-anxiety agent) is a medication or other intervention that reduces anxiety.

This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxiety disorder and its related psychological and physical symptoms.

Medications

Barbiturates

Barbiturates are powerful anxiolytics but 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.

Benzodiazepines

Benzodiazepines are prescribed to quell panic attacks. Benzodiazepines are also prescribed in tandem with an antidepressant for the latent period of efficacy associated with many ADs for anxiety disorder. There is risk of benzodiazepine withdrawal and rebound syndrome if BZDs are rapidly discontinued. Tolerance and dependence may occur. The risk of abuse in this class of medication is smaller than in that of barbiturates. Cognitive and behavioural adverse effects are possible.

Benzodiazepines include: Alprazolam (Xanax), Bromazepam, Chlordiazepoxide (Librium), Clonazepam (Klonopin), Diazepam (Valium), Lorazepam (Ativan), Oxazepam, Temazepam, and Triazolam.

Antidepressants

Antidepressant medications can reduce anxiety. The SSRIs paroxetine and lexapro and SNRIs venlafaxine and duloxetine are US Food and Drug Administration (FDA) approved to treat generalised anxiety disorder.

Selective Serotonin Reuptake Inhibitors

Selective serotonin reuptake inhibitors (SSRIs) are a class of medications used in the treatment of depression, anxiety disorders, OCD and some personality disorders. SSRIs can increase anxiety initially due to negative feedback through the serotonergic autoreceptors, for this reason a concurrent benzodiazepine can be used until the anxiolytic effect of the SSRI occurs.

Serotonin-Norepinephrine Reuptake Inhibitors

Serotonin-norepinephrine reuptake inhibitor (SNRIs) include venlafaxine and duloxetine drugs. Venlafaxine, in extended release form, and duloxetine, are indicated for the treatment of GAD. SNRIs are as effective as SSRIs in the treatment of anxiety disorders.

Tricyclic Antidepressants

Tricyclic antidepressants (TCAs) have anxiolytic effects; however, side effects are often more troubling or severe and overdose is dangerous. They’re effective, but they’ve generally been replaced by antidepressants that cause fewer adverse effects. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.

Tetracyclic Antidepressant

Tetracyclic antidepressants, such as Mirtazapine, have demonstrated anxiolytic effect comparable to SSRIs while rarely causing or exacerbating anxiety. Mirtazapine’s anxiety reduction tends to occur significantly faster than SSRIs.

Monoamine Oxidase Inhibitors

Monoamine oxidase inhibitors (MAOIs) are first generation antidepressants effective for anxiety treatment but their dietary restrictions, adverse effect profile and availability of newer medications have limited their use. MAOIs include phenelzine, isocarboxazid and tranylcypromine. Pyrazidol is a reversible MAOI that lacks dietary restriction.

Sympatholytics

Sympatholytics are a group of anti-hypertensives which inhibit activity of the sympathetic nervous system. Beta blockers reduce anxiety by decreasing heart rate and preventing shaking. Beta blockers include propranolol, oxprenolol, and metoprolol. The Alpha-1 agonist prazosin could be effective for PTSD. The Alpha-2 agonists clonidine and guanfacine have demonstrated both anxiolytic and anxiogenic effects.

Miscellaneous

Buspirone

Buspirone (Buspar) is a 5-HT1A receptor agonist used to treated generalised anxiety disorder. If an individual has taken a benzodiazepine, buspirone will be less effective.

Pregabalin

Pregabalin (Lyrica) produces anxiolytic effect after one week of use comparable to lorazepam, alprazolam, and venlafaxine with more consistent psychic and somatic anxiety reduction. Unlike BZDs, it does not disrupt sleep architecture nor does it cause cognitive or psychomotor impairment.

Hydroxyzine

Hydroxyzine (Atarax) is an antihistamine originally approved for clinical use by the FDA in 1956. Hydroxyzine has a calming effect which helps ameliorate anxiety. Hydroxyzine efficacy is comparable to benzodiazepines in the treatment of generalised anxiety disorder. Hydroxyzine is typically only used for short term anxiety relief.

Phenibut

Phenibut (Anvifen, Fenibut, Noofen) is an anxiolytic used in Russia. Phenibut is a GABA_B receptor agonist, as well as an antagonist at α₂δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin. The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.

Mebicar

Mebicar is an anxiolytic produced in Latvia and used in Eastern Europe. Mebicar has an effect on the structure of limbic-reticular activity, particularly on the hypothalamus, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity. Mebicar decreases noradrenaline, increases serotonin, and exerts no effect on dopamine.

Fabomotizole

Fabomotizole (Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. Its mechanism of action is poorly defined, with GABAergic, NGF and BDNF release promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism thought to have some involvement.

Bromantane

Bromantane is a stimulant drug with anxiolytic properties developed in Russia during the late 1980s. Bromantane acts mainly by facilitating the biosynthesis of dopamine, through indirect genomic upregulation of relevant enzymes (tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD).

Emoxypine

Emoxypine is an antioxidant that is also a purported anxiolytic. Its chemical structure resembles that of pyridoxine, a form of vitamin B₆.

Menthyl Isovalerate

Menthyl isovalerate is a flavouring food additive marketed as a sedative and anxiolytic drug in Russia under the name Validol.

Racetams

Some racetam based drugs such as aniracetam can have an antianxiety effect.

Etifoxine

Having similar anxiolytic effects as benzodiazepine drugs, etifoxine does not produce the same levels of sedation and ataxia. Further, etifoxine does not affect memory and vigilance, and does not induce rebound anxiety, drug dependence, or withdrawal symptoms.

Alcohol

Ethanol is sometimes used as an anxiolytic by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.

Alternatives to Medication

Cognitive behavioural therapy (CBT) is an effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder, while exposure therapy is the recommended treatment for anxiety related phobias. Healthcare providers can guide those with anxiety disorder by referring them to self-help resources. Sometimes medication is combined with psychotherapy but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.

If CBT is found ineffective, both the Canadian and American medical associations then suggest the use of a potent, long lasting benzodiazepine such as clonazepam and an antidepressant, usually Prozac for its effectiveness.