An anxiolytic (also antipanic or antianxiety agent) is a drug that inhibits anxiety. This effect is in contrast to anxiogenic agents, which increase anxiety. Together these categories of psychoactive compounds may be referred to as anxiotropic compounds. Some recreational drugs like alcoholic beverages (which contain ethanol) induce anxiolysis. Anxiolytic medications have been used for the treatment of anxiety and its related psychological and physical symptoms. Anxiolytics have been shown to be useful in the treatment of anxiety disorders.
Anxiolytics are also known as minor tranquilizers. The term is less common in modern texts, and was originally derived from a dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.
Types of anxiolytics/anti-anxiety drugs
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, and tolerance and dependence may occur if patients stay under this treatment for longer. There is also the added problem of the accumulation of drug metabolites and adverse effects. Benzodiazepines include:
- Alprazolam (Xanax)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin, Rivotril)
- Diazepam (Valium)
- Etizolam (Etilaam) (Actually a benzodiazepine structural analog where the benzene ring has been replaced by a thiophene ring.)
- Lorazepam (Ativan)
- Oxazepam (Serax)
- Tofisopam (Emandaxin and Grandaxin) is a drug that 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.
Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (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. They can, however, be anxiogenic early on in the course of treatment due to negative feedback through the serotonergic autoreceptors. For this reason in some individuals a low dose concurrent benzodiazepine therapy might be beneficial during the early stages of serotonergic therapy to counteract the initial anxiogenic effects current serotonergics antidepressants have.
Older tricyclic antidepressants (TCAs) are anxiolytic too, however, their side effects are often more severe in nature. Examples include: imipramine, doxepin, amitriptyline, and the unrelated trazodone. Monoamine oxidase inhibitors (MAOIs) are very effective for anxiety, but due to drug dangers, are rarely prescribed. Examples include: phenelzine and tranylcypromine.
Adaptol (Mebicarum / Mebicar) is an anxiolytic produced in Lativa and used in Eastern Europe. Mebicar has an effect on the structure of limbic-reticular activity, particularly on hypothalamus emotional zone, as well as on all 4 basic neuromediator systems – γ aminobutyric acid (GASS), choline, serotonin and adrenergic activity. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, increases the brain serotonin level, and does not elicit cholinolytic action.
Afobazole is an anxiolytic drug launched in Russia in the early 2000s. It produces anxiolytic and neuroprotective effects without any sedative or muscle relaxant actions, making it more selective in action than many currently used drugs for this application. Its mechanism of action remains poorly defined however, with GABAergic, NGF and BDNF release promoting, MT1 receptor antagonism, MT3 receptor antagonism, and sigma agonism all thought to have some involvement. Clinical trials have shown afobazole to be well tolerated and reasonably effective for the treatment of anxiety, although it has yet to be introduced into widespread clinical use outside of Russia. The compound has not been evaluated by the FDA. It is unscheduled in the US and legal to import by private citizens for personal use.
Selank (Russian: Cеланк) is a nootropic, anxiolytic peptide based drug developed by the Institute of Molecular Genetics of the Russian academy of sciences. Selank is a heptapeptide with the sequence Thr-Lys-Pro-Arg-Pro-Gly-Pro. It is a synthetic analogue of a human tetrapeptide tuftsin. As such, it mimics many of its effects. It has been shown to modulate the expression of Interleukin-6 (IL-6) and affect the balance of T helper cell cytokines. It has been shown to influence the concentration of monoamine neurotransmitters and induce metabolism of serotonin. There is evidence that it may also modulate the expression of Brain-derived neurotropic factor (BDNF) in rats.
Bromantane is a stimulant drug with anxiolytic properties developed in Russia during the late 1980s, which acts mainly by inhibiting the reuptake of both dopamine and serotonin in the brain, although it also has anticholinergic effects at very high doses. Study results suggest that the combination of psychostimulant and anxiolytic actions in the spectrum of psychotropic activity of bromantane is effective in treating asthenic disorders compared to placebo. The absence of "withdrawal syndrome" demonstrated a lack of addictive potential in this drug. It is considered novel having both stimulant and anti-anxiety properties.
Tenoten is a Russian anxiolytic and antidepressant based on antibodies to brain-specific protein S-100B. S100 proteins are small calcium-binding proteins interacting with numerous intra- and extra cellular targets involved in diverse physiological functions. In particular, S100 proteins may be involved in the regulation of anxiety-related behavior
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 any more.
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. It has been shown to be less effective than benzodiazepines in the treatment of generalized anxiety disorder, while producing less side-effects.
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, in addition, 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.
Sublingual administration of Validol produces a sedative effect, and has moderate reflex and vascular dilative action caused by stimulation of sensory nerve receptors of the oral mucosa followed by the release of endorphins. Validol is typically administered as needed for symptom relief.
Certain natural substances are reputed to have anxiolytic properties, including the following:
- Bacopa monnieri (Brahmi)
- Lactuca virosa (Opium Lettuce)
- Rhodiola rosea (Arctic Weed/Golden Root)
- Hypericum perforatum (St. John's Wort)
- Matricaria recutita (German Chamomile)
- Passiflora incarnata
- Piper methysticum (Kava)
- Sceletium tortuosum (Kanna)
- Scutellaria spp. (Skullcap)
- Valeriana officinalis (Valerian)
- Salvia splendens (Not to be confused with Salvia divinorum)
- Coriandrum sativum (Coriander)
- Myristica (Nutmeg)
- Salvia elegans (Pineapple Sage)
- Inositol  In a double-blind, controlled trial, myo-inositol (18 grams daily) was superior to fluvoxamine for decreasing the number of panic attacks and had fewer side-effects.
- Cannabidiol (a cannabinoid found in marijuana)
Over-the-counter pharmaceutical drugs
Picamilon is a prodrug formed by combining niacin with GABA that is able to cross the blood–brain barrier and is then hydrolyzed into GABA and niacin. It is theorized that the GABA released in this process activates GABA receptors, with potential to produce an anxiolytic response. Picamilon is sold in the United States as a dietary supplement, while in Russia it is sold as a prescription drug.
Chlorpheniramine (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.
Melatonin has anxiolytic properties, likely mediated by the benzodiazepine/GABAergic system. It has been used experimentally as an effective premedicant for general anesthesia in surgical procedures.
Due to deficits with existing anxiolytics (either in terms of efficacy or side-effect profile), research into novel anxiolytics is active. Possible candidates for future drugs include:
Prescription-free drugs are often poor anxiolytics and often worsen the symptoms over time. However, they are often used for self-medication because of their wide availability (e.g. alcoholic beverages.)
Ethanol is used as an anxiolytic, sometimes by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain. The British National Formulary states, "Alcohol is a poor hypnotic because its diuretic action interferes with sleep during the latter part of the night." Alcohol is also known to induce alcohol related sleep disorders.
The anxiolytic effects of solvents act as positive modulators of GABAA receptors (Bowen and colleagues 2006).
Inhalants are commonly used as anxiolytics by street children in Latin America, Africa and Asia but also by impoverished indigenous communities.
Alternatives to medication
Psychotherapeutic treatment can be an effective alternative to medication. Exposure therapy is the recommended treatment for phobic anxiety disorders. Cognitive behavioral therapy (CBT) has been found to be effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Healthcare providers can also help by educating sufferers about anxiety disorders and referring individuals to self-help resources. CBT has been shown to be effective in the treatment of generalized anxiety disorder, and possibly more effective than pharmacological treatments in the long term. Sometimes medication is combined with psychotherapy but research has found that there is no benefit of combined pharmacotherapy and psychotherapy versus monotherapy.
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