Anxiolytic

An anxiolytic (/ˌæŋksiəˈlɪtɪk, ˌæŋksioʊ-/; also antipanic or antianxiety agent)[1] is a medication, or other intervention, that reduces anxiety. This effect is in contrast to anxiogenic agents, which increase anxiety. Together these categories of psychoactive compounds or interventions may be referred to as anxiotropic compounds or agents. Some recreational drugs such as alcohol induce anxiolysis initially; however, studies show that many of these drugs are anxiogenic. Anxiolytic medications have been used for the treatment of anxiety disorder and its related psychological and physical symptoms. Light therapy and other interventions have also been found to have an anxiolytic effect.[2]

Anxiolytic
Drug class
Class identifiers
Synonymssedative, minor tranquilizer
UseAnxiety disorders
Clinical data
Drugs.comDrug Classes
In Wikidata

Beta-receptor blockers such as propranolol and oxprenolol, although not anxiolytics, can be used to combat the somatic symptoms of anxiety such as tachycardia and palpitations.[3]

Anxiolytics are also known as minor tranquilizers.[4] The term is less common in modern texts and was originally derived from a dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.[5]

There are concerns that some GABAergics, such as benzodiazepines and barbiturates, may have an anxiogenic effect if used over long periods of time.[6]

Medications

Barbiturates
Main article: Barbiturate

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.[7]

Benzodiazepines
Main article: Benzodiazepine

Benzodiazepines are prescribed for short-term and long-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. If benzodiazepines are discontinued rapidly after being taken daily for two or more weeks there is some risk of benzodiazepine withdrawal and rebound syndrome, which varies by the specific drug.[8] Tolerance and dependence may also occur, but may be clinically acceptable,[9] also the risk of abuse is significantly smaller than in case of barbiturates. Cognitive and behavioral adverse effects are possible.[10] Benzodiazepines include:

Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage hypnotic properties occur.[11]

Carbamates

Marketed as a safer alternative to barbiturate anxiolytics, meprobamate (Miltown, Equanil) was commonly used to relieve anxiety in the late 1950s and 1960s. Like barbiturates, therapeutic doses produce sedation and significant overdoses may be fatal. In the US, meprobamate has generally been replaced with benzodiazepines while the drug is now withdrawn in many European countries and Canada. The muscle relaxant carisoprodol has anxiolytic effects by metabolizing to meprobamate. Various other carbamates have been found to share these effects, such as tybamate and lorbamate.

Antihistamines
Main article: Antihistamines

Hydroxyzine (Atarax) is an antihistamine originally approved for clinical use by the FDA in 1956. In addition to its antihistamine properties hydroxyzine possesses anxiolytic properties and is approved for the treatment of anxiety and tension. Its sedative properties are useful as a premedication before anesthesia or to induce sedation after anesthesia.[12] Hydroxyzine has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.[13]

Chlorpheniramine (Chlor-Trimeton)[14] 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.

Opioids

Opioids are drugs that are usually only prescribed for their painkilling properties, but some research is beginning to find that some varieties are effective at treating depression, obsessive compulsive disorder, and other ailments often associated with or caused by anxiety. They have a very high potential for abuse and have one of the highest addiction rates for all drugs. Many people become addicted to these drugs because they are so effective at blocking emotional pain, including anxiety. Similarly to alcohol, people with anxiety disorders are more likely to become addicted to opioids due to their anxiolytic effect. These drugs range from the commonly prescribed hydrocodone, to the often illegal heroin, and all the way to much more potent varieties like fentanyl often used in trauma or end of life pain management. Most people purchasing these drugs illegally are seeking them out to get a euphoric like high, but many others seek them out because they are so effective at reducing both physical pain and emotional pain.[15]

It appears that buprenorphine is gaining some acceptability within the medical community for treating anxiety, OCD, and depression. Buprenorphine is similar to methadone in that it is used in opioid replacement therapy as well as pain management. It is safer than methadone and other opioids and has a very long half-life leading to less compulsive use among those who attempt to abuse it or have become dependent on it. There has been research into more commonly abused opioids being prescribed for anxiety disorder, but given that these drugs produce more euphoria and require more constant dosing when compared to buprenorphine, there is a much higher danger for abuse and overdose.[16]

Antidepressants

Antidepressant medications can reduce anxiety, and several selective serotonin reuptake inhibitors have been USFDA approved to treat various anxiety disorders. Antidepressants are especially beneficial because anxiety and depression often occur together.[8]

Selective serotonin reuptake inhibitors

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitors[17] (SSRIs) are a class of compounds typically used in the treatment of depression, anxiety disorders, OCD and some personality disorders. Primarily classified as antidepressants, most SSRIs have anxiolytic effects.[18] Some are FDA approved for certain anxiety related disorder and/or OCD related disorders (possibly reflecting their unique strengths;) however they are routinely used off label interchangeably, often beginning with a trial and error process, as they are a relatively safe and preferred class of psychiatric medication compared to the typical alternatives.

Some have been described as particularly helpful for specific types of anxiety, OCD, etc. Dosages vary when compared the typical antidepressant dose. Those for OCD are often the maximum typical antidepressant doses or higher, while panic disorder is often treated with the lowest antidepressant dose.

Paradoxically, SSRIs can increase anxiety initially due to negative feedback through the serotonergic autoreceptors. For this reason a concurrent benzodiazepine is sometimes used temporarily 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.[19]

Tricyclic antidepressants

Tricyclic antidepressants (TCAs) have anxiolytic effects; however, side effects are often more troubling or severe and overdose is dangerous. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.[20]

Tetracyclic antidepressant

Mirtazapine has demonstrated anxiolytic effects with a better side effect profile to all other classes of antidepressants, yet this is disputed by evidence that withdrawal is comparatively more severe than SSRI's, it is far more dangerous in overdose, it has a higher risk of causing life-threatening agrangulocytosis, it has more potential for adverse drug-drug interactions, and some find it noticeably sedating.

It rarely causes or exacerbates anxiety, is sometimes particularly advantageous in certain individuals, with certain variants of depression, anxiety, or both, and its effectiveness tends to occur significantly faster than SSRIs.

In many countries (such as USA and Australia), it is not specifically approved for anxiety disorders, being selected as an antidepressant when anxiety is co-occurring, or used off label. Use of mirtazapine for anxiety disorders in the absence of depressive symptoms is uncommon.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are effective for anxiety, but their dietary restrictions, side effects and availability of newer effective drugs, have limited their use.[8] First generation MAO inhibitors include: phenelzine, isocarboxazid and tranylcypromine. Moclobemide, a reversible MAO-A inhibitor, lacks the dietary restrictions associated with classic MAOI's. The drug is used in Canada, the UK and Australia.

Sympatholytics

Sympatholytics are a group of anti-hypertensives which inhibit activity of the sympathetic nervous system, and several medications within this group have shown anxiolytic effects as well as potential therapy for PTSD.

Beta blockers

Although not officially approved for this purpose, beta blockers also can have an antianxiety effect.[21][22]

Alpha blockers

The alpha1 antagonist prazosin could be effective for PTSD[23][24]

Alpha-adrenergic agonist

The Alpha-2 adrenergic receptor agonists clonidine[25] and guanfacine have demonstrated both anxiolytic and anxiogenic effects.

Phenibut

Phenibut (brand names Anvifen, Fenibut, Noofen) is an anxiolytic[26] used in Russia.[27] Phenibut is a GABAB receptor agonist,[26] as well as an antagonist at α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin.[28] The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.[29]

Mebicar

Mebicar (mebicarum) is an anxiolytic produced in Latvia 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 (GABA), choline, serotonin and adrenergic activity.[30] Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, and increases the brain serotonin level.[31]

Fabomotizole

Fabomotizole[32] (brand name Afobazole) is an anxiolytic drug launched in Russia in the early 2000s. Its mechanism of action remains poorly defined, with GABAergic, NGF and BDNF release promoting, MT1 receptor agonism, MT3 receptor antagonism, and sigma agonism all thought to have some involvement.[33][34][35][36][37] It has yet to find clinical use outside of Russia.

Selank

Selank is an 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 analog 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. There is evidence that it may also modulate the expression of brain-derived neurotropic factor in rats.

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), a.k.a. DOPA decarboxylase),[38][39] although at very high doses bromantane also has anticholinergic effects. 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.

Emoxypine

Emoxypine is an antioxidant that is also a purported anxiolytic.[40][41] Its chemical structure resembles that of pyridoxine, a form of vitamin B6.

Azapirones

Azapirones are a class of 5-HT1A receptor agonists. Currently approved azapirones include buspirone (Buspar) and tandospirone (Sediel).[42]

Pregabalin

Pregabalin's anxiolytic effect appears after one week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but has demonstrated more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance, and unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment. Pregabalin also exhibits a lower potential for abuse and dependence than benzodiazepines.[43][44]

Menthyl isovalerate

Menthyl isovalerate is a flavoring food additive which is marketed as a sedative and anxiolytic drug in Russia under the name Validol.[45][46]

Propofol

Propofol produces anxiolytic effect, beneficial during medical procedures requiring sedation.[47][48]

Racetams

Some racetam based drugs such as aniracetam can have an antianxiety effect.[49]

Alcohol
See also: Short-term effects of alcohol consumption

Ethanol is used as an anxiolytic, sometimes by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.[50] 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.[51]

Alternatives to medication

Psychotherapeutic treatment can be an effective alternative to medication.[52] 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.[53] 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.[54] Sometimes medication is combined with psychotherapy, but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.[55]

However, even with CBT being a viable treatment option, it can still be ineffective for many individuals. Both the Canadian and American medical associations then suggest the use of a strong but long lasting benzodiazepine such as clonazepam and an antidepressant, usually Prozac for its effectiveness.[56]

See also

Categories
► <a href='/wiki/Category:Anxiolytics' title='Category:Anxiolytics'>Anxiolytics</a>
► <a href='/wiki/Category:Drug_classes_defined_by_psychological_effects' title='Category:Drug classes defined by psychological effects'>Drug classes defined by psychological effects</a>
► <a href='/wiki/Category:Drugs_by_psychological_effects' title='Category:Drugs by psychological effects'>Drugs by psychological effects</a>
► <a href='/wiki/Category:Psychoactive_drugs' title='Category:Psychoactive drugs'>Psychoactive drugs</a>

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