Anxiolytic

Anxiety is a naturally-occurring emotion and response. When anxiety levels exceed the tolerability of a person, anxiety disorders may occur. People with anxiety disorders can exhibit fear responses, such as defensive behaviors, high levels of alertness, and negative emotions. Those with anxiety disorders may have concurrent psychological disorders, such as depression. Anxiety disorders are classified using six possible clinical assessments:{{Cite book |editor-last=Whittlesea |editor-first=Cate|editor-last2= Hodson|editor-first2= Karen |url=http://worldcat.org/oclc/1084882482 |title=Clinical pharmacy and therapeutics |date=7 August 2018 |publisher=Elsevier |isbn=978-0-7020-7012-9 |oclc=1084882482}}

Different types of anxiety disorders will share some general symptoms while having their own distinctive symptoms. This explains why people with different types of anxiety disorders will respond differently to different classes of anti-anxiety medications.

The etiology of anxiety disorder remains unknown. There are several contributing factors that are still yet to be proved to cause anxiety disorders. These factors include childhood anxiety, drug induction by central stimulant drugs, metabolic diseases or having depressive disorder.

Anti-anxiety medication is any drug that can be taken or prescribed for the treatment of anxiety disorders, which may be mediated by neurotransmitters like norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (GABA) in the central nervous system.{{Cite web |title=Anxiolytics and you: How anxiety medications can help. |url=https://my.clevelandclinic.org/health/treatments/24776-anxiolytics |access-date=2024-01-15 |website=Cleveland Clinic |language=en}} Anti-anxiety medication can be classified into six types according to their different mechanisms: antidepressants, benzodiazepines, azapirones, antiepileptics, antipsychotics, and beta blockers.{{Cite web |title=Anxiety: Pharmacotherapy |url=https://www.camh.ca/en/professionals/treating-conditions-and-disorders/anxiety-disorders/anxiety---treatment/anxiety---pharmacotherapy |access-date=2024-01-15 |website=CAMH |language=en-CA}}

Antidepressants include selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase inhibitors (MAOIs). SSRIs are used in all types of anxiety disorders while SNRIs are used for generalized anxiety disorder (GAD). Both of them are considered as first-line anti-anxiety medications. TCAs are second-line treatment as they cause more significant adverse effects when compared to the first-line treatment. Benzodiazepines are effective in emergent and short-term treatment of anxiety disorders due to their fast onset but carry the risk of dependence. Buspirone is indicated for GAD, which has much slower onset but with the advantage of less sedating and withdrawal effects.{{Cite journal |last1=Cassano |first1=Giovanni B. |last2=Rossi |first2=Nicolò Baldini |last3=Pini |first3=Stefano |date=2002 |title=Psychopharmacology of anxiety disorders |journal=Dialogues in Clinical Neuroscience |volume=4 |issue=3 |pages=271–285 |doi=10.31887/DCNS.2002.4.3/gcassano |issn=1294-8322 |pmc=3181684 |pmid=22033867}}

The first monoamine oxidase inhibitor (MAOI), iproniazid, was discovered accidentally when developing the new antitubercular drug isoniazid. The drug was found to induce euphoria and improve the patient's appetite and sleep quality.{{Cite journal |last1=Van Der Walt |first1=Martie |last2=Keddy |first2=Karen H. |date=2021-06-01 |title=The Tuberculosis-Depression Syndemic and Evolution of Pharmaceutical Therapeutics: From Ancient Times to the Future |journal=Frontiers in Psychiatry |volume=12 |pages=617751 |doi=10.3389/fpsyt.2021.617751 |doi-access=free |issn=1664-0640 |pmc=8203803 |pmid=34140898}}

The first tricyclic antidepressant, imipramine, was originally developed and studied to be an antihistamine alongside other first-generation antihistamines of the time, such as promethazine.{{Cite journal |last1=Hillhouse |first1=Todd M. |last2=Porter |first2=Joseph H. |title=A brief history of the development of antidepressant drugs: From monoamines to glutamate. |url=http://dx.doi.org/10.1037/a0038550 |journal=Experimental and Clinical Psychopharmacology |year=2015 |volume=23 |issue=1 |pages=1–21 |doi=10.1037/a0038550 |pmid=25643025 |pmc=4428540 |issn=1936-2293}} TCAs can increase the level of norepinephrine and serotonin by inhibiting their reuptake transport proteins.{{Citation |last1=Moraczewski |first1=Jordan |title=Tricyclic Antidepressants |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK557791/ |work=StatPearls |access-date=2024-01-15 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491723 |last2=Awosika |first2=Ayoola O. |last3=Aedma |first3=Kapil K.}} The majority of TCAs exert greater effect on norepinephrine, which leads to side effects like drowsiness and memory loss. {{citation needed|date=January 2024}}

In order to be more effective on serotonin agonism and avoid anticholinergic and antihistaminergic side effects, selective serotonin reuptake inhibitors (SSRI) were researched and introduced to treat anxiety disorders. The first SSRI, fluoxetine (Prozac), was discovered in 1974 and approved by FDA in 1987. After that, other SSRIs like sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro) have entered the market.

The first serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine (Effexor), entered the market in 1993. SNRIs can target serotonin and norepinephrine transporters while avoiding imposing significant effects on other adrenergic (α₁, α₂, and β), histamine (H₁), muscarinic, dopamine, or postsynaptic serotonin receptors.{{Citation |last=Chu |first=Andrew |title=Selective Serotonin Reuptake Inhibitors |date=2025 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK554406/ |access-date=2025-04-22 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32119293 |last2=Wadhwa |first2=Roopma}}

There are six groups of anti-anxiety medications available that have been proven to be clinically significant in treatment of anxiety disorders.{{Citation |title=Rang and Dale's Pharmacology 7th Edition Preface |date=2012 |url=http://dx.doi.org/10.1016/b978-0-7020-3471-8.00064-0 |work=Rang & Dale's Pharmacology |pages=xv |publisher=Elsevier |doi=10.1016/b978-0-7020-3471-8.00064-0 |isbn=9780702034718 |access-date=2022-03-16|url-access=subscription }} The groups of medications are as follows.

Medications that are indicated for both anxiety disorders and depression. Selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are new generations of antidepressants. They have a much lower adverse effect profile than older antidepressants like monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). Therefore, SSRIs and SNRIs are now the first-line agent in treating long term anxiety disorders, given their applications and significance in all six types of disorders.

Benzodiazepines are used for acute anxiety and could be added along with current use of SSRIs to stabilize a treatment. Long-term use in treatment plans is not recommended. Different kinds of benzodiazepine will vary in its pharmacological profile, including its strength of effect and time taken for metabolism. The choice of the benzodiazepine will depend on the corresponding profiles.

Benzodiazepines are used for emergent or short-term management. They are not recommended as the first-line anti-anxiety drugs, but they can be used in combination with SSRIs/SNRIs during the initial treatment stage. Indications include panic disorder, sleep disorders, seizures, acute behavioral disturbance, muscle spasm and premedication and sedation for procedures.{{Cite web |title=Benzodiazepines: What They Are, Uses, Side Effects & Risks |url=https://my.clevelandclinic.org/health/treatments/24570-benzodiazepines-benzos |access-date=2024-01-15 |website=Cleveland Clinic |language=en}}

Buspirone can be useful in GAD but not particularly effective in treating phobias, panic disorder or social anxiety disorders. It is a safer option for long-term use as it does not cause dependence like benzodiazepines.{{Cite web |date=2022-11-23 |title=BuSpar For Anxiety: Is It Right For Me? {{!}} Klarity |url=https://www.klarityadhd.com/post/buspar-for-anxiety-is-it-right-for-me/ |access-date=2023-10-19 |website=www.klarityadhd.com |language=en-US}}

Antiepileptics are rarely prescribed as an off-label treatment for anxiety disorders and post-traumatic stress disorders.{{Cite web |date=2014-10-28 |title=What is the Best Anticonvulsant for Anxiety? |url=https://psychcentral.com/anxiety/antipsychotics-anticonvulsants-for-anxiety-disorders |access-date=2023-10-19 |website=Psych Central |language=en}} There have been some suggestions that they may help with anxiety symptoms but there is generally a lack of research on its use.{{Cite journal |last1=Garakani |first1=Amir |last2=Murrough |first2=James W. |last3=Freire |first3=Rafael C. |last4=Thom |first4=Robyn P. |last5=Larkin |first5=Kaitlyn |last6=Buono |first6=Frank D. |last7=Iosifescu |first7=Dan V. |date=2020 |title=Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options |journal=Frontiers in Psychiatry |volume=11 |doi= 10.3389/fpsyt.2020.595584|doi-access=free |pmid=33424664 |pmc=7786299 |issn=1664-0640}}

One antiepileptic, pregabalin, has been found to be better at treating GAD than a placebo, and comparable effects to benzodiazepines. It has also been shown be potentially efficient in treating social anxiety disorder. Gabapentin has been prescribed off-label for anxiety despite a lack of research evidence supporting such use, although some studies have indicated that it may relieve anxiety symptoms. The potential anxiolytic effect of tiagabine has been observed in some pre-clinical trials, but its effectiveness has not yet been proved. Similarly, there is a lack of research on valproate for the treatment of anxiety disorders.

Olanzapine and risperidone are atypical antipsychotics which are also effective in GAD and PTSD treatment. However, there is a higher chance of experiencing adverse effects than the other anti-anxiety medications.

Propranolol is originally used for high blood pressure and heart diseases. It can also be used to treat anxiety with symptoms like tremor or increased heart rate. They work on the nervous system and alleviate the symptoms as a relief. Propranolol is also commonly used for public speaking when one is nervous.

Both selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) are reuptake inhibitors of a class of nerve signal transduction chemical called neurotransmitters. Serotonin and norepinephrine are neurotransmitters that are related to nervous control in mood regulation. The level of these neurotransmitters is regulated by the nerve through reuptake to avoid accumulation of the neurotransmitter at the endings of nerve fibers. By reuptaking the neurotransmitter, the level of neuronal activity will go back down and be ready to go back up upon excitation from a new nerve signal. However the neurotransmitter level of patients with anxiety disorders is usually low or the patients’ nerve fibers are insensitive to the neurotransmitters. SSRIs and SNRIs will then block the channel of reuptake and increase the level of the neurotransmitter. The nerve fibers will inhibit further production of neurotransmitters upon the increase. However the prolonged increase will eventually desensitize the nerve about the change in level. Therefore, the action of both SSRIs and SNRIs will take 4–6 weeks to exert their full effect.

Benzodiazepines bind selectively to the GABA receptor, which is the receptor protein found in the nervous system and is in control of the nervous response. Benzodiazepine will increase the entry of chloride ions into the cells by improving the binding between GABA and GABA receptors and then the better opening of the channel for chloride ion passage. The high level of chloride ion inside the nerve cells makes the nerve more difficult to depolarize and inhibit further nerve signal transduction. The excitability of the nerves then reduces and the nervous system slows down. Therefore, the drug can alleviate symptoms of anxiety disorder and make the person less nervous.

Selective serotonin reuptake inhibitors (SSRIs) are a class of medications used in the treatment of depression, anxiety disorders, OCD and some personality disorders.{{cite journal |last1=Kanba |first1=S. |year=2004 |title=Although antidepressants and anxiolytics are frequently used together to treat depression in the acute phase, how effective is the concomitant use of these drugs? |journal=Journal of Psychiatry & Neuroscience |volume=29 |issue=6 |pages=485 |pmc=524966 |pmid=15644990}}{{cite book |author=Barlow, David H. |title=Abnormal Psychology: An Integrative Approach |author2=Durand, Mark V |publisher=Wadsworth Cengage Learning |year=2009 |isbn=978-0-495-09556-9 |edition=Fifth |location=Belmont, CA |page=239 |chapter=Chapter 7: Mood Disorders and Suicide |oclc=192055408}}{{page needed|date=August 2016}} SSRIs are the first-line anti-anxiety medications.{{Citation |last1=Lochmann |first1=Dee |title=Selective Serotonin Reuptake Inhibitors |date=2018 |url=http://link.springer.com/10.1007/164_2018_172 |work=Antidepressants |volume=250 |pages=135–144 |editor-last=Macaluso |editor-first=Matthew |place=Cham |publisher=Springer International Publishing |language=en |doi=10.1007/164_2018_172 |isbn=978-3-030-10948-6 |access-date=2022-03-16 |last2=Richardson |first2=Tara |pmid=30838457 |editor2-last=Preskorn |editor2-first=Sheldon H.|url-access=subscription }} Serotonin is one of the crucial neurotransmitters in mood enhancement, and increasing serotonin level produces an anti-anxiety effect.{{Cite web |title=Serotonin: What Is It, Function & Levels |url=https://my.clevelandclinic.org/health/articles/22572-serotonin |access-date=2024-01-15 |website=Cleveland Clinic |language=en}} SSRIs increase the serotonin level in the brain by inhibiting serotonin uptake pumps on serotonergic systems, without interactions with other receptors and ion channels. SSRIs are beneficial in both acute response and long-term maintenance treatment for both depression and anxiety disorder.

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.{{Cite journal |last1=Dunlop |first1=Boadie W. |last2=Davis |first2=Paula G. |date=2008 |title=Combination Treatment With Benzodiazepines and SSRIs for Comorbid Anxiety and Depression: A Review |journal=Primary Care Companion to the Journal of Clinical Psychiatry |volume=10 |issue=3 |pages=222–228 |doi=10.4088/pcc.v10n0307 |issn=1523-5998 |pmc=2446479 |pmid=18615162}}

The SSRIs paroxetine and escitalopram are USFDA approved to treat generalized anxiety disorder.

The common early side effects of SSRIs include nausea and loose stool, which can be solved by discontinuing the treatment. Headache, dizziness, insomnia are the common early side effects as well.{{Cite web |date=2021-02-15 |title=Side effects - Selective serotonin reuptake inhibitors (SSRIs) |url=https://www.nhs.uk/mental-health/talking-therapies-medicine-treatments/medicines-and-psychiatry/ssri-antidepressants/side-effects/ |access-date=2024-01-15 |website=nhs.uk |language=en}}

Sexual dysfunction, anorgasmia, erectile dysfunction, and reduced libido are common adverse side effects of SSRIs. Sometimes they may persist after the cessation of treatment.

Withdrawal symptoms like dizziness, headache and flu-like symptoms (fatigue/myalgia/loose stool) may occur if SSRI is stopped suddenly. The brain is incapable of upregulating the receptors to sufficient levels especially after discontinuation of the drugs with short half life like paroxetine. Both fluoxetine and its active metabolite have a long half life therefore it causes the least withdrawal symptoms.{{Cite journal |date=June 2017 |title=Treatment of anxiety disorders |url=http://dx.doi.org/10.31887/dcns.2017.19.2/bbandelow |journal=Generalized Anxiety Disorders |volume=19 |issue=2 |pages=93–107 |doi=10.31887/dcns.2017.19.2/bbandelow |issn=2608-3477|last1=Bandelow |first1=Borwin |last2=Michaelis |first2=Sophie |last3=Wedekind |first3=Dirk |pmid=28867934 |pmc=5573566 }}

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.{{cite book |author1=John Vanin |title=Anxiety Disorders: A Pocket Guide For Primary Care |author2=James Helsley |date=19 June 2008 |publisher=Springer Science & Business Media |page=189}}

Tricyclic antidepressants (TCAs) have anxiolytic effects; however, side effects are often more troubling or severe and overdose is dangerous. They are considered effective, but have generally been replaced by antidepressants that cause different adverse effects. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.{{cite book|last1=Post|first1=Jason W.|last2=Migne|first2=Louis J.|title=Antidepressants : Pharmacology, Health Effects and Controversy|date=2012|publisher=Nova Science Publishers|location=New York|isbn=9781620815557|page=58}}{{Cite web|url=https://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046983|title = Tricyclic antidepressants (TCAs)|website = Mayo Clinic}}

TCAs may cause drug poisoning in patients with hypotension, cardiovascular diseases and arrhythmias.{{Cite journal |last1=Thanacoody |first1=H. K. Ruben |last2=Thomas |first2=Simon H. L. |date=2005 |title=Tricyclic antidepressant poisoning : cardiovascular toxicity |url=https://pubmed.ncbi.nlm.nih.gov/16390222/#:~:text=Tricyclic%20antidepressants%20remain%20a%20common,be%20particularly%20toxic%20in%20overdose. |journal=Toxicological Reviews |volume=24 |issue=3 |pages=205–214 |doi=10.2165/00139709-200524030-00013 |issn=1176-2551 |pmid=16390222|s2cid=44532041 }}

Mirtazapine has demonstrated anxiolytic effect comparable to SSRIs while rarely causing or exacerbating anxiety. Mirtazapine's anxiety reduction tends to occur significantly faster than SSRIs.{{Cite journal |last1=Montano |first1=C. Brendan |last2=Jackson |first2=W. Clay |last3=Vanacore |first3=Denise |last4=Weisler |first4=Richard |date=2023-07-04 |title=Considerations when selecting an antidepressant: a narrative review for primary care providers treating adults with depression |journal=Postgraduate Medicine |language=en |volume=135 |issue=5 |pages=449–465 |doi=10.1080/00325481.2023.2189868 |pmid=36912037 |issn=0032-5481|doi-access=free }}

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. Pirlindole is a reversible MAOI that lacks dietary restriction.{{Cite journal |last1=Tanghe |first1=A. |last2=Geerts |first2=S. |last3=Van Dorpe |first3=J. |last4=Brichard |first4=B. |last5=Bruhwyler |first5=J. |last6=Géczy |first6=J. |date=August 1997 |title=Double-blind randomized controlled study of the efficacy and tolerability of two reversible monoamine oxidase A inhibitors, pirlindole and moclobemide, in the treatment of depression |url=https://pubmed.ncbi.nlm.nih.gov/9272198/ |journal=Acta Psychiatrica Scandinavica |volume=96 |issue=2 |pages=134–141 |doi=10.1111/j.1600-0447.1997.tb09918.x |issn=0001-690X |pmid=9272198 |s2cid=23485112}}

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.{{Cite book|title=Lehne's pharmacology for nursing care|last1=Burchum|first1=Jacqueline Rosenjack|last2=Rosenthal |first2=Laura D. |isbn=9780323321907|edition=9th|location=St. Louis, Missouri|oclc=890310283|date = 2015-01-29}}

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.{{Cite journal|last1=Cassano|first1=Giovanni B.|last2=Rossi|first2=Nicolò Baldini|last3=Pini|first3=Stefano|date=2002|title=Psychopharmacology of anxiety disorders|journal=Dialogues in Clinical Neuroscience|volume=4|issue=3|pages=271–285|doi=10.31887/DCNS.2002.4.3/gcassano|issn=1294-8322|pmc=3181684|pmid=22033867}} Tolerance and dependence may occur.Gelder, M, Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp236. The risk of abuse in this class of medication is smaller than in that of barbiturates. Cognitive and behavioral adverse effects are possible.{{cite journal |vauthors=Lader M, Tylee A, Donoghue J |title=Withdrawing benzodiazepines in primary care |journal=CNS Drugs |volume=23 |issue=1 |pages=19–34 |year=2009 |pmid=19062773 |doi=10.2165/0023210-200923010-00002 |s2cid=113206 }}

Benzodiazepines include:

alprazolam (Xanax), bromazepam,

chlordiazepoxide (Librium),

clonazepam (Klonopin),

diazepam (Valium),

lorazepam (Ativan),

oxazepam,

temazepam, and Triazolam.

Benzodiazepines lead to central nervous system depression, resulting in common adverse effects like drowsiness, oversedation, light-headedness. Memory impairment can be a common adverse effect especially in elderly, hypersalivation, ataxia, slurred speech, psychomotor effects.

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.{{cite journal |last1=Hayes |first1=Peggy E. |last2=Schulz |first2=S. Charles |title=Beta-blockers in anxiety disorders |journal=Journal of Affective Disorders |volume=13 |issue=2 |pages=119–30 |year=1987 |pmid=2890677 |doi=10.1016/0165-0327(87)90017-6 |url=https://zenodo.org/record/1258347 }}{{cite journal |doi=10.1001/archpsyc.1974.01760170071012 |pmid=4155284 |title=Beta-Adrenergic Receptor Blocking Drugs in Psychiatry |journal=Archives of General Psychiatry |volume=31 |issue=5 |pages=681–91 |year=1974 |last1=Jefferson |first1=James W. }} The alpha-1 antagonist prazosin could be effective for PTSD.{{cite journal |doi=10.1177/2045125313500982 |pmid=24490030 |pmc=3896131 |title=High-dose prazosin for the treatment of post-traumatic stress disorder |journal=Therapeutic Advances in Psychopharmacology |volume=4 |issue=1 |pages=43–7 |year=2013 |last1=Koola |first1=M. M. |last2=Varghese |first2=S. P. |last3=Fawcett |first3=J. A. }} The alpha-2 agonists clonidine and guanfacine have demonstrated both anxiolytic and anxiogenic effects.{{cite journal |doi=10.1001/archpsyc.1981.01780360094011 |pmid=7305609 |title=Effects of Clonidine on Anxiety Disorders |journal=Archives of General Psychiatry |volume=38 |issue=11 |pages=1278–82 |year=1981 |last1=Hoehn-Saric |first1=Rudolf |last2=Merchant |first2=A. F. |last3=Keyser |first3=M. L. |last4=Smith |first4=V. K. }}

Buspirone (Buspar) is a 5-HT_1A receptor agonist used to treated generalized anxiety disorder.[https://books.google.com/books?id=oJY8LrP_JysC&q=%22Azapirone%22+%225-HT1A%22+%22receptor%22+%22Sediel%22&pg=PA319 Annual Reports in Medicinal Chemistry, Volume 32 p. 319] If an individual has only recently stopped taking benzodiazepines, buspirone will be less effective.{{Cite journal |last1=DeMartinis |first1=N. |last2=Rynn |first2=M. |last3=Rickels |first3=K. |last4=Mandos |first4=L. |date=February 2000 |title=Prior benzodiazepine use and buspirone response in the treatment of generalized anxiety disorder |url=https://pubmed.ncbi.nlm.nih.gov/10732655/ |journal=The Journal of Clinical Psychiatry |volume=61 |issue=2 |pages=91–94 |doi=10.4088/jcp.v61n0203 |issn=0160-6689 |pmid=10732655}}

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.{{cite journal |doi=10.1586/14737175.7.7.769 |pmid=17610384 |title=Pregabalin for the treatment of generalized anxiety disorder: A novel pharmacologic intervention |journal=Expert Review of Neurotherapeutics |volume=7 |issue=7 |pages=769–81 |year=2014 |last1=Bandelow |first1=Borwin |last2=Wedekind |first2=Dirk |last3=Leon |first3=Teresa |s2cid=6229344 }}{{cite journal |doi=10.1358/dot.2007.43.9.1133188 |pmid=17940637 |title=Pregabalin: Its efficacy, safety and tolerability profile in generalized anxiety |journal=Drugs of Today |volume=43 |issue=9 |pages=601–10 |year=2007 |last1=Owen |first1=R.T. }}

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 generalized anxiety disorder.{{cite journal |doi=10.4088/JCP.v63n1112 |pmid=12444816 |title=Efficacy and Safety of Hydroxyzine in the Treatment of Generalized Anxiety Disorder |journal=The Journal of Clinical Psychiatry |volume=63 |issue=11 |pages=1020–7 |year=2002 |last1=Llorca |first1=Pierre-Michel |last2=Spadone |first2=Christian |last3=Sol |first3=Olivier |last4=Danniau |first4=Anne |last5=Bougerol |first5=Thierry |last6=Corruble |first6=Emmanuelle |last7=Faruch |first7=Michel |last8=Macher |first8=Jean-Paul |last9=Sermet |first9=Eric |last10=Servant |first10=Dominique }}

Phenibut (Anvifen, Fenibut, Noofen) is an anxiolytic{{Cite journal|last=Lapin|first=Izyaslav|date=2001|title=Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug|journal=CNS Drug Reviews|language=en|volume=7|issue=4|pages=471–481|doi=10.1111/j.1527-3458.2001.tb00211.x|issn=1527-3458|pmc=6494145|pmid=11830761}} used in Russia.{{Cite web|url=http://www.rmj.ru/articles/nevrologiya/Fenomen_aminofenilmaslyanoy_kisloty/|title=Феномен аминофенилмасляной кислоты|last=журнал»|first=Издание для практикующих врачей «Русский медицинский|website=www.rmj.ru|access-date=2018-12-19}} 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.{{Cite journal|date=2015-10-01|title=R-phenibut binds to the α2–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects|journal=Pharmacology Biochemistry and Behavior|language=en|volume=137|pages=23–29|doi=10.1016/j.pbb.2015.07.014|pmid=26234470|issn=0091-3057|last1=Zvejniece|first1=Liga|last2=Vavers|first2=Edijs|last3=Svalbe|first3=Baiba|last4=Veinberg|first4=Grigory|last5=Rizhanova|first5=Kristina|last6=Liepins|first6=Vilnis|last7=Kalvinsh|first7=Ivars|last8=Dambrova|first8=Maija|s2cid=42606053}} The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.{{Cite journal|last1=Owen|first1=David R.|last2=Wood|first2=David M.|last3=Archer|first3=John R. H.|last4=Dargan|first4=Paul I.|date=2016|title=Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity|journal=Drug and Alcohol Review|language=en|volume=35|issue=5|pages=591–596|doi=10.1111/dar.12356|pmid=26693960|issn=1465-3362|hdl=10044/1/30073|hdl-access=free}}{{cite journal |last1=Cohen |first1=Pieter A. |last2=Ellison |first2=Ross R. |last3=Travis |first3=John C. |last4=Gaufberg |first4=Slava V. |last5=Gerona |first5=Roy |title=Quantity of phenibut in dietary supplements before and after FDA warnings |journal=Clinical Toxicology |date=22 September 2021 |volume=60 |issue=4 |pages=486–488 |doi=10.1080/15563650.2021.1973020|pmid=34550038 |s2cid=237594860 }}

Temgicoluril (Mebicar) is an anxiolytic produced in Latvia and used in Eastern Europe. Temgicoluril has an effect on the structure of limbic-reticular activity, particularly on the hypothalamus, as well as on all four basic neuromediator systems – γ aminobutyric acid (GABA), choline, serotonin and adrenergic activity.{{cite web |title=Adaptol. Summary of Product Characteristics |url=http://olainfarm.lv/wp-content/uploads/2013/01/ADAPTOL_Summary-of-Product-Characteristics.pdf |access-date=24 July 2015 |archive-url=https://web.archive.org/web/20151203130342/http://olainfarm.lv/wp-content/uploads/2013/01/ADAPTOL_Summary-of-Product-Characteristics.pdf |archive-date=3 December 2015 |url-status=dead }} Temgicoluril decreases noradrenaline, increases serotonin, and exerts no effect on dopamine.{{cite journal |vauthors=Val'dman AV, Zaikonnikova IV, Kozlovskaia MM, Zimakova IE |title=[Characteristics of the psychotropic spectrum of action of mebicar] |language=ru |journal=Biulleten' Eksperimental'noĭ Biologii I Meditsiny |volume=89 |issue=5 |pages=568–70 |year=1980 |pmid=6104993 }}

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 receptor agonism thought to have some involvement.{{cite journal | last1 = Neznamov | first1 = GG | last2 = Siuniakov | first2 = SA | last3 = Chumakov | first3 = DV | last4 = Bochkarev | first4 = VK | last5 = Seredenin | first5 = SB | title = Clinical study of the selective anxiolytic agent afobazol | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 64 | issue = 2 | pages = 15–9 | year = 2001 | pmid = 11548440 }}{{cite journal | last1 = Silkina | first1 = IV | last2 = Gan'shina | first2 = TC | last3 = Seredin | first3 = SB | last4 = Mirzoian | first4 = RS | title = Gabaergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon | journal = Eksperimental'naia i Klinicheskaia Farmakologiia | volume = 68 | issue = 1 | pages = 20–4 | year = 2005 | pmid = 15786959 }}

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)).{{cite journal | vauthors = ((Vakhitova IuV)), Iamidanov RS, Seredinin SB | title = [Ladasten induces the expression of genes regulating dopamine biosynthesis in various structures of rat brain] | language = ru | journal = Eksp Klin Farmakol | volume = 67 | issue = 4 | pages = 7–11 | year = 2004 | pmid = 15500036 }}{{cite journal|last1=Vakhitova|first1=Yu. V.|last2=Yamidanov|first2=R. S.|last3=Vakhitov|first3=V. A.|last4=Seredenin|first4=S. B.|title=The effect of ladasten on gene expression in the rat brain|journal=Doklady Biochemistry and Biophysics|volume=401|issue=1–6|year=2005|pages=150–153|issn=1607-6729|doi=10.1007/s10628-005-0057-z|pmid=15999825|s2cid=28048257}}

Emoxypine is an antioxidant that is also a purported anxiolytic.{{cite journal |doi=10.1007/s10517-015-2855-3 |pmid=25894772 |title=Comparative Analysis of the Anxiolytic Effects of 3-Hydroxypyridine and Succinic Acid Derivatives |journal=Bulletin of Experimental Biology and Medicine |volume=158 |issue=6 |pages=756–61 |year=2015 |last1=Volchegorskii |first1=I. A. |last2=Miroshnichenko |first2=I. Yu. |last3=Rassokhina |first3=L. M. |last4=Faizullin |first4=R. M. |last5=Malkin |first5=M. P. |last6=Pryakhina |first6=K. E. |last7=Kalugina |first7=A. V. |s2cid=6052275 }}{{cite journal |doi=10.1007/s11055-012-9646-3 |id={{INIST|26388033}} |title=Antioxidant Treatment of Ischemic Brain Lesions |journal=Neuroscience and Behavioral Physiology |volume=42 |issue=8 |pages=842–5 |year=2012 |last1=Rumyantseva |first1=S. A. |last2=Fedin |first2=A. I. |last3=Sokhova |first3=O. N. |s2cid=39971165 }} Its chemical structure resembles that of pyridoxine, a form of vitamin B₆.

Menthyl isovalerate is a flavoring food additive marketed as a sedative and anxiolytic drug in Russia under the name Validol.{{cite encyclopedia | encyclopedia = The Great Soviet Encyclopedia | url = http://encyclopedia2.thefreedictionary.com/Validol | title = Validol}}{{cite web | title = Farmak Product Information - Validol | url = http://farmak.ua/assets_images/drugs/instruction/en/25/Validol_Product_Information.pdf | access-date = 9 April 2013 | archive-url = https://web.archive.org/web/20131219200018/http://farmak.ua/assets_images/drugs/instruction/en/25/Validol_Product_Information.pdf | archive-date = 19 December 2013 | url-status = dead }}

Some racetam based drugs such as aniracetam can have an antianxiety effect.{{cite journal |doi=10.2165/11319230-000000000-00000 |pmid=20166767 |title=Piracetam and Piracetam-Like Drugs |journal=Drugs |volume=70 |issue=3 |pages=287–312 |year=2010 |last1=Malykh |first1=Andrei G. |last2=Sadaie |first2=M. Reza |s2cid=12176745 }}

Alpidem is a nonbenzodiazepine anxiolytic with similar anxiolytic effectiveness as benzodiazepines but reduced sedation and cognitive, memory, and motor impairment.{{cite journal | vauthors = Skolnick P | title = Anxioselective anxiolytics: on a quest for the Holy Grail | journal = Trends Pharmacol Sci | volume = 33 | issue = 11 | pages = 611–20 | date = November 2012 | pmid = 22981367 | pmc = 3482271 | doi = 10.1016/j.tips.2012.08.003 | url = }} It was marketed briefly in France but was withdrawn from the market due to liver toxicity.

Etifoxine has similar anxiolytic effects as benzodiazepine drugs, but does not produce the same levels of sedation and ataxia.{{cite journal | last1=Nuss | first1=Philippe | last2=Ferreri | first2=Florian | last3=Bourin | first3=Michel | title= An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action (Review)|journal=Neuropsychiatric Disease and Treatment | volume=15 | year=2019 | issn=1178-2021 | pmid=31308671 | pmc=6615018 | doi=10.2147/ndt.s200568 | pages=1781–1795 | doi-access=free }} Further, etifoxine does not affect memory and vigilance, and does not induce rebound anxiety, drug dependence, or withdrawal symptoms.

Alcohol is sometimes used as an anxiolytic by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.{{cite journal |doi=10.1523/JNEUROSCI.0086-08.2008 |pmid=18448634 |pmc=2730732 |title=Why We Like to Drink: A Functional Magnetic Resonance Imaging Study of the Rewarding and Anxiolytic Effects of Alcohol |journal=Journal of Neuroscience |volume=28 |issue=18 |pages=4583–91 |year=2008 |last1=Gilman |first1=J. M. |last2=Ramchandani |first2=V. A. |last3=Davis |first3=M. B. |last4=Bjork |first4=J. M. |last5=Hommer |first5=D. W. }}

Cognitive behavioral 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.{{cite journal |doi=10.1016/j.pop.2007.05.002 |pmid=17868756 |title=Recent Advances in the Understanding and Treatment of Anxiety Disorders |journal=Primary Care: Clinics in Office Practice |volume=34 |issue=3 |pages=475–504, v–vi |year=2007 |last1=Shearer |first1=Steven L. }} Sometimes medication is combined with psychotherapy but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.{{cite journal |doi=10.1097/YCO.0b013e3280115e52 |pmid=17143079 |title=Combined pharmacotherapy and cognitive-behavioural therapy for anxiety disorders |journal=Current Opinion in Psychiatry |volume=20 |issue=1 |pages=30–5 |year=2007 |last1=Pull |first1=Charles B |s2cid=43737803 }}

If CBT is found ineffective, both the Canadian and American medical associations then suggest the use of medication.CMA & AMA Home medical guides 2012 & 2014 {{full citation needed|date=March 2018}}{{verify source|date=March 2018}}

• {{section link|ATC code N05|N05B Anxiolytics}}

{{See also for drug classes defined by psychological effects|Anxiolytics}}

{{Reflist}}

• {{Commons category-inline|Anxiolytics}}

{{Major Drug Groups}}

{{Anxiolytics}}

{{Chemical classes of psychoactive drugs}}

Category:Anxiety disorder treatment

Category:Drug classes defined by psychological effects