Anxiolytic

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

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. 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.[2]

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.[3] Tolerance and dependence may occur.[4] The risk of abuse in this class of medication is smaller than in that of barbiturates. Cognitive and behavioral adverse effects are possible.[5]

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 escitalopram and SNRIs venlafaxine and duloxetine are USFDA approved to treat generalized 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.[6][7] 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.[8]

Tricyclic antidepressants

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 fewer adverse effects. Examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine.[9][10]

Tetracyclic antidepressant

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.

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.[11]

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.[12][13] The Alpha-1 agonist prazosin could be effective for PTSD.[14] The Alpha-2 agonists clonidine and guanfacine have demonstrated both anxiolytic and anxiogenic effects.[15]

Miscellaneous

Buspirone

Buspirone (Buspar) is a 5-HT1A receptor agonist used to treated generalized anxiety disorder. If an individual has taken a benzodiazepine, buspirone will be less effective.[16]

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.[17][18]

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 generalized anxiety disorder.[19]

Phenibut

Phenibut (Anvifen, Fenibut, Noofen) is an anxiolytic[20] used in Russia.[21] Phenibut is a GABAB receptor agonist,[20] as well as an antagonist at α2δ subunit-containing voltage-dependent calcium channels (VDCCs), similarly to gabapentinoids like gabapentin and pregabalin.[22] The medication is not approved by the FDA for use in the United States, but is sold online as a supplement.[23][24]

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.[25] Mebicar decreases noradrenaline, increases serotonin, and exerts no effect on dopamine.[26]

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.[27][28]

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).[29][30]

Emoxypine

Emoxypine is an antioxidant that is also a purported anxiolytic.[31][32] Its chemical structure resembles that of pyridoxine, a form of vitamin B6.

Menthyl isovalerate

Menthyl isovalerate is a flavoring food additive marketed as a sedative and anxiolytic drug in Russia under the name Validol.[33][34]

Racetams

Some racetam based drugs such as aniracetam can have an antianxiety effect.[35]

Etifoxine

Etifoxine has similar anxiolytic effects as benzodiazepine drugs, but does not produce the same levels of sedation and ataxia.[36] Further, etifoxine does not affect memory and vigilance, and does not induce rebound anxiety, drug dependence, or withdrawal symptoms.[36]

Alcohol

Alcohol is sometimes used as an anxiolytic by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.[37]

Alternatives to medication

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.[38] Sometimes medication is combined with psychotherapy but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.[39]

If CBT is found ineffective, both the Canadian and American medical associations then suggest the use of medication.[40]

See also

Categories

Anxiolytics
Drug classes defined by psychological effects
Drugs by psychological effects
Psychoactive drugs

References

  1. ↑ "antianxiety agent" at Dorland's Medical Dictionary
  2. ↑ Burchum, Jacqueline Rosenjack; Rosenthal, Laura D. (29 January 2015). Lehne's pharmacology for nursing care (9th ed.). St. Louis, Missouri. ISBN 9780323321907. OCLC 890310283.
  3. ↑ Cassano, Giovanni B.; Rossi, Nicolò Baldini; Pini, Stefano (2002). "Psychopharmacology of anxiety disorders". Dialogues in Clinical Neuroscience. 4 (3): 271–285. doi:10.31887/DCNS.2002.4.3/gcassano. ISSN 1294-8322. PMC 3181684. PMID 22033867.
  4. ↑ Gelder, M, Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp236.
  5. ↑ Lader M, Tylee A, Donoghue J (2009). "Withdrawing benzodiazepines in primary care". CNS Drugs. 23 (1): 19–34. doi:10.2165/0023210-200923010-00002. PMID 19062773. S2CID 113206.
  6. ↑ Kanba, S. (2004). "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 of Psychiatry & Neuroscience. 29 (6): 485. PMC 524966. PMID 15644990.
  7. ↑ Barlow, David H.; Durand, Mark V (2009). "Chapter 7: Mood Disorders and Suicide". Abnormal Psychology: An Integrative Approach (Fifth ed.). Belmont, CA: Wadsworth Cengage Learning. p. 239. ISBN 978-0-495-09556-9. OCLC 192055408.
  8. ↑ John Vanin; James Helsley (19 June 2008). Anxiety Disorders: A Pocket Guide For Primary Care. Springer Science & Business Media. p. 189.
  9. ↑ Post, Jason W.; Migne, Louis J. (2012). Antidepressants : Pharmacology, Health Effects and Controversy. New York: Nova Science Publishers. p. 58. ISBN 9781620815557.
  10. ↑ "Tricyclic antidepressants (TCAs)". Mayo Clinic.
  11. ↑ Tanghe, A.; Geerts, S.; Van Dorpe, J.; Brichard, B.; Bruhwyler, J.; Géczy, J. (August 1997). "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". Acta Psychiatrica Scandinavica. 96 (2): 134–141. doi:10.1111/j.1600-0447.1997.tb09918.x. ISSN 0001-690X. PMID 9272198. S2CID 23485112.
  12. ↑ Hayes, Peggy E.; Schulz, S. Charles (1987). "Beta-blockers in anxiety disorders". Journal of Affective Disorders. 13 (2): 119–30. doi:10.1016/0165-0327(87)90017-6. PMID 2890677.
  13. ↑ Jefferson, James W. (1974). "Beta-Adrenergic Receptor Blocking Drugs in Psychiatry". Archives of General Psychiatry. 31 (5): 681–91. doi:10.1001/archpsyc.1974.01760170071012. PMID 4155284.
  14. ↑ Koola, M. M.; Varghese, S. P.; Fawcett, J. A. (2013). "High-dose prazosin for the treatment of post-traumatic stress disorder". Therapeutic Advances in Psychopharmacology. 4 (1): 43–7. doi:10.1177/2045125313500982. PMC 3896131. PMID 24490030.
  15. ↑ Hoehn-Saric, Rudolf; Merchant, A. F.; Keyser, M. L.; Smith, V. K. (1981). "Effects of Clonidine on Anxiety Disorders". Archives of General Psychiatry. 38 (11): 1278–82. doi:10.1001/archpsyc.1981.01780360094011. PMID 7305609.
  16. ↑ Annual Reports in Medicinal Chemistry, Volume 32 p. 319
  17. ↑ Bandelow, Borwin; Wedekind, Dirk; Leon, Teresa (2014). "Pregabalin for the treatment of generalized anxiety disorder: A novel pharmacologic intervention". Expert Review of Neurotherapeutics. 7 (7): 769–81. doi:10.1586/14737175.7.7.769. PMID 17610384. S2CID 6229344.
  18. ↑ Owen, R.T. (2007). "Pregabalin: Its efficacy, safety and tolerability profile in generalized anxiety". Drugs of Today. 43 (9): 601–10. doi:10.1358/dot.2007.43.9.1133188. PMID 17940637.
  19. ↑ Llorca, Pierre-Michel; Spadone, Christian; Sol, Olivier; Danniau, Anne; Bougerol, Thierry; Corruble, Emmanuelle; Faruch, Michel; Macher, Jean-Paul; Sermet, Eric; Servant, Dominique (2002). "Efficacy and Safety of Hydroxyzine in the Treatment of Generalized Anxiety Disorder". The Journal of Clinical Psychiatry. 63 (11): 1020–7. doi:10.4088/JCP.v63n1112. PMID 12444816.
  20. 1 2 Lapin, Izyaslav (2001). "Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug". CNS Drug Reviews. 7 (4): 471–481. doi:10.1111/j.1527-3458.2001.tb00211.x. ISSN 1527-3458. PMC 6494145. PMID 11830761.
  21. ↑ журнал», Издание для практикующих врачей «Русский медицинский. "Феномен аминофенилмасляной кислоты". www.rmj.ru. Retrieved 19 December 2018.
  22. ↑ Zvejniece, Liga; Vavers, Edijs; Svalbe, Baiba; Veinberg, Grigory; Rizhanova, Kristina; Liepins, Vilnis; Kalvinsh, Ivars; Dambrova, Maija (1 October 2015). "R-phenibut binds to the α2–δ subunit of voltage-dependent calcium channels and exerts gabapentin-like anti-nociceptive effects". Pharmacology Biochemistry and Behavior. 137: 23–29. doi:10.1016/j.pbb.2015.07.014. ISSN 0091-3057. PMID 26234470. S2CID 42606053.
  23. ↑ Owen, David R.; Wood, David M.; Archer, John R. H.; Dargan, Paul I. (2016). "Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity". Drug and Alcohol Review. 35 (5): 591–596. doi:10.1111/dar.12356. hdl:10044/1/30073. ISSN 1465-3362. PMID 26693960.
  24. ↑ Cohen, Pieter A.; Ellison, Ross R.; Travis, John C.; Gaufberg, Slava V.; Gerona, Roy (22 September 2021). "Quantity of phenibut in dietary supplements before and after FDA warnings". Clinical Toxicology: 1–3. doi:10.1080/15563650.2021.1973020. PMID 34550038. S2CID 237594860.
  25. ↑ "Adaptol. Summary of Product Characteristics" (PDF). Archived from the original (PDF) on 3 December 2015. Retrieved 24 July 2015.
  26. ↑ Val'dman AV, Zaikonnikova IV, Kozlovskaia MM, Zimakova IE (1980). "[Characteristics of the psychotropic spectrum of action of mebicar]". Biulleten' Eksperimental'noĭ Biologii I Meditsiny (in Russian). 89 (5): 568–70. PMID 6104993.
  27. ↑ Neznamov, GG; Siuniakov, SA; Chumakov, DV; Bochkarev, VK; Seredenin, SB (2001). "Clinical study of the selective anxiolytic agent afobazol". Eksperimental'naia i Klinicheskaia Farmakologiia. 64 (2): 15–9. PMID 11548440.
  28. ↑ Silkina, IV; Gan'shina, TC; Seredin, SB; Mirzoian, RS (2005). "Gabaergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon". Eksperimental'naia i Klinicheskaia Farmakologiia. 68 (1): 20–4. PMID 15786959.
  29. ↑ Vakhitova IuV, Iamidanov RS, Seredinin SB (2004). "[Ladasten induces the expression of genes regulating dopamine biosynthesis in various structures of rat brain]". Eksp Klin Farmakol (in Russian). 67 (4): 7–11. PMID 15500036.
  30. ↑ Vakhitova, Yu. V.; Yamidanov, R. S.; Vakhitov, V. A.; Seredenin, S. B. (2005). "The effect of ladasten on gene expression in the rat brain". Doklady Biochemistry and Biophysics. 401 (1–6): 150–153. doi:10.1007/s10628-005-0057-z. ISSN 1607-6729. PMID 15999825. S2CID 28048257.
  31. ↑ Volchegorskii, I. A.; Miroshnichenko, I. Yu.; Rassokhina, L. M.; Faizullin, R. M.; Malkin, M. P.; Pryakhina, K. E.; Kalugina, A. V. (2015). "Comparative Analysis of the Anxiolytic Effects of 3-Hydroxypyridine and Succinic Acid Derivatives". Bulletin of Experimental Biology and Medicine. 158 (6): 756–61. doi:10.1007/s10517-015-2855-3. PMID 25894772. S2CID 6052275.
  32. ↑ Rumyantseva, S. A.; Fedin, A. I.; Sokhova, O. N. (2012). "Antioxidant Treatment of Ischemic Brain Lesions". Neuroscience and Behavioral Physiology. 42 (8): 842–5. doi:10.1007/s11055-012-9646-3. S2CID 39971165. INIST:26388033.
  33. ↑ "Validol". The Great Soviet Encyclopedia.
  34. ↑ "Farmak Product Information - Validol" (PDF). Archived from the original (PDF) on 19 December 2013. Retrieved 9 April 2013.
  35. ↑ Malykh, Andrei G.; Sadaie, M. Reza (2010). "Piracetam and Piracetam-Like Drugs". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767. S2CID 12176745.
  36. 1 2 Nuss, Philippe; Ferreri, Florian; Bourin, Michel (2019). "An update on the anxiolytic and neuroprotective properties of etifoxine: from brain GABA modulation to a whole-body mode of action (Review)". Neuropsychiatric Disease and Treatment. 15: 1781–1795. doi:10.2147/ndt.s200568. ISSN 1178-2021. PMC 6615018. PMID 31308671.
  37. ↑ Gilman, J. M.; Ramchandani, V. A.; Davis, M. B.; Bjork, J. M.; Hommer, D. W. (2008). "Why We Like to Drink: A Functional Magnetic Resonance Imaging Study of the Rewarding and Anxiolytic Effects of Alcohol". Journal of Neuroscience. 28 (18): 4583–91. doi:10.1523/JNEUROSCI.0086-08.2008. PMC 2730732. PMID 18448634.
  38. ↑ Shearer, Steven L. (2007). "Recent Advances in the Understanding and Treatment of Anxiety Disorders". Primary Care: Clinics in Office Practice. 34 (3): 475–504, v–vi. doi:10.1016/j.pop.2007.05.002. PMID 17868756.
  39. ↑ Pull, Charles B (2007). "Combined pharmacotherapy and cognitive-behavioural therapy for anxiety disorders". Current Opinion in Psychiatry. 20 (1): 30–5. doi:10.1097/YCO.0b013e3280115e52. PMID 17143079. S2CID 43737803.
  40. ↑ CMA & AMA Home medical guides 2012 & 2014
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