An anxiolytic (also antipanic or antianxiety agent) is a medication or other intervention that inhibits 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 (also known as ethanol) 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.
|Synonyms||sedative, minor tranquilizer|
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.
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.
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. Tolerance and dependence may also occur, but may be clinically acceptable, also the risk of abuse is significantly smaller than in case of barbiturates. Cognitive and behavioral adverse effects are possible. Benzodiazepines include:
- Alprazolam (Xanax)
- Bromazepam (Lectopam, Lexotan)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin, Rivotril)
- Clorazepate (Tranxene)
- Diazepam (Valium)
- Flurazepam (Dalmane)
- Lorazepam (Ativan)
- Oxazepam (Serax, Serapax)
- Temazepam (Restoril)
- Triazolam (Halcion)
- 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.
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.
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. Hydroxyzine has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.
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.
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.
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.
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.
Selective serotonin reuptake inhibitorsEdit
Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitors (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, although at higher dosages than used to treat depression. 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 inhibitorsEdit
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 (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.
Mirtazapine has demonstrated anxiolytic effects with a better side effect profile to all other classes of antidepressants, for example it rarely causes or exacerbates anxiety. However, in many countries (such as USA and Australia), it is not specifically approved for anxiety disorders and is used off label.
Monoamine oxidase inhibitorsEdit
Monoamine oxidase inhibitors (MAOIs) are effective for anxiety, but their dietary restrictions, side effects and availability of newer effective drugs, have limited their use. 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 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.
Phenibut (brand names Anvifen, Fenibut, Noofen) is an anxiolytic used in Russia. Phenibut is a GABAB 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 (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. Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, and increases the brain serotonin level.
Fabomotizole (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. It has yet to find clinical use outside of Russia.
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.[medical citation needed]
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.
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.
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).
Alternatives to medicationEdit
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 not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.
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 alprazolam and an antidepressant, usually Prozac for its effectiveness.[verification needed]
- "antianxiety agent" at Dorland's Medical Dictionary
- Youngstedt, Shawn D.; Kripke, Daniel F. (2007). "Does bright light have an anxiolytic effect? – an open trial". BMC Psychiatry. 7: 62. doi:10.1186/1471-244X-7-62. PMC 2194679. PMID 17971237.
- 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.
- "anxiolytic (tranquilizer)". Memidex (WordNet) Dictionary/Thesaurus. Retrieved 2 December 2010.
- Finkel RF, Clark MA, Cubeddu LX (2009). Pharmacology. Lippincott Williams & Wilkins. p. 151. ISBN 9780781771559. Archived from the original on 1 April 2017.
- Galanter, Marc (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (American Psychiatric Press Textbook of Substance Abuse Treatment) (4 ed.). American Psychiatric Publishing, Inc. p. 197. ISBN 978-1-58562-276-4.
- Burchum, Jacqueline Rosenjack; Rosenthal, Laura D. (29 January 2015). Lehne's pharmacology for nursing care (9th ed.). St. Louis, Missouri. ISBN 9780323321907. OCLC 890310283.
- Cassano, Giovanni B.; Rossi, Nicolò Baldini; Pini, Stefano (2002). "Psychopharmacology of anxiety disorders". Dialogues in Clinical Neuroscience. 4 (3): 271–285. ISSN 1294-8322. PMC 3181684. PMID 22033867.
- Gelder, M, Mayou, R. and Geddes, J. 2005. Psychiatry. 3rd ed. New York: Oxford. pp236.
- 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.
- Montenegro, Mariana; Veiga, Heloisa; Deslandes, Andréa; Cagy, Maurício; McDowell, Kaleb; Pompeu, Fernando; Piedade, Roberto; Ribeiro, Pedro (2005). "Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): A comparative study". Arquivos de Neuro-Psiquiatria. 63 (2b): 410–5. doi:10.1590/S0004-282X2005000300009. PMID 16059590.
- medicine net. "hydroxyzine (Vistaril, Atarax)". medicinenet.com. Archived from the original on 13 May 2008. Retrieved 17 May 2008.
- 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.
- Miyata, Shigeo; Hirano, Shoko; Ohsawa, Masahiro; Kamei, Junzo (2009). "Chlorpheniramine exerts anxiolytic-like effects and activates prefrontal 5-HT systems in mice". Psychopharmacology. 213 (2–3): 441–52. doi:10.1007/s00213-009-1695-0. PMID 19823805.
- "Heroin addiction and anxiety disorder". DualDiagnosis. Retrieved 16 April 2016.
- Liddell, Malcolm B.; Aziz, Victor; Briggs, Patrick; Kanakkehewa, Nimalee; Rawi, Omar (2013). "Buprenorphine augmentation in the treatment of refractory obsessive–compulsive disorder". Therapeutic Advances in Psychopharmacology. 3 (1): 15–9. doi:10.1177/2045125312462233. PMC 3736962. PMID 23983988.
- 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.[page needed]
- John Vanin; James Helsley (19 June 2008). Anxiety Disorders: A Pocket Guide For Primary Care. Springer Science & Business Media. p. 189.
- Post, Jason W.; Migne, Louis J. (2012). Antidepressants : Pharmacology, Health Effects and Controversy. New York: Nova Science Publishers. p. 58. ISBN 9781620815557.
- 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.
- Noyes, Russell (1982). "Beta-blocking drugs and anxiety". Psychosomatics. 23 (2): 155–70. doi:10.1016/s0033-3182(82)73433-4. PMID 6122234.
- 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.
- http://www.medscape.com/viewarticle/760070[full citation needed]
- 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.
- 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.
- журнал», Издание для практикующих врачей «Русский медицинский. "Феномен аминофенилмасляной кислоты". www.rmj.ru. Retrieved 19 December 2018.
- 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.
- 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. ISSN 1465-3362. PMID 26693960.
- "Adaptol. Summary of Product Characteristics" (PDF). Retrieved 24 July 2015.
- 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.
- "International Nonproprietary Names for Pharmaceutical Substances (INN)" (PDF). WHO Drug Information. 26 (1): 63. 2012. Retrieved 21 March 2015.
- 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.
- 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.
- Seredin, SB; Melkumian, DS; Val'dman, EA; Iarkova, MA; Seredina, TC; Voronin, MV; Lapitskaia, AS (2006). "Effects of afobazole on the BDNF content in brain structures of inbred mice with different phenotypes of emotional stress reaction". Eksperimental'naia I Klinicheskaia Farmakologiia. 69 (3): 3–6. PMID 16878488.
- Antipova TA, Sapozhnikova DS, Bakhtina LI, Seredenin SB (2009). "[Selective anxiolytic afobazole increases the content of BDNF and NGF in cultured hippocampal HT-22 line neurons]". Eksperimental'naia I Klinicheskaia Farmakologiia (in Russian). 72 (1): 12–4. PMID 19334503.
- Seredenin, S. B.; Antipova, T. A.; Voronin, M. V.; Kurchashova, S. Yu.; Kuimov, A. N. (2009). "Interaction of Afobazole with σ1-Receptors". Bulletin of Experimental Biology and Medicine. 148 (1): 42–4. doi:10.1007/s10517-009-0624-x. PMID 19902093.
- 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.
- 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. INIST:26388033.
- Annual Reports in Medicinal Chemistry, Volume 32 p. 319
- 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:10.1586/14737188.8.131.529. PMID 17610384.
- 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.
- "Validol". The Great Soviet Encyclopedia.
- "Farmak Product Information - Validol" (PDF).
- Banchs, Richard J.; Lerman, Jerrold (2014). "Preoperative Anxiety Management, Emergence Delirium, and Postoperative Behavior". Anesthesiology Clinics. 32 (1): 1–23. doi:10.1016/j.anclin.2013.10.011. PMID 24491647.
- Vasileiou, Ioanna; Xanthos, Theodoros; Koudouna, Eleni; Perrea, Despoina; Klonaris, Chris; Katsargyris, Athanasios; Papadimitriou, Lila (2009). "Propofol: A review of its non-anaesthetic effects". European Journal of Pharmacology. 605 (1–3): 1–8. doi:10.1016/j.ejphar.2009.01.007. PMID 19248246.
- 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.
- 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.
- "Alcohol and Sleep". National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health.
- Howard, Matthew O.; Bowen, Scott E.; Garland, Eric L.; Perron, Brian E.; Vaughn, Michael G. (2011). "Inhalant use and inhalant use disorders in the United States". Addiction Science & Clinical Practice. 6 (1): 18–31. PMC 3188822. PMID 22003419.
- Zwanzger, P.; Deckert, J. (2007). "Angsterkrankungen". Der Nervenarzt. 78 (3): 349–59, quiz 360. doi:10.1007/s00115-006-2202-z. PMID 17279399.
- 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.
- Gould, Robert A.; Otto, Michael W.; Pollack, Mark H.; Yap, Liang (1997). "Cognitive behavioral and pharmacological treatment of generalized anxiety disorder: A preliminary meta-analysis". Behavior Therapy. 28 (2): 285–305. doi:10.1016/S0005-7894(97)80048-2. INIST:2831082.
- 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.
- CMA & AMA Home medical guides 2012 & 2014[full citation needed]
- Media related to Anxiolytics at Wikimedia Commons