An anxiolytic (also antipanic or antianxiety agent) is a drug used for the treatment of anxiety, and its related psychological and physical symptoms. Anxiolytics have been shown to be useful in the treatment of anxiety disorders.
Anxiolytics are also known as minor tranquilizers. The term is less common in modern texts, and was originally derived from a dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.
Types of anxiolytics
Benzodiazepines are prescribed for short-term relief of severe and disabling anxiety. Benzodiazepines may also be indicated to cover the latent periods associated with the medications prescribed to treat an underlying anxiety disorder. They are used to treat a wide variety of conditions and symptoms and are usually a first choice when short-term CNS sedation is needed. Longer-term uses include treatment for severe anxiety. There is a risk of a benzodiazepine withdrawal and rebound syndrome after continuous usage for longer than two weeks, and tolerance and dependence may occur if patients stay under this treatment for longer. There is also the added problem of the accumulation of drug metabolites and adverse effects. Benzodiazepines include:
- Alprazolam (Xanax)
- Chlordiazepoxide (Librium)
- Clonazepam (Klonopin)
- Diazepam (Valium)
- Etizolam (Etilaam)
- Lorazepam (Ativan)
- Tofisopam (Emandaxin and Grandaxin) is a drug that is a benzodiazepine derivative. Like other benzodiazepines, it possesses anxiolytic properties, but, unlike other benzodiazepines, it does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing, or amnestic properties.
Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. SSRIs are primarily classified as antidepressants and typically higher dosages are required to be effective against anxiety disorders than to be effective against depression but nevertheless most SSRIs have anxiolytic properties, but are anxiogenic when first initiating treatment, and in some individuals continue to be anxiety-provoking. For this reason, a low dose of a benzodiazepine is often used for several weeks when initiating SSRI/SNRI therapy in order to counteract the initial anxiety caused by the drugs until the therapeutic delay of the SSRI/SNRI is finished and the drug becomes effective. Older tricyclic antidepressants (TCAs) are very anxiolytic as well, however, side effects are greater. Examples include: imipramine, doxepin, amitriptyline, and the unrelated trazodone. Mono-amine oxidase inhibitors (MAOIs) are very effective for anxiety, but due to drug dangers, are rarely prescribed. Examples include: Nardil and Parnate.
Azapirones are a class of 5-HT1A receptor agonists. They lack the sedation and the dependence associated with benzodiazepines and cause much less cognitive impairment. They may be less effective than benzodiazepines in patients who have been previously treated with benzodiazepines as they do not provide the sedation that these patients may expect or equate with anxiety relief. Currently approved azapirones include buspirone (Buspar) and tandospirone (Sediel). Gepirone (Ariza, Variza) is also in clinical development.
Barbiturates exert an anxiolytic effect linked to the sedation they cause. The risk of abuse and addiction is high. Many experts consider these drugs obsolete for treating anxiety but valuable for the short-term treatment of severe insomnia, though only after benzodiazepines or non-benzodiazepines have failed. They are rarely prescribed anymore.
Hydroxyzine (Atarax) is an old antihistamine originally approved for clinical use by the FDA in 1956. It possesses anxiolytic properties in addition to its antihistamine properties and is also licensed for the treatment of anxiety and tension. It is also used for its sedative properties as a premed before anesthesia or to induce sedation after anesthesia. It has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.
Pregabalin's therapeutic effect appears after 1 week of use and is similar in effectiveness to lorazepam, alprazolam, and venlafaxine, but pregabalin has demonstrated superiority by producing more consistent therapeutic effects for psychic and somatic anxiety symptoms. Long-term trials have shown continued effectiveness without the development of tolerance, and, in addition, unlike benzodiazepines, it does not disrupt sleep architecture and produces less severe cognitive and psychomotor impairment; it also has a low potential for abuse and dependence and may be preferred over the benzodiazepines for these reasons.
Certain natural substances are reputed to have anxiolytic properties, including the following:
- Bacopa monnieri (Brahmi)
- Lactuca virosa (Opium Lettuce)
- Rhodiola rosea (Arctic Weed/Golden Root)
- Hypericum perforatum (St. John's Wort)
- Matricaria recutita (German Chamomile)
- Mitragyna speciosa (Kratom)
- Piper methysticum (Kava)
- Sceletium tortuosum (Kanna)
- Scutellaria spp. (Skullcap)
- Valeriana officinalis (Valerian)
- Salvia splendens (Not to be confused with Salvia divinorum)
- Coriandrum sativum (Coriander) 
- Myristica (Nutmeg)
- Salvia Elegans (Pineapple Sage) 
- Inositol  In a double-blind, controlled trial, myo-inositol (18 grams daily) was superior to fluvoxamine for decreasing the number of panic attacks and had fewer side-effects.
- Cannabidiol (Marijuana) 
Over-the-counter pharmaceutical drugs
Picamilon is a prodrug formed by combining niacin with GABA that is able to cross the blood-brain barrier and is then hydrolyzed into GABA and niacin. It is theorized that the GABA released in this process activates GABA receptors, with potential to produce an anxiolytic response.  Picamilon is sold in the United States as a dietary supplement, while in Russia it is sold over the counter.
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.
Due to deficits with existing anxiolytics (either in terms of efficacy or side-effect profile), research into novel anxiolytics is active. Possible candidates for future drugs include:
Alternatives to medication
Psychotherapeutic treatment can be an effective alternative to medication. Exposure therapy is the recommended treatment for phobic anxiety disorders. Cognitive behavioral therapy (CBT) has been found to be effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive-compulsive disorder. Healthcare providers can also help by educating sufferers about anxiety disorders and referring individuals to self help resources. CBT has been shown to be effective in the treatment of generalized anxiety disorder, and possibly more effective than pharmacological treatments in the long term. Sometimes medication is combined with psychotherapy but research has found that there is no benefit of combined pharmacotherapy and psychotherapy versus monotherapy.
- ^ "antianxiety agent" at Dorland's Medical Dictionary
- ^ "anxiolytic (tranquilizer)". Memidex (WordNet) Dictionary/Thesaurus. http://www.memidex.com/anxiolytic+tranquilizer. Retrieved 2010-12-02.
- ^ 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 M, Veiga H, Deslandes A (June 2005). "[Neuromodulatory effects of caffeine and bromazepam on visual event-related potential (P300): a comparative study."]. Arq Neuropsiquiatr 63 (2B): 410–5. doi:10.1590/S0004-282X2005000300009. PMID 16059590. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-282X2005000300009&lng=en&nrm=iso&tlng=en.
- ^ Barlow, David H. Durand, V. Mark (2009). "Chapter 7: Mood Disorders and Suicide". Abnormal Psychology: An Integrative Approach (Fifth ed.). Belmont, CA: Wadsworth Cengage Learning. p. 239. ISBN 0495095567. OCLC 192055408.
- ^ medicine net. "hydroxyzine (Vistaril, Atarax)". medicinenet.com. http://www.medicinenet.com/hydroxyzine/article.htm. Retrieved 17 May 2008.
- ^ Llorca PM, Spadone C, Sol O (November 2002). "Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study". J Clin Psychiatry 63 (11): 1020–7. doi:10.4088/JCP.v63n1112. PMID 12444816. http://www.psychiatrist.com/privatepdf/2002/v63n11/v63n1112.pdf.
- ^ Bandelow, B.; Wedekind, D.; Leon, T. (Jul 2007). "Pregabalin for the treatment of generalized anxiety disorder: a novel pharmacologic intervention.". Expert Rev Neurother 7 (7): 769–81. doi:10.1586/1473718.104.22.1689. PMID 17610384.
- ^ Owen, RT. (Sep 2007). "Pregabalin: its efficacy, safety and tolerability profile in generalized anxiety.". Drugs Today (Barc) 43 (9): 601–10. doi:10.1358/dot.2007.43.9.1133188. PMID 17940637.
- ^ . PMID 12652886.
- ^ Emamghoreishi M, Khasaki M, Aazam MF (2005). "Coriandrum sativum: evaluation of its anxiolytic effect in the elevated plus-maze". Journal of Ethnopharmacology 96 (3): 365–370. doi:10.1016/j.jep.2004.06.022. PMID 15619553.
- ^  Maribel Herrera-Ruiza, Yolanda García-Beltrána, Sergio Morab, Gabriela Díaz-Vélizb, Glauce S.B. Vianac, Jaime Tortorielloa, Guillermo Ramíreza, "Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans", Journal of Ethnopharmacology, Vol. 107, No. 1, pp. 53-58 (Aug. 2006)
- ^ Fux M, Levine J, Aviv A, Belmaker RH (1996). "Inositol treatment of obsessive-compulsive disorder". American Journal of Psychiatry 153 (9): 1219–1221. PMID 8780431.
- ^ Palatnik A, Frolov K, Fux M, Benjamin J (2001). "Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder". Journal of Clinical Psychopharmacology 21 (3): 335–339. doi:10.1097/00004714-200106000-00014. PMID 11386498.
- ^ Zuardi, A.W; Crippa, JA; Hallak, JE; Moreira, FA; Guimarães, FS (2006). "Cannabidiol as an antipsychotic drug" (PDF). Brazilian Journal of Medical and Biological Research 39 (4): 421–429. doi:10.1590/S0100-879X2006000400001. ISSN 0100-879X ISSN 0100-879X. PMID 16612464. http://www.scielo.br/pdf/bjmbr/v39n4/6164.pdf.
- ^ Shephard RA (June 1987). "Behavioral effects of GABA agonists in relation to anxiety and benzodiazepine action". Life Sci. 40 (25): 2429–36. doi:10.1016/0024-3205(87)90758-2. PMID 2884549.
- ^ Foster AC, Kemp JA (February 2006). "Glutamate- and GABA-based CNS therapeutics". Curr Opin Pharmacol 6 (1): 7–17. doi:10.1016/j.coph.2005.11.005. PMID 16377242.
- ^ Psychopharmacology (Berl). 2009 Oct 13;doi:10.1007/s00213-009-1695-0 http://www.anxietyinsights.info/abstract_chlorpheniramine_exerts_anxiolyticlike_effects_an.htm
- ^ Zwanzger, P.; Deckert, J. (Mar 2007). "[Anxiety disorders. Causes, clinical picture and treatment]". Nervenarzt 78 (3): 349–59; quiz 360. doi:10.1007/s00115-006-2202-z. PMID 17279399.
- ^ Shearer, SL. (Sep 2007). "Recent advances in the understanding and treatment of anxiety disorders.". Prim Care 34 (3): 475–504, v–vi. doi:10.1016/j.pop.2007.05.002. PMID 17868756.
- ^ Gould, RA; Otto, M; Pollack, M; Yap, L (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. http://www.sciencedirect.com/science/article/B7XMW-4JCS59S-7/2/68c4515f717b005757a92ea0e0c7b488. Retrieved 8 November 2008.
- ^ Pull, CB. (Jan 2007). "Combined pharmacotherapy and cognitive-behavioural therapy for anxiety disorders". Curr Opin Psychiatry 20 (1): 30–5. doi:10.1097/YCO.0b013e3280115e52. PMID 17143079.
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