This article has multiple issues. Please help improve it or discuss these issues on the talk page. (Learn how and when to remove these template messages)(Learn how and when to remove this template message)
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 ethanol (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. Anxiolytics have been shown to be useful in the treatment of anxiety disorder. Light therapy and other interventions have also been found to have an anxiolytic effect.
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.
- 1 Medications
- 1.1 Barbiturates
- 1.2 Benzodiazepines
- 1.3 Carbamates
- 1.4 Opioids
- 1.5 Antidepressants
- 1.6 Sympatholytics
- 1.7 Miscellaneous
- 1.8 Herbal preparations
- 1.9 Supplements and over-the-counter pharmaceutical drugs
- 1.10 Future drugs
- 1.11 Common drugs
- 2 Alternatives to medication
- 3 See also
- 4 References
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 or episodic 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. 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. 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.
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 Diamorphine, 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.
Because of their high potential for abuse and high overdose rates, prescribing opioids for mental health issues is very uncommon and frowned upon within the medical community. Safer opioids which are less likely to be abused, have less deadly drug interactions, and are less likely to cause overdose are the ones that are being looked into the most for their anxiolytic-type properties. Given that many anxiety sufferers are more prone to alcohol and opioid addiction, the potential danger in prescribing opioids is apparent. Benzodiazepines are very similar to alcohol in how they impact the user and the brain, and even though anxiety sufferers are more prone to alcohol addiction these drugs are still prescribed. The same logic is being used in the push to get opioids used for anxiety treatment. Opioids and benzodiazepines are very dangerous to use together, and using them together is one of the most common reasons for accidental mixed drug overdose in the United States, so great caution should be taken if opioid prescriptions for anxiety become more accepted.
It appears that buprenorphine is gaining some acceptability within in the medical community for being used to treat 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 much safer than methadone and lots of other opioids and has a very long half-life leading to less compulsive use among those who attempt to abuse it or become mentally addicted to 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 inhibitors
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 inhibitors
Serotonin–norepinephrine reuptake inhibitor include venlafaxine and duloxetine drugs. Venlafaxine, in extended release form, and duloxetine, are indicated for the treatment of GAD. SSNRIs 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, 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 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. 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.
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.
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. However, in practice, hydroxyzine is rarely as efficacious as the benzodiazepines.
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.
Menthyl isovalerate is a flavoring food additive which is marketed as a sedative and anxiolytic drug in Russia under the name Validol. Sublingual administration of Validol produces a sedative effect, and has moderate reflex and vascular dilative action caused by stimulation of sensory nerve receptors of the oral mucosa followed by the release of endorphins. Validol is typically administered as needed for symptom relief.
||This section needs more medical references for verification or relies too heavily on primary sources. (November 2016)|
Certain natural substances are reputed to have anxiolytic properties, including the following:
- Garcinia indica (Kokum)
- Scutellaria baicalensis
- Scutellaria galericulata
- Scutellaria lateriflora
- Coriandrum sativum (Coriander)
- Salvia elegans (Pineapple Sage)
- Cannabidiol (a cannabinoid found in marijuana)
Supplements and 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 was sold in the United States as a dietary supplement until November 2015, while in Russia it is sold as a prescription drug.
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.
Melatonin has anxiolytic properties, likely through interactions between GABAA and melatonin2 (MTNR1B) receptors activating the GABAergic system. It has been used experimentally as an effective premedication for general anesthesia in surgical procedures, replacing the benzodiazepine midazolam.
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:
Prescription-free drugs are often poor anxiolytics and often worsen the symptoms over time. However, they are often used for self-medication because of their wide availability (e.g. alcoholic beverages).
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 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 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.[unreliable source][original research?]
Note that adolescent anxiety once the patient becomes pubescent can often turn into depression, at which time other treatments may be required.
Transcendental Meditation technique shows marked efficacy in treating anxiety disorders says a meta-analysis of randomized controlled trials, "TM practice is more effective than treatment as usual and most alternative treatments, with greatest effects observed in individuals with high anxiety" And a meta-analysis says: "Differential effects of relaxation techniques on trait anxiety: a meta-analysis. Effect sizes for the different treatments (e.g., Progressive Relaxation, EMG Biofeedback, various forms of meditation, etc.) were calculated. Most of the treatments produced similar effect sizes except that Transcendental Meditation had significantly larger effect size (p less than .005)"
Regular practice of Transcendental Meditation enables some active duty service members battling post-traumatic stress disorder to reduce or even eliminate their psychotropic medication and get better control of their often-debilitating symptoms, researchers report in the journal Military Medicine.
- "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 . 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 2010-12-02.
- 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.
- 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 . 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.
- "Heroin addiction and anxiety disorder". DualDiagnosis. Retrieved 16 April 2016.
- Liddell MB, Aziz V, Briggs P, Kanakkehewa N, Rawi O (2013). "Buprenorphine augmentation in the treatment of refractory obsessive-compulsive disorder". Therapeutic Advances in Psychopharmacology. 3 (1): 15–9. doi:10.1177/2045125312462233. PMC . 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 0-495-09556-7. 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.
- Jefferson, J. W. (1974). "Beta-adrenergic receptor blocking drugs in psychiatry". Archives of General Psychiatry. 31 (5): 681. doi:10.1001/archpsyc.1974.01760170071012.
- Noyes Jr, R (1982). "Beta-blocking drugs and anxiety". Psychosomatics. 23 (2): 155–170. doi:10.1016/s0033-3182(82)73433-4.
- Koola MM, Varghese SP, Fawcett JA (2014). "High-dose prazosin for the treatment of post-traumatic stress disorder". Therapeutic Advances in Psychopharmacology. 4 (1): 43–7. doi:10.1177/2045125313500982. PMC . PMID 24490030.
- http://www.medscape.com/viewarticle/760070[full citation needed]
- Hoehn-Saric R, Merchant AF, Keyser ML, Smith VK (1981). "Effects of clonidine on anxiety disorders". Archives of General Psychiatry. 38 (11): 1278–82. doi:10.1001/archpsyc.1981.01780360094011. PMID 7305609.
- "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, SB; Antipova, TA; Voronin, MV; Kurchashova, SY; Kuimov, AN (2009). "Interaction of afobazole with sigma1-receptors". Bulletin of experimental biology and medicine. 148 (1): 42–4. doi:10.1007/s10517-009-0624-x. PMID 19902093.
- I. A. Volchegorskii; et al. (April 2015). "Comparative Analysis of the Anxiolytic Effects of 3-Hydroxypyridine and Succinic Acid Derivatives". Bulletin of Experimental Biology and Medicine. 158 (6): 756–761. doi:10.1007/s10517-015-2855-3.
- S. A. Rumyantseva A.; I. Fedin; O. N. Sokhova (October 2012). "Antioxidant Treatment of Ischemic Brain Lesions". Neuroscience and Behavioral Physiology. 42 (8): 842–845. doi:10.1007/s11055-012-9646-3.
- medicine net. "hydroxyzine (Vistaril, Atarax)". medicinenet.com. Archived from the original on 13 May 2008. 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.
- 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:10.1586/1473722.214.171.1249. 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.
- The Great Soviet Encyclopedia http://encyclopedia2.thefreedictionary.com/Validol[full citation needed]
- Farmak Product Information - Validol http://farmak.ua/assets_images/drugs/instruction/en/25/Validol_Product_Information.pdf[full citation needed]
- Itop Doctor http://doctor.itop.net/DirectoryItem.aspx?DirId=1&ItemId=268[full citation needed]
- Banchs, Richard J.; Lerman, Jerrold (2014-03-01). "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 (2009-03-01). "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 AG; Sadaie MR (Feb 2010). "Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders.". Drugs. 70 (3): 287–312. doi:10.2165/11319230-000000000-00000. PMID 20166767.
- Patel, Manish; Antala, Bhavesh; Barua, Chandana; Lahkar, Mangala (2013). "Anxiolytic activity of aqueous extract of Garcinia indica in mice". International Journal of Green Pharmacy. 7 (4): 332–35. doi:10.4103/0973-8258.122089.[permanent dead link]
- Wolfson, P; Hoffmann, DL (2003). "An investigation into the efficacy of Scutellaria lateriflora in healthy volunteers". Alternative therapies in health and medicine. 9 (2): 74–8. 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.
- Herrera-Ruiz, Maribel; García-Beltrán, Yolanda; Mora, Sergio; Díaz-Véliz, Gabriela; Viana, Glauce S.B.; Tortoriello, Jaime; Ramírez, Guillermo (2006). "Antidepressant and anxiolytic effects of hydroalcoholic extract from Salvia elegans". Journal of Ethnopharmacology. 107 (1): 53–8. doi:10.1016/j.jep.2006.02.003. PMID 16530995.
- Zuardi, A.W.; Crippa, J.A.S.; Hallak, J.E.C.; Moreira, F.A.; Guimarães, F.S. (2006). "Cannabidiol, a Cannabis sativa constituent, as an antipsychotic drug". Brazilian Journal of Medical and Biological Research. 39 (4): 421–9. doi:10.1590/S0100-879X2006000400001. PMID 16612464.
- 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.
- "FDA sends five warning letters over supplements containing picamilon". NutraIngredients-USA.com, William Reed Business Media. 2 December 2015. Retrieved 3 December 2015.
- 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.
- Pierrefiche, G; Zerbib, R; Laborit, H (1993). "Anxiolytic activity of melatonin in mice: Involvement of benzodiazepine receptors". Research communications in chemical pathology and pharmacology. 82 (2): 131–42. PMID 7905658.
- Marseglia, Lucia; D'Angelo, Gabriella; Manti, Sara; Aversa, Salvatore; Arrigo, Teresa; Reiter, Russel; Gitto, Eloisa (2015). "Analgesic, Anxiolytic and Anaesthetic Effects of Melatonin: New Potential Uses in Pediatrics". International Journal of Molecular Sciences. 16 (1): 1209–20. doi:10.3390/ijms16011209. PMC . PMID 25569095.
- Naguib, Mohamed; Gottumukkala, Vijaya; Goldstein, Peter A. (2007). "Melatonin and anesthesia: A clinical perspective". Journal of Pineal Research. 42 (1): 12–21. doi:10.1111/j.1600-079X.2006.00384.x. PMID 17198534.
- Fux M, Levine J, Aviv A, Belmaker RH (1996). "Inositol treatment of obsessive-compulsive disorder". American Journal of Psychiatry. 153 (9): 1219–1221. doi:10.1176/ajp.153.9.1219. 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.
- 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 . PMID 18448634.
- http://pubs.niaaa.nih.gov/publications/aa41.htm[full citation needed]
- 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 . PMID 22003419.
- 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.
- 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.
- CMA & AMA Home medical guides 2012 & 2014, along with personal experiences and WebMD reviews
- Orme-Johnson, David W.; Barnes, Vernon A. (2014). "Effects of the Transcendental Meditation Technique on Trait Anxiety: A Meta-Analysis of Randomized Controlled Trials". The Journal of Alternative and Complementary Medicine. 20 (5): 330–41. doi:10.1089/acm.2013.0204. PMID 24107199.
- Eppley KR, Abrams AI, Shear J (1989). "Differential effects of relaxation techniques on trait anxiety: a meta-analysis". Journal of Clinical Psychology. 45 (6): 957–74. doi:10.1002/1097-4679(198911)45:6<957::aid-jclp2270450622>3.0.co;2-q. PMID 2693491.
- Barnes, Vernon A.; Monto, Andrea; Williams, Jennifer J.; Rigg, John L. (2016). "Impact of Transcendental Meditation on Psychotropic Medication Use Among Active Duty Military Service Members With Anxiety and PTSD". Military Medicine. 181 (1): 56–63. doi:10.7205/MILMED-D-14-00333. PMID 26741477. Lay summary – Neuroscience News (January 11, 2016).