Anxiolytic

An anxiolytic (also antipanic or antianxiety agent)[1] 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/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 and its related psychological and physical symptoms. Anxiolytics have been shown to be useful in the treatment of anxiety disorders. Light therapy and other interventions have also been found to have an anxiolytic effect.[2]

Beta-receptor blockers such as propranolol and oxprenolol, although not anxiolytics, can be used to combat the somatic symptoms of anxiety, as tachycardia and palpitations.[3]

Anxiolytics are also known as minor tranquilizers.[4] The term is less common in modern texts, and was originally derived from a dichotomy with major tranquilizers, also known as neuroleptics or antipsychotics.

Alternatives to medication

Psychotherapeutic treatment can be an effective alternative to medication.[5] 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.[6] 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.[7] Sometimes medication is combined with psychotherapy, but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.[8]

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.[9]

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"[10] 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)" [11]

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.[12]

Medications

Barbiturates

Main article: Barbiturate

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

Main article: Benzodiazepine

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. If benzodiazepines are discontinued rapidly after being taken daily for two or more weeks there is a risk of benzodiazepine withdrawal and rebound syndrome, and tolerance and dependence may also occur, but may be clinically acceptable.[13] There is also the added problem of the accumulation of drug metabolites and adverse effects.[14] Benzodiazepines include:

Benzodiazepines exert their anxiolytic properties at moderate dosage. At higher dosage hypnotic properties occur.[15]

Antidepressants

Serotonergic antidepressants

Selective serotonin reuptake inhibitors or serotonin-specific reuptake inhibitor[16] (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; nevertheless, most SSRIs have anxiolytic properties. They can, however, be anxiogenic early on in the course of treatment due to negative feedback through the serotonergic autoreceptors. For this reason in some individuals a low dose concurrent benzodiazepine therapy might be beneficial during the early stages of serotonergic therapy to counteract the initial anxiogenic effects current serotonergics antidepressants have.

Serotonin–norepinephrine reuptake inhibitor

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.[17]

Tricyclic antidepressant

Older tricyclic antidepressants (TCAs) are anxiolytic too; however, their side effects are often more severe in nature. Examples include imipramine, doxepin, amitriptyline, and the unrelated trazodone.

Tetracyclic antidepressant

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, it in many countries (such as USA and Australia) it is not specifically approved for anxiety disorders and is only used off label.

Monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs) are very effective for anxiety, but due to drug dangers, are rarely prescribed. Examples include: phenelzine, isocarboxazid and tranylcypromine. A reversible MAOI, which has none of the dietary restrictions associated with classic MAOI's, moclobemide is used in Canada and the UK as ′Manerix′ and in Australia as ′Aurorix′ which have none of the more severe SSRI's and SNRI's caused SSRI discontinuation syndrome, an often overlooked and damaging syndrome which is objectively and subjectively as bad or, for some, even worse than Benzodiazepine withdrawal syndrome.

Beta blockers

Although not officially approved for this purpose, Beta blockers also can have an antianxiety effect.[18][19]

Miscellaneous

Alpha-adrenergic agonist

Alpha 2A receptor agonists Clonidine and Guanfacine has demonstrated both anxiolytic and anxiogenic effects.

Mebicar

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.[20] Mebicar decreases the brain noradrenaline level, exerts no effect on the dopaminergic systems, and increases the brain serotonin level.[21]

Fabomotizole

Fabomotizole[22] (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 antagonism, MT3 receptor antagonism, and sigma agonism all thought to have some involvement.[23][24][25][26][27] It has yet to find clinical use outside of Russia.

Selank

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.

Bromantane

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.

Emoxypine

Emoxypine is an antioxidant that is also an anxiolytic. Its chemical structure resembles that of pyridoxine, a type of vitamin B6.

Azapirones

Azapirones are a class of 5-HT1A receptor agonists. Currently approved azapirones include buspirone (Buspar) and tandospirone (Sediel).

Hydroxyzine

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.[28] It has been shown to be as effective as benzodiazepines in the treatment of generalized anxiety disorder, while producing fewer side-effects.[29]

Pregabalin

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.[30][31]

Menthyl isovalerate

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.[32][33][34]

Cannabidiol

Cannabidiol (CBD) is a cannabinoid produced by Cannabis sativa and Cannabis indica, and in marginal quantities by Cannabis ruderalis. It is available in the United States in states where cannabis has been legalized for medical and general use. No lethal dose (or LD50) has been established from cannabidiol . In feral strains of cannabis, cannabidiol is produced in large quantities alongside the psychoactive cannabinoid tetrahydrocannabinol. Special strains of cannabis have been bred to yield high amounts of cannabidiol with significantly lowered synthesis of THC. Specific formulations for anxiety with a CBD to THC ratio of 18:1 are available in the US markets .

Tetrahydrocannabinol

Tetrahydrocannabinol appears to be capable of both, having anxiolytic effect(s) and having anxiogenic effect(s).

Racetams

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

Herbal treatments

Certain natural substances are reputed to have anxiolytic properties, including the following:

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.[41][42] Picamilon is sold in the United States as a dietary supplement, while in Russia it is sold as a prescription drug.

Chlorpheniramine (Chlor-Trimeton)[43] 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 mediated by the benzodiazepine/GABAergic system.[44] It has been used experimentally as an effective premedicant for general anesthesia in surgical procedures.[45]

Inositol:[46] 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.[47]

Future drugs

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:

Common drugs

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).

Alcohol

Ethanol is used as an anxiolytic, sometimes by self-medication. fMRI can measure the anxiolytic effects of alcohol in the human brain.[48] 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.[49]

Inhalants

The anxiolytic effects of solvents act as positive modulators of GABAA receptors (Bowen and colleagues 2006).[50]

See also

References

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  2. ↑ 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.
  3. ↑ Peggy E. Hayes; et al. (September–October 1987). "Beta-blockers in anxiety disorders". Journal of Affective Disorders 13 (2): 119–130. doi:10.1016/0165-0327(87)90017-6.
  4. ↑ "anxiolytic (tranquilizer)". Memidex (WordNet) Dictionary/Thesaurus. Retrieved 2010-12-02.
  5. ↑ 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.
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  7. ↑ 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.
  8. ↑ 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.
  9. ↑ CMA & AMA Home medical guides 2012 & 2014, along with personal experiences and WebMD reviews
  10. ↑ David W. Orme-Johnson, Vernon A. Barnes (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): 330–341. doi:10.1089/acm.2013.0204.
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  12. ↑ PTSD Symptoms May Be Reduced With Transcendental Meditation - Neuroscience News January 11, 2016
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