anxiolytic anxiolytic an anxiolytic (/ˌæŋksiəˈlɪtɪk, ˌæŋksioʊ-/; also antipanic or anti-anxiety agent) 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 disorders and their related psychological and physical symptoms. anxiolyticdrug classclass identifierssynonymssedative, minor tranquilizeruseanxiety disordersclinical datadrugs.comdrug classesin wikidata nature of anxiety anxiety is a naturally-occurring emotion and an innate response of the body to the environmental stimuli. mild to moderate anxiety would increase level of performance. however, when anxiety levels exceed the tolerability of a person, anxiety disorders may occur. people with anxiety disorders can exhibit fear responses such as defensive behaviors, high levels of alertness and negative emotions, without external stimuli which induce anxiety within an individual. those with anxiety disorders are also often found to have concurrent psychological disorders, most commonly depression. anxiety disorders are divided into 6 types in clinical recognition. they are as follows. type description generalized anxiety disorders (gad) the anxiety symptoms are usually persistent and constant. patients of this disorder could experience excessive anxiety for a long duration, commonly over 6 months and the symptoms could occur without any specific triggers. panic disorder this disorder specifically refers to the suffering from panic attacks and also the fear of repetitive attacks. commonly found in agoraphobia patients (the fear of difficulty in leaving a confined venue). panic attacks are sudden upsurges in anxiety level usually with unexplained reasons. social phobia this refers to the fear of staging in social situations where one experiences public observation among people or performs in front of the public. the fears are often unexplained and persistent. the fear could also be attributed to the possible humiliation in front of others due to poor performance or awkward social interactions. specific phobias persistent fear towards a specific object, either tangible or intangible. this leads to undeniable avoidance or thought of escape from the object or endurance of the object in immense levels of anxiety. posttraumatic stress disorder (ptsd) ptsds develop due to experience of severe trauma or life-threatening events. specific symptoms include flashbacks of the traumatic events during the encounter to the similar situations and avoidance of these situations. the fear of re-experiencing the event are also associated with feelings of helplessness or horror. obsessive-compulsive disorder (ocd) person with ocd would experience compulsive impulses of removing an obsession. one common example is the obsession with impurities or contamination. the person would have compulsion or urge in sterilizing the environment to remove the contamination. another example is the obsession with orderliness. the person would manipulate the surroundings including visual presentations to ease their compulsion. different types of anxiety disorders will share some general symptoms while having their own distinctive symptoms. this explains why people with different types of anxiety disorders will respond differently to different classes of anti-anxiety medications. etiology the etiology of anxiety disorder remains unknown. there are several contributing factors that are still yet to be proved to cause anxiety disorders. these factors include childhood anxiety, drug induction by central stimulant drugs, metabolic diseases or having depressive disorder. medications anti-anxiety medication is any drug that can be taken or prescribed for the treatment of anxiety disorders, which may be mediated by neurotransmitters like norepinephrine, serotonin, dopamine, and gamma-aminobutyric acid (gaba) in the central nervous system. anti-anxiety medication can be classified into six types according to their different mechanisms: antidepressants, benzodiazepines, buspirone, antiepileptics, antipsychotics, and beta blockers. antidepressants including selective serotonin reuptake inhibitors (ssris), serotonin-norepinephrine reuptake inhibitors (snris), tricyclic antidepressants (tca), monoamine oxidase inhibitor (maoi). ssris are used in all types of anxiety disorders while snris are used for generalized anxiety disorder (gad). both of them are considered as first-line anti-anxiety medications. tcas are second-line treatment as they cause more significant adverse effects when compared to the first-line treatment. benzodiazepines are effective in emergent and short-term treatment of anxiety disorders due to their fast onset but carry the risk of dependence. buspirone is indicated for gad, which has much slower onset but with the advantage of less sedating and withdrawal effects. anti-anxiety medications may cause adverse reactions, addiction, and withdrawal symptoms. history the first monoamine oxidase inhibitor (maoi), iproniazid, was discovered accidentally when developing the new antitubercular drug isoniazid. the drug was found to cause euphoria and improve the patient's appetite and sleep quality. the first tricyclic antidepressant, imipramineis, was developed by modifying the structure of antihistamine (promethazine). tcas can increase the level of norepinephrine and serotonin by inhibiting their reuptake transport proteins. the majority of tcas exert greater effect on norepinephrine, which leads to side effects like drowsiness and memory loss. in order to be more effective on serotonin agonism and avoid anticholinergic and antihistaminergic side effects, selective serotonin reuptake inhibitors (ssri) to treat anxiety disorder. first ssri, fluoxetine, was reported in 1974 and approved by fda in 1987. after that, few more ssri like sertraline, paroxetine, escitalopram have entered the market. the first serotonin norepinephrine reuptake inhibitor (snri), venlafaxine, entered the market in 1993. snris can target serotonin and norepinephrine transporters while imposing insignificant effect on other adrenergic (α1, α2, and β), histamine (h1), muscarinic, dopamine, or postsynaptic serotonin receptors. classifications there are six groups of anti-anxiety medications available that have been proven to be clinically significant in treatment of anxiety disorders. the groups of medications are as follows. drug class examples antidepressants (e.g.ssris, snris) ssris e.g. fluoxetine, sertraline; snris e.g. venlafaxine; maois; tcas benzodiazepines lorazepam, diazepam, alprazolam azapirones buspirone, gepirone, tandospirone antiepileptics gabapentin, pregabalin, tiagabine and valproate antipsychotics olanzepine, risperidone beta-adrenoceptor antagonists propranolol antidepressants medications that are indicated for both anxiety disorders and depression. selective serotonin reuptake inhibitors (ssris) and serotonin-norepinephrine reuptake inhibitors (snris) are new generations of antidepressants. they have a much lower adverse effect profile than older antidepressants like monoamine oxidase inhibitors (maois) and tricyclic antidepressant (tcas). therefore, ssris and snris are now the first-line agent in treating long term anxiety disorders, given their applications and significance in all 6 types of disorders. benzodiazepines benzodiazepines are used for acute anxiety and could be added along with current use of ssris to stabilize a treatment. long-term use in treatment plans is not recommended. different kinds of benzodiazepine will vary in its pharmacological profile, including its strength of effect and time taken for metabolism. the choice of the benzodiazepine will depend on the corresponding profiles. benzodiazepines are used for emergent or short-term management. they are not recommended as the first-line anti-anxiety drugs, but they can be used in combination with ssris/snris during the initial treatment stage. indications include panic disorder, sleep disorders, seizures, acute behavioral disturbance, muscle spasm and premedication and sedation for procedures. buspirone useful in gad but not effective in treating phobias or social anxiety disorders. antiepileptics useful in treating gad antipsychotics olanzapine and risperidone are atypical antipsychotics which are also effective in gad and ptsd treatment. however, there is a higher chance of experiencing adverse effects than the other anti-anxiety medications. beta-adrenoceptor antagonists propranolol is originally used for heart diseases. it can also be used to treat anxiety with symptoms like tremor or increased heart rate. they work on the nervous system and alleviate the symptoms as a relief. mechanism of action selective serotonin reuptake inhibitors (ssri) and serotonin and norepinephrine reuptake inhibitors (snri) both ssris and snris are reuptake inhibitors of a class of nerve signal transduction chemical called neurotransmitters. serotonin and norepinephrine are neurotransmitters that are related to nervous control in mood regulation. the level of neurotransmitters are regulated by the nerve through reuptake to avoid accumulation of the neurotransmitter at the endings of nerve fiber. by reuptaking the produced neurotransmitter, the level will go back down and ready to go back up upon excitation from a new nerve signal. however the level of patients with anxiety disorders are usually low or their nerve fibers are insensitive to the neurotransmitters. ssris and snris will then block the channel of reuptake and increase the level of the neurotransmitter. the nerve fibers will originally inhibit further production of neurotransmitters upon the increase. however the prolonged increase will eventually desensitize the nerve about the change in level. therefore, the action of both ssris and snris will take 4–6 weeks to exert their full effect. benzodiazepine benzodiazepines bind selectively to the gaba receptor, which is the receptor protein found in the nervous system and is in control of the nervous response. benzodiazepine will increase the entry of chloride ions into the cells by improving the binding between gaba and gaba receptors and then the better opening of the channel for chloride ion passage. the high level of chloride ion inside the nerve cells makes the nerve more difficult to depolarize and inhibit further nerve signal transduction. the excitability of the nerves then reduces and the nervous system slows down. therefore, the drug can alleviate symptoms of anxiety disorder and make the person less nervous. clinical use 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. ssris are the first-line anti-anxiety medications. serotonin is one of the crucial neurotransmitters in mood enhancement, and increasing serotonin level produces an anti-anxiety effect. ssris increase the serotonin level in the brain by inhibiting serotonin uptake pumps on serotonergic systems, without interactions with other receptors and ion channels. ssris are beneficial in both acute response and long-term maintenance treatment for both depression and anxiety disorder. 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. the ssris paroxetine and escitalopram are usfda approved to treat generalized anxiety disorder. therapeutic use drug indication common side effect citalopram -depressive illness -panic disorder -acute angle closure glaucoma -apathy (caused by decrease in dopamine release) -flatulence -drowsiness -hypersalivation -migraine -rhinitis escitalopram (active enantiomer of citalopram) -depressive illness -generalized anxiety disorder -obsessive-compulsive disorder -panic disorder -social anxiety disorder -sinusitis fluoxetine -major depression -bulimia nervosa -obsessive-compulsive disorder -menopausal symptoms -chills -feeling abnormal -postmenopausal hemorrhage -uterine disorder -vasodilation -vision blurred adverse effect the common early side effects of ssris include nausea and loose stool, which can be solved by discontinuing the treatment. headache, dizziness, insomnia are the common early side effects as well. sexual dysfunction, anorgasmia, erectile dysfunction, and reduced libido are common adverse side effects of ssris. sometimes they may persist after the cessation of treatment. withdrawal symptoms like dizziness, headache and flu-like symptoms (fatigue/myalgia/loose stool) may occur if ssri is stopped suddenly. the brain is incapable of upregulating the receptors to sufficient levels especially after discontinuation of the drugs with short half life like paroxetine. both fluoxetine and its active metabolite have a long half life therefore it causes the least withdrawal symptoms. 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. 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 different adverse effects. examples include imipramine, doxepin, amitriptyline, nortriptyline and desipramine. therapeutic use drugs indication common side effect imipramine -nocturnal enuresis for children above six years old -severe depression -antihistamine side effects like sedation, weight gain -anticholinergic side effect like blurred vision, dry mouth, constipation clomipramine -depressive illness -phobic and obsessional states -adjunctive treatment of cataplexy associated with narcolepsy -aggression -anxiety -arrhythmias -breast enlargement contraindication tcas may cause drug poisoning in patients with hypotension, cardiovascular diseases and arrhythmias. tetracyclic antidepressants 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. 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