Anxiolytic
An anxiolytic (/ˌæŋksiəˈlɪtɪk, ˌæŋksioʊ-/; also antipanic or anti-anxiety agent)[1] 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.
Anxiolytic
Etiology[edit]
The etiology of anxiety disorder remains unknown. There are several contributing factors that are still yet to be proved to cause anxiety disorders.[2] These factors include childhood anxiety, drug induction by central stimulant drugs, metabolic diseases or having depressive disorder.
Medications[edit]
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.[3] Anti-anxiety medication can be classified into six types according to their different mechanisms: antidepressants, benzodiazepines, azapirones, antiepileptics, antipsychotics, and beta blockers.[3][4]
Antidepressants include 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.[4] Buspirone is indicated for GAD, which has much slower onset but with the advantage of less sedating and withdrawal effects.[5]
History[edit]
The first monoamine oxidase inhibitor (MAOI), iproniazid, was discovered accidentally when developing the new antitubercular drug isoniazid. The drug was found to induce euphoria and improve the patient's appetite and sleep quality.[6]
The first tricyclic antidepressant, imipramine, was originally developed and studied to be an antihistamine alongside other first-generation antihistamines of the time, such as promethazine.[7] TCAs can increase the level of norepinephrine and serotonin by inhibiting their reuptake transport proteins.[8] 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) were researched and introduced to treat anxiety disorders. The first SSRI, fluoxetine (Prozac), was discovered in 1974 and approved by FDA in 1987. After that, other SSRIs like sertraline (Zoloft), paroxetine (Paxil), and escitalopram (Lexapro) have entered the market.[7]
The first serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine (Effexor), entered the market in 1993.[7] SNRIs can target serotonin and norepinephrine transporters while avoiding imposing significant effects on other adrenergic (α1, α2, and β), histamine (H1), muscarinic, dopamine, or postsynaptic serotonin receptors.
Mechanism of action[edit]
SSRIs and SNRIs[edit]
Both selective serotonin reuptake inhibitors (SSRI) and serotonin and norepinephrine reuptake inhibitors (SNRI) 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.[9] 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.[2][9]
Benzodiazepine[edit]
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.[9]
Clinical use[edit]
Selective serotonin reuptake inhibitors[edit]
Selective serotonin reuptake inhibitors (SSRIs) are a class of medications used in the treatment of depression, anxiety disorders, OCD and some personality disorders.[14][15] SSRIs are the first-line anti-anxiety medications.[16] Serotonin is one of the crucial neurotransmitters in mood enhancement, and increasing serotonin level produces an anti-anxiety effect.[17] 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.[16]
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.[13]
Alternatives to medication[edit]
Cognitive behavioral therapy (CBT) is an effective treatment for panic disorder, social anxiety disorder, generalized anxiety disorder, and obsessive–compulsive disorder, while exposure therapy is the recommended treatment for anxiety related phobias. Healthcare providers can guide those with anxiety disorder by referring them to self-help resources.[61] Sometimes medication is combined with psychotherapy but research has not found a benefit of combined pharmacotherapy and psychotherapy versus monotherapy.[62]
If CBT is found ineffective, both the Canadian and American medical associations then suggest the use of medication.[63]
