Anxiolytic
An anxiolytic 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.
Nature of anxiety
Anxiety is a naturally occurring emotion and response. 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. Those with anxiety disorders may have concurrent psychological disorders, such as depression. Anxiety disorders are classified using six possible clinical assessments:| Type | Description |
| Generalized anxiety disorders | The anxiety symptoms are usually persistent and constant. Patients of this disorder could experience excessive anxiety for a long duration, commonly over six 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. 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. |
| Post-traumatic stress disorder | PTSDs develop due to experience of severe trauma or life-threatening events. Specific symptoms include flashbacks to traumatic events triggered during similar situations, as well as avoidance of these situations. The fear of re-experiencing the event is also associated with feelings of helplessness or horror. |
| Obsessive–compulsive disorder | 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 obsession. |
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 in the central nervous system. Anti-anxiety medication can be classified into six types according to their different mechanisms: antidepressants, benzodiazepines, azapirones, antiepileptics, antipsychotics, and beta blockers.Antidepressants include selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors. SSRIs are used in all types of anxiety disorders while SNRIs are used for generalized anxiety disorder. 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.
History
The first monoamine oxidase inhibitor, 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.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. 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 were researched and introduced to treat anxiety disorders. The first SSRI, fluoxetine, was discovered in 1974 and approved by FDA in 1987. After that, other SSRIs like sertraline, paroxetine, and escitalopram have entered the market.
The first serotonin norepinephrine reuptake inhibitor, venlafaxine, entered the market in 1993. SNRIs can target serotonin and norepinephrine transporters while avoiding imposing significant effects on other adrenergic, histamine, 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 | 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 | Olanzapine, risperidone |
| Beta-adrenoceptor antagonists | Propranolol, atenolol |
Antidepressants
Medications that are indicated for both anxiety disorders and depression. Selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors are new generations of antidepressants. They have a much lower adverse effect profile than older antidepressants like monoamine oxidase inhibitors and tricyclic antidepressants. Therefore, SSRIs and SNRIs are now the first-line agent in treating long term anxiety disorders, given their applications and significance in all six types of disorders.Benzodiazepines
s 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.
Azapirones
can be useful in GAD but not particularly effective in treating phobias, panic disorder or social anxiety disorders. It is a safer option for long-term use as it does not cause dependence like benzodiazepines.Antiepileptics
Antiepileptics are rarely prescribed as an off-label treatment for anxiety disorders and post-traumatic stress disorders. There have been some suggestions that they may help with anxiety symptoms but there is generally a lack of research on its use.One antiepileptic, pregabalin, has been found to be better at treating GAD than a placebo, and comparable effects to benzodiazepines. It has also been shown be potentially efficient in treating social anxiety disorder. Gabapentin has been prescribed off-label for anxiety despite a lack of research evidence supporting such use, although some studies have indicated that it may relieve anxiety symptoms. The potential anxiolytic effect of tiagabine has been observed in some pre-clinical trials, but its effectiveness has not yet been proved. Similarly, there is a lack of research on valproate for the treatment of anxiety disorders.