How do Anxiolytic Medications Work?
Antidepressants have become the mainstay treatment for most types of anxiety due to their efficacy, tolerability, and safety when compared to other drug classes. Antidepressants are the drug of choice in people who are diagnosed with depression and anxiety. It takes an average of 4 weeks to see the effects of antidepressants.
Serotonin and norepinephrine are two of the main neurotransmitters that contribute to activating stress-adapting pathways and feelings of happiness. Since certain antidepressants modulate levels of these neurotransmitters, they are also effective in treating anxiety.
Selective serotonin reuptake inhibitors (SSRIs) – SSRIs work by blocking the reuptake of serotonin by nerves. This leads to a higher concentration of serotonin. They are regarded by most practitioners as first line medications for treating anxiety.
Serotonin-norepinephrine reuptake inhibitors (SNRIs) – SNRIs work similarly to SSRIs except in addition to serotonin, they also inhibit the reuptake of norepinephrine.
Tricyclic antidepressants (TCAs) – TCAs have a different structure, but like SNRIs, they also block the reuptake of serotonin and norepinephrine. TCAs also have a little effect on dopamine as well.
Benzodiazepines work by binding to gamma-aminobutyric acid (GABA) receptors. Activation of GABA receptors slows down communication between neurons. Therefore, benzodiazepines reduce anxiety by decreasing brain activity. Benzodiazepines work relatively faster than antidepressants. This is why they are used for quick symptom relief.
The long-term use of benzodiazepines for treating anxiety has declined because they cause dependency, withdrawal symptoms, and may be abused. There is also some variability within the class of benzodiazepines. Alprazolam and diazepam may be preferred for immediate relief of anxiety because they have a faster onset.
Lorazepam, oxazepam, and temazepam are preferred for elderly patients because they are they are converted to inactive forms in the body.
Buspirone’s activity is not fully understood but it works by acting on serotonin receptors in the brain (specifically 5-HT1A), thus reducing firing of neurons and excitation which may help ease anxiety. It does not cause dependence. However, buspirone may take 2-4 weeks before any benefits are seen. It is used for augmenting other treatments and is typically used as a second or third-line agent.
Pregabalin is a GABA analog, however, its mechanism of action is not well understood. Pregabalin is not approved by the FDA for the treatment of anxiety disorder and it is usually used when other first-line agents have failed.
Hydroxyzine is an antihistamine that binds to histamine H1 receptors. It is a second line agent for treating anxiety. Hydroxyzine causes sedation and is useful for treating insomnia associated with anxiety.