What are antianxiety drugs? |

Indications and Procedures

Anxiety disorders are the most common mental health disorders. The fifth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (2013)—the most widely used reference manual for research, clinical assessment, and insurance purposes in the field of psychiatry—lists several anxiety disorders, including generalized anxiety disorder, panic disorder, social anxiety disorder, separation anxiety disorder, agoraphobia, selective mutism, and specific phobias. Anxiety is also a pronounced symptom of other mental illnesses, such as depression, schizophrenia, avoidant personality disorder, dependent personality disorder, post-traumatic stress disorder, and obsessive-compulsive disorder.

Although the physiological responses (sympathetic nervous system activation) and behavioral tendencies (fight-or-flight reaction) are similar, fear and anxiety differ fundamentally in their causes. Anxiety is triggered by the anticipation of a future, life-altering, or adverse event (real or imagined) or the recollection of a past adverse event. Fear is triggered by an encounter with immediate danger. Worrying about an upcoming dentist’s appointment is experienced as anxiety, while facing an armed robber in the hallway is experienced as fear. In both instances, people’s hearts race, their pupils dilate, and their breathing accelerates. The former involves a future orientation, whereas the latter involves a present orientation. Anxiety can be elicited by an excessive concern with “worst-case-scenarios” or irrational thoughts or beliefs about performance or social acceptance. When symptoms of anxiety become distressful and cause impairment in functioning (for example, the inability to work or attend school), then diagnosis of an anxiety disorder and the use of antianxiety medications and other therapeutic interventions are indicated.

Uses and Complications

The first line of treatment for anxiety disorders is cognitive behavioral therapy, which has been shown to be as effective as medications in the treatment of anxiety. In cases where psychotherapy alone is insufficient to treat the anxiety, antianxiety medications may be prescribed to help control symptoms. Three major categories of antianxiety medications, also known as anxiolytics, are used to treat anxiety disorders, and each of these act on similar neural transmitters and pathways: benzodiazepines, selective serotonin reuptake inhibitors (SSRIs), and selective norepinephrine reuptake inhibitors (SNRIs). Tricyclic antidepressants are also used in the treatment of anxiety disorders, although SSRIs are preferred due to their greater safety and tolerability. Barbituates, which act as central nervous system depressants, were once the first line of treatment for anxiety disorders, but their clinical use in the treatment of anxiety has been phased out due to the high risk of overdose and dependence.

Selective serotonin reuptake inhibitors. Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed medications for the treatment of anxiety. As their name suggests, SSRIs act by increasing the levels of serotonin (5-hydroxytryptamine) in the brain by preventing its reuptake by neurons. When first approved for use, SSRIs were widely acclaimed as breakthrough medications in the treatment of depression, and clinical practice soon demonstrated their effectiveness in alleviating the symptoms of anxiety as well. Medications in this class include fluoxetine (Prozac), sertraline (Zoloft), fluvoxamine (Luvox), paroxetine (Paxil), citalopram (Celexa), and escitalopram (Lexapro).

SSRIs require four to six weeks to reach maximum efficacy and can cause withdrawal symptoms if their use is stopped abruptly. The ingestion of large doses of SSRIs can result in severe toxicity, but fatal overdoses are rare. Hence, the risk of lethality from excessive SSRI use is minimal, especially when compared to other anxiolytics. In addition, SSRIs are nonaddictive and do not cause memory impairment. However, the list of potential side effects associated with SSRI use is lengthy: anhedonia, photosensitivity, drowsiness, headache, bruxism, vivid and bizarre dreams, dizziness, fatigue, urinary retention, changes in appetite, weight gain, suicidal ideation, tremors, orthostatic hypotension, and increased sweating. In addition, the sexual side effects that stem from SSRI use include reduced libido, erectile dysfunction, anorgasmia, genital anesthesia, and premature ejaculation.

Serotonin norepinephrine reuptake inhibitors. Serotonin norepinephrine reuptake inhibitors (SNRIs) work by blocking the reuptake of serotonin and norepinephrine in the brain. Various SNRIs block the reuptake of these neurotransmitters with differing affinity ratios, so that an SNRI that causes uncomfortable side effects in a patient may be replaced with another that does not have the same negative effects. The most common side effect of SNRIs is nausea, followed by dry mouth, sweating, constipation, and heart palpitations. Medications in this class include venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq).

Benzodiazepines. The first benzodiazepine, chlordiazepoxide (Librium), was discovered in 1955. Benzodiazepines enhance the effects of gamma-aminobutyric acid (GABA), which is the chief inhibitory neurotransmitter in the central nervous system, making them useful in the treatment of anxiety. Benzodiazepines are fast-acting and typically relieve symptoms within thirty to sixty minutes of ingestion. Although cognitive impairment and paradoxical effects such as aggression, agitation, mania, or suicidality can occasionally occur with benzodiazepine use, these drugs are generally safe and effective in the short term. Benzodiazepines possess sedative and hypnotic properties that are useful in treating agitation and insomnia. Most benzodiazepines are administered orally; however, they can also be given intravenously, intramuscularly, or rectally. Other benzodiazepines are alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), lorazepam (Ativan), and oxazepam (Serax).

Benzodiazepines can cause many side effects, including blurred or double vision, slowed reflexes, impaired thinking and judgment, dizziness, slurred speech, and depression. These effects are especially evident with prolonged use and at higher dosages, which can lead to abuse and dependence. The fastest-acting benzodiazepines (for example, Xanax) have the greatest potential for addiction and are listed as Schedule IV controlled substances. A sudden decrease in the dosage or abrupt cessation of benzodiazepine use can result in symptoms of rebound, which is a return of anxiety but at intensities that are higher than initial levels, and of withdrawal, which causes insomnia, sweating, shaking, confusion, and tachycardia (elevated heart rate). Hence, a gradual reduction in the dosage and administration of these medications is recommended.

Tricyclic antidepressants. Antidepressants are also used in the treatment of anxiety. The first class of antidepressants prescribed as anxiolytics are known as tricyclic antidepressants (TCAs), which are named for the chemical structure of the drugs in the class—three rings. The first TCA, imipramine (Tofranil), was discovered in the late 1950s. Other examples of tricyclic antidepressants are amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil). The side effects of TCAs include hypotension (low blood pressure), blurry vision, dizziness, constipation, dry mouth, drowsiness, increased appetite, and weight gain. In addition, an overdose of TCAs can often be fatal. The severe morbidity and mortality associated with these drugs is well documented because of their cardiovascular and neurological toxicity. Due to their greater safety and tolerability, SSRIs are the preferred treatment for anxiety.

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