anxiolytics Photo courtesy of HealthlineOpens in new window

Anxiolytics are medications used to reduce tension, relieve anxiety or irritability, and treat insomnia.

Medications used in the treatment of anxiety disorders include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), high-potency benzodiazepines (e.g., Valium), monoamine oxidase inhibitors (MAOIs), other agents (e.g., barbiturates, meprobamate, sedative-hypnotics, antihistamines, and buspirone), and combination treatments (Patterson, 2006; Preston, O’Neal, & Talaga, 2008).

Humans (and other animals) have adaptive survival mechanisms that cause them to experience fear, which can help them avoid harmful situations. For example, when confronted with a threat (e.g., coming across a rattlesnake), the body may react with increased heart rate, sweating, and other fight-or-flight responses. This adrenaline responses may increase one’s ability to escape a dangerous situation.

The ability to learn what situations may be dangerous, allows individuals to avoid these situations in the future. However, when fear is out of proportion to actual threat (e.g., reacting with fear to any mention of snakes), anxiety may ensue.

Avoidance learning consists of conditioned fear (an immediate response, including freezing behavior, a feeling of fear, or other reactions), which involves the brain’s amygdale, followed by an avoidance response (i.e., movement such as running away), which involves other brain structures, including the basal ganglia, frontal cortex, and hippocampus (LeDoux, 1996).

BenzodiazepinesOpens in new window enhance the effects of the neurotransmitter gamma-aminobutyric acid (GABA), an inhibitory chemical messenger that helps regulate excitability, ameliorating the conditioned fear response (LeDoux, 1996). Other anxiolytics influence the neurotransmitters serotonin and norepinephrine, which are also involved in anxietyOpens in new window (Patterson, 2006).

The first benzodiazepine—chlordiazepoxide (Librium)—was developed in 1957. Benzodiazepines were a significant improvement over previous anxiety medications, which included barbiturates, meprobamate (Miltown), tybamate (Solacen, Tybattam), glutethimide (Doriden), methyprylon (Noludar), and ethchlorvynol (Placidyl; Preston et al., 2008).

Many of these earlier tranquilizers have high abuse potential; they can cause tolerance and severe withdrawal symptoms. The late Chief Justice William Rehnquist used Placidyl for insomnia and back pain from 1972 through 1981, when he was hospitalized for his back pain. He experienced severe withdrawal, including delusions, and had to be tapered off the drug over a period of several months (Mauro, 2007).

Benzodiazepines have both sedative and hypnotic properties. Medications with sedative properties are used to treat anxiety; hypnotics are used in the treatment of insomnia (to induce or maintain sleep). Benzodiazepines are also used as anesthetics or to aid in withdrawal from other drugs; they are fast acting and effective against anxiety. Side effects may include sedation, slurred speech, lack of coordination, and lessening of inhibitions.

Some benzodiazepines (triazolam, midazolam, and lorazepam) can cause anterograde amnesiaOpens in new window, resulting in memory loss for a period of time after the drug has worn off (Preston et al., 2008). Different benzodiazepines have varying degrees of abuse potential, physiological dependence, and withdrawal symptoms. It can be dangerous to combine benzodiazepines with alcohol; this combination is what caused Karen Ann Quinlan’s comaOpens in new window (Preston et al., 2008).

Because many people have anxiety or insomnia, benzodiazepines have been widely used. Valium, which was introduced in 1963, became one of the best-selling pharmaceutical drugs on the marker, reaching peak sales in the United States in 1978 (Bakalar, 2005).

In addition to Valium and Librium, some of the better known benzodiazepines include Xanax, Klonopin, Rohypnol, Dalmane, lorazepam (Ativan), midazolam (Versed), Restoril, and Halcion. Some of the newer atypical benzodiazepines (e.g., ProSom, quazepam) and nonbenzodiazepines (e.g., Ambien, Lunesta, Sonata) are used as hypnotics; they may be associated with less cognitive impairment, daytime fatigue, and a reduced risk of dependency (Preston et al., 2008). Benzodiazepines should not be used during pregnancy or while nursing (Preston et al., 2008).

Buspirone (BuSpar)Opens in new window a partial serotonin receptor (HT-1A) agonist, has anxiolytic effects and is also used as an augmentative treatment for depression. It has low potential for dependence or tolerance and fewer side effects than benzodiazepines; side effects include nausea, dizziness, and anxiety.

A disadvantage of buspirone is its delayed onset of action—between one and two weeks before therapeutic benefits are experienced. It is not effective for everyone, especially people who have previously used benzodiazepines.

Some antihistamines (e.g., hydroxyzine, Benadryl) are used to treat anxiety. They cause sedation (and reduce anxiety) by blocking histamine receptors in the central nervous system. They work quickly (within 30 minutes) and last four to six hours. They are not habit forming, but they can cause drowsiness, which can make it difficult to gauge the correct therapeutic dose that will reduce anxiety without causing sedation (Preston et al., 2008).

Beta blockers and clonidine are typically used to treat high blood pressure but are also effective in the treatment of some anxiety disorders. Beta blockers (e.g., atenolol, Indreral) act by blocking the effects of norepinephrine: they reduce the physical manifestations of anxiety (sweating, increased heart rate, tremor). Thus they are more effective in treating periodic anxiety, such as performance anxiety, than ongoing social or generalized anxiety disorder.

Side effects of beta blockers can include dizziness, low blood pressure, and depression. Clonidine (Catapres) is an alpha-2 adrenergic agonist that inhibits the release of norepinephrine. In addition to anxiety, it is also used to treat opiate withdrawal. Tiagabine (Gabitril) is a selective GABA reuptake inhibitor used as an anticonvulsant and to treat anxiety.

Research has explored tiagabine’s effectiveness in the treatment of panic disorder and posttraumatic stress disorder, but more research is needed to demonstrate its efficacy (Preston et al., 2008).

Some of the antidepressants are used in the treatment of anxiety. Examples include the TCA opipramol (Neuraxpharm, Insidon); the MAOI phenelzine (Nardil); SSRIs Lexapro, Luvox, Paxil, and Zoloft; serotonin-norepinephrine reuptake inhibitors (SNRI) nefazodone (Serzone) and venlafaxine (Effexor); the reversible inhibitor of monoamine oxidase A (RIMA) brofaromine (Consonat); and noradrenergic and specific serotonergic antidepressant (NaSSA) mirtazapine (Remeron).

See also:
  1. LeDoux, J. (1996). The emotional brain: The mysterious underpinnings of emotional life. New York: Touchstone.
  2. Preston, J.D., O’Neal, J. H., & Talaga, M.C. (2008). Handbook of clinical psychopharmacology for therapists (5th ed.). Oakland, CA: New Harbinger.