Anxiolytics

Definition

Anxiolytics are prescription drugs used to treat and prevent anxiety disorders. Anxiety is an emotional state in which fear dominates a person's life. Drugs that are often prescribed to manage anxiety episodes are known as benzodiazepines . Probably the best-known example of a benzodiazepine is the anxiolytic diazepam . In the United States, diazepam is sold under the brand name Valium.

All together, there are six other anxiolytics approved for use in the United States. All of these medications are similar to diazepam in their chemical structures and the way they exert their beneficial anxiolytic effects. However, these drugs differ from one another in several important ways. Some drugs work faster than others, while other drugs continue their anxiolytic effects for longer periods of time. Additionally, some anxiolytics differ from one another in the way that they are eliminated from the body, and others are involved with more drug-to-drug interactions than others. In 2002, the two most commonly prescribed anxiolytics were the drugs lorazepam, sold under the trade name of Ativan, and alprazolam, sold under the brand name of Xanax.

Purpose

Diazepam and other anxiolytics reduce the frequency, severity, and duration of anxiety symptoms in individuals who have medical or psychiatric disorders associated with anxiety. Illnesses associated with anxiety symptoms include heart disease, gastrointestinal diseases, as well as diseases that affect the lungs and make breathing difficult. Anxiety may also occur in the absence of these diseases and is thought to involve abnormal function of several different neurotransmitters in a region of the brain known as the amygdala. The amygdala plays a critical role in assessing fear and responding to danger. Examples of common anxiety disorders include generalized anxiety disorder, panic disorder, and phobic disorders. Nearly 25% of the population will develop an anxiety disorder at some time during their life.

Description

Benzodiazepine anxiolytics like diazepam have similar chemical structures, including a benzene ring fused to a diazepine ring. This structure is important for anxiolytic activity. In the brain, anxiolytics are believed to enhance the actions of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter. By enhancing GABA's inhibitory actions, brain cells are unable to be stimulated by excitatory neurotransmitters, and this inhibition alleviates symptoms of anxiety.

Although benzodiazepines like diazepam alleviate symptoms of anxiety in a manner similar to older anxiolytics like barbiturates, the distinctive feature that sets benzodiazepines apart from barbiturates is the wide margin of safety associated with benzodiazepines. Unlike barbiturates, benzodiazepine anxiolytics have a wide margin of safety, meaning that the doses of benzodiazepines that cause life-threatening toxicities are considerably larger than the doses that are normally used for alleviating anxiety.

Diazepam and related anxiolytics are safe and effective medications for alleviating anxiety symptoms. Until the 1990s, these drugs were the mainstay of pharmacologic treatment for anxiety-related disorders. However, these anxiolytics do possess some unwanted properties. For example, the Drug Enforcement Administration (DEA) classifies diazepam and related anxiolytics as controlled substances because the drugs are sometimes abused, or used for recreational purposes due to their desirable anxiolytic effects. Additionally, physical dependence develops when these medications are used at high doses or for prolonged periods of time. This means that people experience unpleasant withdrawal symptoms if they abruptly stop taking their medication. Common withdrawal symptoms include anxiety, insomnia, restlessness, agitation, muscle tension, and irritability, although seizures and depression may sometimes occur. The unpleasant withdrawal effects that are experienced when discontinuing these medications cause people to continue using the drugs to avoid unpleasant effects. Because these drugs are sometimes used for non-medicinal purposes and are associated with unpleasant withdrawal symptoms, benzodiazepine anxiolytics are now typically prescribed only for short-term treatment of anxiety disorders, until other anxiolytics like buspirone or selective serotonin reuptake inhibitors (SSRIs) begin working.

Recommended dosage

The usual adult dosage of diazepam is 2–10 mg taken by mouth two to four times a day. In addition to oral tablets, diazepam is also available as an oral liquid or as an injection that can be given either intramuscularly or intravenously to individuals with severe anxiety symptoms.

Dosages for anxiolytics that are chemically related to diazepam vary. Examples include alprazolam given by mouth in dosages of 0.25–0.5 mg three times a day, or lorazepam taken by mouth in dosages of 0.5–2 mg two or three times a day.

The anxiolytic effects of diazepam occur in as little as 15 minutes, but only last for two or three hours. These features make diazepam an ideal drug for quickly eliminating acute anxiety attacks. On the other hand, lorazepam's anxiolytic effects are a little slower in onset but tend to persist for more than six hours. As a result, lorazepam may be better suited to prevent anxiety in people with generalized anxiety disorder.

Elderly patients may be more sensitive to the side effects of diazepam and related anxiolytics than younger adults. As a result, initial doses are usually reduced and increased slowly in the elderly to avoid excessive sedation and other unwanted side effects.

Precautions

Paradoxically, excitement, rage, anger, or hostility may occur in individuals taking anxiolytics for their calming effects. These reactions may occur secondarily to the relief of anxiety and usually occur within the first two weeks of therapy. If these reactions occur, anxiolytic therapy should be stopped.

Because suicidal tendencies may be present in patients who also have accompanying depressive disorders, only small amounts of anxiolytic agents should be dispensed at any given time to minimize the likelihood of intentional drug overdoses.

Side effects

Diazepam and related anxiolytics are often associated with drowsiness, sedation, confusion, and difficulty maintaining balance. These effects are more pronounced at the beginning of therapy and after dosage increases. People should avoid driving or performing tasks that require alertness until they know how the drugs will affect them.

When using anxiolytics like diazepam, fainting or dizziness sometimes occurs when a person stands up suddenly. Blurred vision may also occur.

When anxiolytics are used in high doses or taken with other drugs that depress the actions of the brain, such as alcohol or barbiturates, the normal breathing responses of the body may be interrupted and patients may stop breathing. For this reason, alcohol and other CNS depressants should be avoided in people taking diazepam and related anxiolytics. It is also best to avoid anxiolytics in those persons with a prior history of drug abuse or those who are suicidal.

Withdrawal symptoms will occur if patients stop taking anxiolytics suddenly. Patients should only discontinue using diazepam and related anxiolytics at the advice of their physician and the dosage of the drugs should be reduced slowly to avoid withdrawal effects.

Interactions

Diazepam will increase the drowsiness or sedative effects of other central nervous system depressants like alcohol or barbiturates. These combinations should be avoided.

Certain drugs, especially those eliminated by the liver, may interfere with the elimination of diazepam from the body. Anticonvulsants , antidepressants, numerous antibiotics, and cimetidine inhibit the elimination of most anxiolytics from the body, causing higher blood levels and increased side effects.

Resources

BOOKS

Drug Facts and Comparisons, 6th edition. St. Louis, MO: A Wolter Kluwer Company, 2002.

Kirkwood, Cynthia A. Anxiety Disorders. Pharmacotherapy: A Pathophysiologic Approach, edited by Joseph T. Dipiro, et al. Stamford, CT: Appleton and Lange, 1999.

Mosby's Medical Drug Reference. St. Louis, MO: Mosby, 1999.

Kelly Karpa, PhD, RPh