Antianxiety Drugs: 20 Big Side-Effects You Must Know

Antianxiety Drugs

DEFINITION

Antianxiety drugs, or anxiolytics, are medicines that calm and relax people who suffer from excessive nervousness, tension, or anxiety.

They also are used for short-term control of social phobia disorder or specific phobia disorder.

Traditional antianxiety drugs known as benzodiazepines have, to a large extent, been superseded by selective serotonin reuptake inhibitors (SSRIs).

PURPOSE

Antianxiety drugs can be used to treat mild transient bouts of anxiety and more pronounced episodes of social phobia or a specific phobia.

Several symptoms characterize clinically significant anxiety.

For example, people may experience marked or persistent fear of one or more social or performance moments when they are exposed to unfamiliar people or possible scrutiny. They may respond in a humiliating or embarrassing way.

Vulnerability to the feared situation produces an anxiety attack. Fear of these anxiety episodes leads to avoidance behavior, impairs normal social functioning, including school or work, even though patients are aware that their fears are unjustified.

In addition to anxiety and phobias, antianxiety drugs—particularly the short-acting, benzodiazepines lorazepam and midazolam—may be used to relax patients before medical or dental procedures.

They reduce the need for other agents, including analgesics, anesthetics, and muscle relaxants before and after surgery.

In addition to their use as Antianxiety drugs and sedatives, benzodiazepines are used as muscle relaxants to manage fibromyalgia and restless leg syndrome in treating epilepsy, insomnia, and alcoholism.

Buspirone, an azapirone drug, is used to treat generalized anxiety disorder.

DESCRIPTION

Benzodiazepines are central nervous system (CNS) depressants that enhance the effects of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter in the brain that reduces neural activity.

Thus, benzodiazepines can reduce anxiety and have sedative, sleep-inducing, muscle-relaxing, and anticonvulsant properties.

They can be short-, intermediate-, or long-acting. Lorazepam, alprazolam, and clonazepam are appropriate for treating mild anxiety, social phobia, and specific anxiety disorders.

Diazepam is still widely used for anxiety, but its active metabolite desmethyldiazepam has a long half-life, making it a poorer choice than other drugs in this class.

Treatment of anxiety in psychiatric practice has largely turned from traditional benzodiazepines to antidepressant therapies.

SSRIs—including citalopram, fluoxetine, fluvoxamine, escitalopram, paroxetine, and sertraline—have milder side-effect profiles and less risk of dependency than benzodiazepines.

SSRIs increase the concentration of the neurotransmitter serotonin in the brain.

However, SSRIs may require three to five weeks to take effect and must be taken continuously. In contrast, benzodiazepines can produce a response within 30 minutes and maybe be dosed on an as-needed basis.

Thus, traditional anxiolytics remain useful for patients who need a rapid onset of action or whose exposures to anxiety-provoking stimuli are infrequent enough not to require ongoing treatment.

Tricyclic anti-depressants and monoamine oxidase inhibitors (MAOIs) are older types of antidepressants that can effectively treat anxiety.

Commonly used tricyclics include imipramine (Tofranil) and clomipramine (Anafranil).

The most frequently used MAOIs are isocarboxazid (Marplan), phenelzine (Nardil), and tranylcypromine (Parnate).

Buspirone (BuSpar), which is not chemically connected to other classes of CNS drugs, is a classic anxiolytic. However, it is considered either a third-line or adjunctive agent to SSRIs and benzodiazepines when other treatments have proved ineffective or in patients who should not use benzodiazepines because of a history of substance abuse.

Benzodiazepines are controlled drugs under U.S. federal law, whereas buspirone is not a controlled substance and has no established abuse potential.

Buspirone, like other antidepressants, requires two to three weeks of use before there is clinical evidence of improvement and must be dosed continuously to maintain its effects.

Beta-blockers, which are frequently used to treat cardiovascular conditions, are sometimes used for anxiety disorders.

In particular, they may be prescribed for social anxiety disorder, for example, to reduce fear of speaking in front of an audience. Propranolol (Inderal) is a commonly used beta-blocker.

U.S. brand names

U.S. brand-name benzodiazepines include:

• Ativan (lorazepam)
• Centrax (prazepam)
• Dalmane (flurazepam)
• Diastat, Valium, Zetran (diazepam)
• Doral (quazepam)
• Halcion (triazolam)
• Klonopin (clonazepam)
• Librium (chlordiazepoxide)
• Niravam, Xanax (alprazolam)
• Onfi (clobazam)
• Paxipam (halazepam)
• Prosom (estazolam)
• Restoril (temazepam)
• Serax (oxazepam)
• Tranxene (clorazepate)
• Versed (midazolam)

U.S. brand-name SSRIs include:

• Brisdelle, Paxil, Pexeva (paroxetine)
• Celexa (citalopram)
• Lexapro (escitalopram)
• Luvox (fluvoxamine)
• Prozac, Rapiflux, Sarafem, Selfemra (fluoxetine)
• Zoloft (sertraline)

Canadian brand names

Canadian brand-name benzodiazepines include:

• Ativan (lorazepam)
• Dalmane (flurazepam)
• Halcion (triazolam)
• Restoril (temazepam)
• Rivotril (clonazepam)
• Valium (diazepam)
• Xanax (alprazolam)
• Versed (midazolam)

Canadian brand-name SSRIs include:

• Celexa (citalopram)
• Cipralex (escitalopram)
• Luvox (fluvoxamine)
• Paxil (paroxetine)
• Prozac (fluoxetine)
• Zoloft (sertraline)

RECOMMENDED DOSAGE

Benzodiazepines shall be administered 30–60 minutes before exposure to anticipated stress. Dosages are distinguished to reduce sedation.

The usual dose of alprazolam is 0.25–0.5 mg. The normal dose of lorazepam for anxiety is 0.5–3 mg. Doses may be repeated if necessary.

The pre-surgical dose of midazolam differs with the method of implementation, the patient’s age and the physical shape of the patient, and the other drugs to be used. 

For patients under age 60 that haven’t been treated with narcotic analgesics, a dosage of 2–3 mg is usually adequate. Still, certain elderly patients can respond to a dose being as low as 1 mg.

 The normal dose of lorazepam is considered 4 mg, administered by intramuscular injection a minimum of two hours before surgery. 

If the medication is given intravenously, a dose of up to 2 mg may be given 15–20 minutes before surgery.

Dosages of SSRIs vary considerably with the specific drug, the individual, and the condition being treated.

SSRIs are commonly started at low doses, with gradual dosage increases at regular intervals until an appropriate plateau has been reached.

Tricyclic antidepressants are likewise started at low dosages that are gradually increased as needed.

Buspirone is originally dosed at 5 mg three times a day. Dosages should be regulated based on clinical response, with increases of 5 mg/day at intervals of two to three days, as needed, not to exceed 60 mg/day.

PRECAUTIONS

Benzodiazepines can be habit-forming and may require increasingly higher dosages to remain effective. Therefore, they are generally used only for short periods.

They should not be administered to patients with histories of substance abuse disorders.

There is significant variation among persons in the metabolism of benzodiazepines, so the patient response may not be predictable.

Benzodiazepines are sedatives and should be avoided by people who must remain alert. Doses must be gradually reduced before completely stopping these drugs.

Patients with psychosis should not be treated with Benzodiazepines, also having acute narrow-angle glaucoma or liver illness. 

The medicaments can act as respiratory depressants and should be avoided in patients with respiratory conditions.

These medications should not be used during the second and third trimesters of pregnancy. Nevertheless, usage thru the first trimester appears to be safe.

They should not be taken while breastfeeding. There are specialized warnings for the use of benzodiazepines in children.

Alprazolam, lorazepam, and clonazepam are among the most prescribed medications for seniors.

There is concern that benzodiazepines may be prescribed in place of antipsychotics for sedation in seniors with conditions such as dementia, especially in nursing homes.

The American Geriatrics Society discourages their use for insomnia, agitation, or delirium in seniors because they can be disorienting and habit-forming with long-lasting effects in older people.

However, their use may be appropriate for treating seizure disorders, severe anxiety, or withdrawal symptoms, as well as in end-of-life care.

In 2016, (FDA) the U.S. Food and Drug Administration issued strong new warnings against combining benzodiazepines with opioid analgesics because of the risk of suppressed breathing and coma or death.

Amidst 2002 and 2014, the number of patients prescribed both opioids and benzodiazepines increased 41%, representing an escalation of more than 2.5 million patients.

Between 2004 and 2011, there was a significant increase in emergency department visits by people using drugs for nonmedical purposes and a tripling in overdose deaths from the combination of drugs.

Furthermore, the death rate from benzodiazepine overdoses increased more than fivefold in the United States between 1996 and 2016.

SSRIs are considered safer than both benzodiazepines and older antidepressants.

They are specific for serotonin, unlike tricyclic antidepressants and MAOIs that affect many different neurotransmitters, receptors, and neural processes.

Albeit, they should not be used by people with certain medical conditions. There are warnings about using SSRIs in people under age 25 because of a possible link to suicidal thoughts and behaviors.

Furthermore, SSRIs remain in the body for some time after the medication is stopped, and they can cause “discontinuation syndrome” if stopped abruptly.

Therefore, the dose is gradually decreased before being completely discontinued.

Buspirone causes drowsiness, so patients should not drive or operate machinery until they know how the drug affects them.

Buspirone gets metabolized in the liver and excreted over the kidneys and must be used cautiously in patients with hepatic or renal disease.

SIDE EFFECTS OF ANTIANXIETY DRUGS

Side effects of benzodiazepines can include:

• sedation and sleepiness
• depression
• lethargy
• apathy
• fatigue
• light-headedness
• memory impairment
• disorientation or confusion
• restlessness
• crying or sobbing
• delirium
• headache
• slurred speech
• weakness
• poor coordination
• stupor
• seizures
• dizziness, vertigo, or syncope (fainting)
• various muscle and mental impairments
• coma

SSRIs have lesser side effects than older antidepressants used for anxiety disorders.

The most common side effects include nausea, nervousness, and sexual dysfunction, which usually disappear as the body adjusts to the drug.

Buspirone has a low occurrence of side effects. Drowsiness and dizziness are among the most reported adverse reactions.

The drug also may cause difficulty sleeping, nervousness, light-headedness, weakness, excitement, fatigue, depression, headache, fast or irregular heartbeat, blurred vision, or unusual movements of the head or neck muscles.

INTERACTIONS

Benzodiazepines must not be used in combination with alcohol or street drugs because of the risk of serious or life-threatening reactions.

They can interact with various other drugs. Benzodiazepines carry warning labels concerning increased risk for life-threatening breathing problems, sedation, or coma if used in combination with opiates for cough or pain.

The doctor and pharmacist should be notified if patients are taking any of the following medications:

• medications for anxiety, mental illness, or seizures
• sedatives
• sleeping pills
• tranquilizers
• antidepressants
• barbiturates such as secobarbital (Seconal)
• droperidol (Inapsine)

SSRIs interact with many other drugs and herbal remedies, especially other drugs that affect mood.

Some drug interactions can be serious. A combination of fluvoxamine and clozapine (Clozaril) can cause low blood pressure and seizures.

Alcohol can increase SSRI-induced drowsiness and should not be used when taking some SSRIs.

Interactions between SSRIs and MAOIs can cause potentially fatal seizures and blood pressure, and heart irregularities.

In accession to antidepressant MAOIs, the antibiotic linezolid (Zyvox) is an MAOI. There must be a minimum of two weeks between stopping one drug and starting the other drug.

A three-week interval should occur between an MAOI and either paroxetine or sertraline if each of two types of anti-depressants were taken for over three months.

 Due to its long half-life in the body, it is necessary to wait five to six weeks after halting fluoxetine before starting an MAOI.

Before taking any anxiolytic or antidepressant, patients should review all their medications—prescription, nonprescription, and herbal—with their prescribing physicians and pharmacists.

Seldomly, certain drugs may interact with an SSRI to cause excessively high levels of serotonin, a serious or life-threatening condition known as serotonin syndrome.

Some of the other drugs and herbal remedies that can interact negatively with SSRIs include:

• other antidepressants
• antihistamines
• various medications for anxiety, mental illness, or seizures
• sedatives and tranquilizers
• sleeping pills
• St. John’s wort

In addition to interactions with SSRIs, MAOIs can interact with various foods and beverages that contain tyramine and with numerous medications, including certain pain relievers and cold and allergy remedies.

Buspirone levels in the body are increased by concomitant use of erythromycin, itraconazole, and nefazodone.

The use of buspirone along with an MAOI may cause severe blood pressure elevation and should be avoided.

KEY TERMS

Anxiety— Worry or tension in response to real or imagined stress or danger. Physical reactions such as fast pulse, sweating, trembling, fatigue, and weakness may accompany anxiety. Anxiolytic— Antianxiety drug.Benzodiazepines— A class of antianxiety drugs.Buspirone— An antianxiety drug that is unrelated to benzodiazepines and other anxiolytics.Central nervous system (CNS)— The brain and spinal cord.Epilepsy— A brain disorder with symptoms that include seizures.Gamma-aminobutyric acid (GABA)— The major inhibitory neurotransmitter in the central nervous system.Monoamine oxidase inhibitors (MAOIs)— Antidepressants that increase serotonin, norepinephrine, and dopamine.Neurotransmitter— A chemical that transmits impulses across synapses between nerves.Phobia— An intense, abnormal, or illogical fear of something specific such as heights or open spaces.Seizure— A sudden attack, spasm, or convulsion. Selective serotonin reuptake inhibitor (SSRI)— a type of antidepressants, such as fluoxetine or sertraline, inhibits the inactivation of the neurotransmitter serotonin by blocking its reuptake by neurons. Social phobia— Social anxiety disorder; fear of social situations. Tricyclic antidepressants— Medications used to treat mental depression and other conditions, including anxiety disorders.

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