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Benzodiazepines: Overview and Use

Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Jan 8, 2024.

What are benzodiazepines?

Benzodiazepines are a class of medications that work in the central nervous system and are used for a variety of medical conditions, such as anxiety, seizures, and for alcohol withdrawal. Benzodiazepines work by blocking excessive activity of nerves in the brain and other areas in the central nervous system.

As a class, benzodiazepines are similar in how they work in the brain but have different potencies and durations of actions. Because of this, some benzodiazepines work better than others in the treatment of particular conditions. Common examples of benzodiazepines include alprazolam (brand: Xanax), diazepam (brand: Valium) and lorazepam (brand: Ativan).

Common benzodiazepine uses:

Benzodiazepines are a large drug class and have a long history of development, starting with the first FDA-approvals in the 1960s, chloridiazepoxide (Librium) and diazepam (Valium). There are many options available within the class, and most benzodiazepines are now available generically, making them affordable for most people.

All benzodiazepines are listed as DEA schedule IV controlled substances. As controlled substances, all benzodiazepines have the potential for abuse, addiction and diversion.

A Boxed Warning, the FDA's most stringent safety warning, exists on all benzodiazepine product information. When benzodiazepines are combined with other sedatives, opiates or alcohol, the risk of serious side effects such as profound sedation, respiratory depression, coma, and death may occur. Abuse, misuse, addiction, physical dependence, and withdrawal reactions greatly increases with use of this drug class. he Centers for Disease Control and Prevention recommends that doctors avoid prescribing Xanax and other benzodiazepines with opioid pain medication whenever possible.

Flumazenil is a benzodiazepine antagonist antidote that can be given intravenously in the emergency setting to reverse the effects of a benzodiazepine overdose.

Table 1 lists U.S. generic and brand name benzodiazepines, their common uses and duration of action. Many of the brand name products have been discontinued by their manufacturers; however, equivalent, lower-cost generics are available for these brands.

Related: Generic Drugs - Availability and Patent Status

Table 1: Common Benzodiazepines Available in the U.S.

Generic Name Brand Name Common Uses Half-life*(hours)
alprazolam Xanax, Xanax XR anxiety, panic disorders half-life 6-26 h (short-acting)
chlordiazepoxide Librium (brand discontinued) anxiety, alcohol withdrawal half-life 30-100 h (long-acting)
clobazam Onfi Lennox-Gastaut syndrome half-life 71-82 h (long-acting)
clonazepam Klonopin seizure disorder, panic disorder, neuralgia (nerve pain)

 

 half-life 20-50 h (long-acting)
clorazepate Tranxene anxiety, alcohol withdrawal, partial seizures half-life 20-100 h (long-acting)
diazepam Valium, Valtoco (nasal spray) anxiety, sedation, alcohol withdrawal, muscle spasm, seizure disorders half-life 20-100 h (long-acting)
estazolam ProSom (brand discontinued) insomnia (short-term use) half-life 10-24 h (medium-acting)
flurazepam Dalmane (brand discontinued) insomnia (short-term use) half-life 40-100 h (long-acting)
lorazepam Ativan, Loreev XR anxiety, insomnia (short-term use), seizures, sedation half-life 10-20 h (medium-acting)
midazolam Nayzilam (nasal spray); Seizalam (IM injection) preoperative sedation; general anesthesia induction; seizures half-life 2.5 h (short-acting); up to 7.2 h (active metabolite)
oxazepam Serax (brand discontinued) anxiety, alcohol withdrawal half-life 5-15 h (short-acting)
quazepam Doral insomnia (short-term use) half-life 39-73 h (long-acting)
remimazolam Byfavo procedural sedation lasting 30 minutes or less (adults) half-life 37 to 53 minutes (short-acting)
temazepam Restoril insomnia (short-term use) half-life 10-20 h (medium-acting)
triazolam Halcion insomnia (short-term use) half-life 2-5 h (short-acting)

*The half-life is the amount of time it takes for half of the drug to be eliminated from the body. The shorter the half-life, the quicker the drug is eliminated, and the faster any bothersome side effects can subside.

How do benzodiazepines work?

Benzodiazepines work in the central nervous system, selectively occupying certain protein areas in the brain called GABA-A receptors. There are three types of GABA (gamma-aminobutyric) receptors in the brain: GABA-A, GABA-B, and GABA-C. GABA is the main inhibitory neurotransmitter in the brain (a chemical that helps to block a nerve action). GABA helps to regulate movement, sight, anxiety, and many other brain functions.

Benzodiazepines open GABA-activated chloride channels and allow chloride ions to enter the neuron. This action allows the neuron to become negatively charged and resistant to excitation, which leads to the various anti-anxiety, sedative, or anti-seizure activity seen with these drugs.

Common uses for benzodiazepines

Alcohol withdrawal

Alcohol withdrawal is diagnosed in a patient with a history of heavy and prolonged alcohol use and a sudden reduction or complete abstinence from alcohol. Alcohol withdrawal produces changes in the body, such as:

Medications such as benzodiazepines are a first-line treatment for acute alcohol withdrawal. Benzodiazepines reduce withdrawal symptoms and may be life-saving for the patient. Commonly used medicines in this group include: chlordiazepoxide (Librium), diazepam (Valium), and lorazepam (Ativan). Lorazepam (Ativan) or oxazepam (Serax) may be preferred in patients with liver impairment such as cirrhosis. Chlordiazepoxide, diazepam, and lorazepam can be given orally, intravenously, or intramuscularly. Oxazepam may be useful but is only available orally.

Anxiety

Anxiety and worry is a common problem in adults; however, when chronic, unwarranted worry lasts for a period of six months or longer and interferes with normal daily activities, this may be diagnosed as Generalized Anxiety Disorder (GAD). GAD is the most frequent anxiety disorder, affecting 6.8 million adults or about 3% of the U.S. population, but more than half remain untreated. It can be very common in older patients.

Common symptoms of GAD include:

Drug treatment will depend upon the level of anxiety, patient characteristics such as age and organ function, and patient preference. For patients who do not want to use medications, cognitive behavioral therapy and relaxation therapy have been shown to be effective; however the combination may work best. Daily exercise has been shown to helpful for many patients with anxiety.

Antidepressants (SSRIs/SNRIs) are considered first-line therapy for most patients with anxiety, but benzodiazepines may play an adjunctive role in the treatment of GAD to address acute symptoms while the antidepressant takes effect. Only short-term use of low-dose benzodiazepines (2 to 6 weeks) is recommended, with a slow, gradual tapering once the antidepressant effect takes hold. Concerns about risks of tolerance, dependence, and diversion with benzodiazepines limit their usefulness in GAD. Benzodiazepines should be avoided in patients with a history of drug abuse.

Common benzodiazepines used for GAD include alprazolam, clonazepam, diazepam, and lorazepam. Mirtazapine (Remeron) and buspirone are also effective in GAD for patients who do not respond to at least two trials of SSRIs or SNRIs. Long-term use of benzodiazepines for GAD should be avoided, when possible, due to addictive risk.

Benzodiazepines should be used with extreme caution in the elderly due to the risk for excessive sedation, confusion, falls and fractures.

Insomnia

The benzodiazepine hypnotics shorten the time it takes to fall asleep and prolong the sleeping period. The main differences exist in how long they might remain in the body, possibly leading to prolonged side effects. For example, lorazepam has a much shorter duration than diazepam, allowing quicker clearance of the drug and theoretically less side effects. On the other hand, diazepam can remain in the system for days and boost the risk for long-term side effects, especially in the elderly.

The benzodiazepines that were initially FDA-approved for insomnia, such as temazepam (Restoril) or triazolam (Halcion), are not used as frequently today due to the availability of the newer nonbenzodiazepine drugs, such as eszopiclone (Lunesta), zolpidem (Ambien), or zaleplon (Sonata). All of the nonbenzodiazepine agents are approved only for the treatment of insomnia.

Muscle relaxant

The skeletal muscle relaxant class, which includes agents such as baclofen, carisoprodol (Soma), methocarbamol (Robaxin), metaxalone (Skelaxin), and cyclobenzaprine (Amrix), are typically used first-line when a muscle-relaxing effect is needed.

Benzodiazepines such as diazepam may also be used short-term as a muscle relaxant. These are generally used to relieve acute painful skeletal muscle spasms, such as what might occur with acute lower back muscle spasm. They are added as an adjunct to rest, physical therapy and / or heat and ice.

Panic disorders

Panic disorder is a specific type of anxiety disorder. In the U.S., about 6 million adults, or 2.7% of the population is affected. A person with panic disorder has panic attacks which are repeated episodes of intense fear which may be expected or unexpected. These symptoms may be accompanied by physical symptoms that are similar to the body's normal response to danger, often called the "fight or flight" phenomenon. Panic attacks may accompany other mood disorders such as depression, anxiety or substance abuse conditions.

Symptoms may include:

Panic disorder can be a prolonged, chronic disorder, but it is very treatable with medications that lessen symptoms. Behavioral therapy and treatment with the antidepressants such as selective serotonin-reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and/or behavioral therapy are first-line treatments.

The older tricyclic antidepressants, such as nortriptyline (Pamelor) and imipramine (Tofranil) are effective, too, but may be hindered by drowsiness and anticholinergic drug side effects, which can be especially problematic for older patients. In those without co-existing conditions such as depression or a history of substance abuse, benzodiazepines may be used cautiously for a short period of time.

Benzodiazepines may be used at the beginning of therapy to lessen symptoms while the antidepressants take effect, which may take 4 to 6 weeks. Benzodiazepines such as clonazepam (Klonopin), lorazepam (Ativan), diazepam (Valium) and alprazolam (Xanax) are useful for panic attacks. They are safe when used as directed and often bring quick relief from panic symptoms.

When discontinued, benzodiazepines should be slowly tapered to help avoid withdrawal symptoms like rebound insomnia and anxiety. The primary disadvantage of benzodiazepines is the risk of abuse, dependence, and overdose (especially with opiates). Selection of drug therapy should be based on issues with dosing, possible side effects or drug interactions, and cost.

Procedural sedation (also called conscious sedation)

Procedural sedation is the use of a combination of medications to help the patient relax (a sedative) and to block pain (an anesthetic) during a medical or dental procedure. Benzodiazepines such as diazepam or midazolam (Versed: brand discontinued) are often used.

In July 2020, remimazolam besylate (Byfavo) was approved by the FDA for the induction and maintenance of procedural sedation in adults undergoing procedures lasting 30 minutes or less.

This method of sedation is common for outpatient surgery or procedures that allow the patient to return home the same day, for example, endoscopy or colonoscopy procedures, wisdom tooth extractions, biopsies, and uncomplicated surgical procedures lasting less than one hour.

There is normally no need to aid breathing in conscious sedation; however, a deeper level of sedation may rarely occur, therefore respiratory and resuscitative equipment should always be available to healthcare providers.

The patient may remain awake but sedated, and usually there is no recollection of the procedure. Most patients can respond to verbal cues or tactile commands. This type of sedation allows the patient to recover more quickly from anesthesia. They will need someone to drive them home and are usually drowsy until the next day, so will need to take a full day off of work.

Seizures

Benzodiazepines are often used in the treatment of seizures - examples include:

For most types of acute or prolonged seizures or status epilepticus, an intravenous (IV) or rectal benzodiazepine would be the treatment of first choice.

Status epilepticus is considered a medical emergency in which there is either more than 30 minutes of continuous seizure activity; or there are two or more sequential seizures without recovery of full consciousness between two seizures.

Clonazepam is the benzodiazepine most frequently used for long-term control and prevention of chronic seizure disorders; however, in general benzodiazepines are not usually the first choice for seizure prevention.

Lennox-Gastaut syndrome is a severe form of epilepsy that usually begins in early childhood and also causes developmental and behavior problems.. This form of epilepsy may involve seizures of multiple types, mental impairment, and a particular brain wave pattern. Clobazam (Onfi) is used as an add-on (adjunct) benzodiazepine anticonvulsive treatment with other seizures medications in the treatment of Lennox-Gastaut syndrome.

Nayzilam (midazolam) and Valtoco (diazepam) are nasal sprays now approved for the treatment of seizure clusters (also known as acute repetitive seizures). Nayzilam is approved by the FDA to be used in patients 12 years of age and older, and Valtoco in used in those 6 years and older.

Common side effects of benzodiazepines

Drowsiness, sleepiness, or dizziness are the most commonly reported side effects with this drug class. Driving or operating machinery or perform other hazardous tasks can be dangerous while using these drugs. Drinking alcohol in combination with benzodiazepines may heighten these effects.

Unusual sleep behaviors and anterograde amnesia may occur with traditional benzodiazepines. Anterograde amnesia is the loss of the ability to create new memories, leading to a partial or complete inability to recall the recent past. Several benzodiazepines are known to have this powerful amnesic effect; triazolam (Halcion) is notorious.

Next day drowsiness and "hangover effect" is a concern with benzodiazepines that have long duration, for example, with diazepam or flurazepam. The sedative side effects can carry into the next day and impair driving and other daily activities; this is a particularly concerning risk in the elderly.

More recent research is focusing on the possible adverse effects on cognition (thinking and reasoning ability) in patients using benzodiazepines for long periods of time. In some patients, severe allergies like anaphylaxis and angioedema have been reported with benzodiazepines.

Related: Side Effects of Benzodiazepines

Overall, benzodiazepines should be used short-term as they can lead to tolerance, abuse, dependence (addiction), withdrawal and possible fatal overdose when combined with opioids.

Potent benzodiazepines with shorter elimination half-lives (triazolam, alprazolam, lorazepam) may be the most prone to causing problems with tolerance and dependence.

Withdrawal reactions can also occur if the drug is stopped suddenly, especially those that are shorter-acting. Discontinuation of a benzodiazepine should be done gradually under a doctor's direction.

Sudden discontinuation can also lead to rebound insomnia, making sleep difficult, and leading to continued use and higher doses of benzodiazepines.

Intravenous (IV) benzodiazepines can be associated with cardiac and/or respiratory arrest if they are given too rapidly. Other reactions due to IV administration may include:

Use in the Elderly

Some benzodiazepines (diazepam, chlordiazepoxide) have active metabolites that remain in the system for an extended period (long-acting), and this can be problematic for patients, especially older patients. Elderly patients may have liver impairment and trouble eliminating the drugs from their system. Side effects, such as dizziness, confusion or unsteadiness may persist in the elderly who are prescribed long-acting benzodiazepines.

In the elderly, benzodiazepines and nonbenzodiazepine agents should be avoided, as recommended by the Beers Criteria, an expert opinion-developed guideline addressing safe drug use in the elderly.

If there is a documented need, low doses and drugs with shorter durations (half-lives) will help to minimize side effects like dizziness, weakness, and falls that may lead to hip fractures. Under the care of a clinician, there may be appropriate uses for benzodiazepines in the elderly, such as for seizure disorders, certain sleep disorders, benzodiazepine or alcohol withdrawal, severe anxiety, procedural anesthesia, and end-of-life care.

Drug interactions with benzodiazepines

Important: Many drug interactions can occur with benzodiazepines. A review of all medicines for drug interactions should be completed by a healthcare provider each time a new drug is added or discontinued in any treatment regimen.

Traditional benzodiazepines can be associated with overdoses and fatal consequences when combined with alcohol, opioids, other sedatives, or illicit drugs. While it is rare that an overdose of benzodiazepines by itself would be fatal, when combined with other drugs that depress the central nervous system, the risk dramatically increases.

Examples of other drugs that may be additive to the central nervous system depression if combined with benzodiazepine include:

As noted in the Boxed Warnings, concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.

Many traditional benzodiazepines are broken down in the liver and when combined with drugs that block this action, blood levels can rise, leading to side effects. Lorazepam, oxazepam and temazepam are less likely to have this risk due to fewer liver enzyme interactions.

However, there are many other potential interactions, so a drug interaction screen with your pharmacist or doctor is needed. Patients should not stop using any medications, including benzodiazepines, without first contacting their doctor. Abrupt discontinuation of benzodiazepines may lead to severe withdrawal symptoms.

Herbal and grapefruit interactions

Herbal supplements and grapefruit can have significant interactions with certain benzodiazepines. Examples of some of the more common interactions include:

Always consult your healthcare provider about how drug interactions should be managed before making any changes to your current medications.

Benzodiazepine Use in Pregnancy and Breastfeeding

Pregnancy

In general, benzodiazepines should NOT be used in pregnancy.

The FDA has phased out pregnancy category risks (A, B, C, D and X), and instead includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. View the pregnancy section of each individual drug monograph to determine pregnancy risk or benefit.

Benzodiazepines were previously placed in FDA Pregnancy Category D, meaning a positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. Under the direction of a physician, certain benzodiazepines may be given in very serious and life-threatening situations like status epilepticus.

Breast feeding

Women who are breastfeeding should not use benzodiazepines unless directed to do so by their physician. Benzodiazepines may accumulate in breast milk and in breastfed infants. Some benzodiazepines may be appropriate therapy in women who are breastfeeding, but only under the direction of a physician.

Learn More: Medicine use while Breastfeeding

Flumazenil use as a benzodiazepine antidote

Flumazenil is used to reverse the sedative effect of a benzodiazepine when used for a medical procedure and for treatment in a benzodiazepine overdose. Flumazenil blocks the central effect of benzodiazepines by competitive interaction at the benzodiazepine receptor site. A patient experiencing a benzodiazepine overdose may have the following signs and symptoms:

The use of flumazenil in benzodiazepine overdose is controversial and the risks may outweigh any possible benefit.

Benzodiazepines are often coingested with other substances, such as opioids and alcohol, in overdose. In addition, in patients who are tolerant or dependent to the effects of benzodiazepines, the use of flumazenil may precipitate severe benzodiazepine withdrawal symptoms and seizures; therefore, its use is contraindicated in these patients.

Benzodiazepine Withdrawal

Physical dependence on benzodiazepines, can occur after prolonged use of therapeutic doses, or even after a short treatment period in some patients. In general, benzodiazepines should be discontinued slowly to minimize symptoms such as:

Shorter-acting drugs produce a brief and more intense withdrawal reaction that usually begins within 24 hours of discontinuation. Longer-acting benzodiazepines have a slower development of withdrawal symptoms that typically begin several days after discontinuation, but peak at about 7 days.

The length of time required to complete a benzodiazepine withdrawal depends upon individual patient characteristics, type of benzodiazepine, ability to handle stress involved with withdrawal, and original reason for benzodiazepine use. The time needed to taper off of a benzodiazepine generally ranges from 4 weeks to 6 months, but can exceed a year in some circumstances.

Rapid withdrawal can lead to a syndrome of severe symptoms in many patients. At all times, benzodiazepines should be discontinued under the care of a physician.

Costs of benzodiazepines

Most benzodiazepines are available in a generic form which can lead to cost-savings for patients. In general, benzodiazepines are used for short-term treatment.

If cost is a concern for any medicine, be sure to speak to your physician before prescriptions are written and discuss options with your pharmacist, as well. Online coupons and manufacturer's patient assistance are other options. Remember that drug prices are subject to change at any time and may differ among pharmacies. Always check with your local pharmacy for exact pricing. Many pharmacies may not accept coupons for controlled substances.

Which benzodiazepines are available outside the U.S.?

Other international benzodiazepines are available that are not approved for use in the U.S. Each generic may have multiple brand names associated with the product, and the brand names may vary between countries. Internationally available benzodiazepines have similar uses as those approved in the U.S., such as for anxiety, for sleep or sedation, use for surgical premedication, for seizures, and panic attacks. International benzodiazepines include:

Rohypnol (flunitrazepam) is an intermediate-acting benzodiazepine with general properties similar to those of Valium (diazepam). It not available legally in the U.S., although it can be found legally in other countries where it is used for the treatment of insomnia and as a pre-anesthetic. Rohypnol is used illegally to lessen the depression caused by the abuse of stimulants, such as cocaine and methamphetamine, and in cases of sexual assault where is induces memory loss in the victim. It is often referred to as the "date rape" drug.

Benzodiazepines and Online Fraud

Online Internet pharmacies are increasingly a danger to patients and their health. Fraudulent and counterfeit medications are often marketed and sold online to unsuspecting consumers. Beware of online pharmacy purchases; in general, consumers in the U.S. should only purchase medications from their local pharmacy or health-plan administered mail-order pharmacy.

To help identify an unknown pill or capsule, use the Drugs.com Pill Identification Wizard. If you cannot identify your medicine, it may be fraudulent; contact your healthcare provider for further information.

This is not all the information you need to know about benzodiazepines for safe and effective use and does not take the place of your doctor’s directions. Discuss any medical questions you have with your doctor or other health care provider.

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Further information

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