Understanding Benzodiazepines and How They Work

Medically reviewed by Lindsay Cook, PharmD

Benzodiazepines are a class of drugs (commonly referred to as “benzos”) prescribed to treat anxiety, panic disorder, seizures, insomnia, and alcohol withdrawal. They may also be used along with anesthesia during surgery.

Benzodiazepines work by targeting and binding to the gamma-aminobutyric acid (GABA) neurotransmitter in the brain. This slows the central nervous system (CNS), resulting in a calming, sedating effect.

This article will cover how benzodiazepines work, their side effects and safe use, their possible drug interactions, and alternative medications.

What Are Benzodiazepines Used For?

Approved indications for benzodiazepine use in adults include:

• Anxiety disorders, including generalized anxiety, short-term anxiety, and preoperative anxiety

• Panic disorder

• Status epilepticus or seizures in adults

• Alcohol withdrawal

Benzodiazepines also have a fair number of off-label uses. When a healthcare provider uses a drug approved by the Food and Drug Administration (FDA) for an unapproved use, that use is considered off-label.

Providers are generally able to use their medical expertise to prescribe FDA-approved drugs for unapproved uses as long as they judge that the drug is medically appropriate for you.

Examples of these uses with benzodiazepines include:

• Sedation in the intensive care unit (ICU)

• Short-term treatment of spasticity (muscle stiffness or rigidness) in children with cerebral palsy

• Use alongside antipsychotics, mood stabilizers, and antidepressants in treating psychotic disorder, bipolar disorder, and other mood disorders

• Chemotherapy-associated anticipatory nausea and vomiting

• Restless legs syndrome (condition causing a strong urge to move the legs)

• Tardive dyskinesia (side effect of medications causing involuntary repetitive movements)

• REM (rapid eye movement) sleep behavior disorder (sleep disorder causing physical and vocal acting out during REM sleep)

How Do Benzodiazepines Work?

Benzodiazepines, as a class, work on a certain type of receptor found throughout your brain and spinal cord, which make up the central nervous system.

This receptor is a protein called gamma-aminobutyric acid type A (GABA-A) receptor. Benzodiazepine drug molecules mimic the naturally occurring neurotransmitter GABA and bind to this receptor. This allows chloride ions to enter the neuron cells, which results in CNS depression. Outward signs of this include calmness, sleepiness, or drowsiness.

How quickly benzodiazepines begin to work depends on which specific drug you’re taking and how you’re taking it. Taken orally, most benzodiazepines are well absorbed. Some of the fastest-acting drugs in this class are:

• Valium (alprazolam)

• Halcion (triazolam)

• Xanax (diazepam)

Intravenous (IV) injection results in rapid onset of effects. Midazolam, in particular, is one of the most lipophilic benzodiazepines, meaning it rapidly crosses the blood-brain barrier (to enter your CNS).

Why Benzodiazepines Work

Benzodiazepines target and bind to a receptor in the brain and spinal cord called GABA-A by mimicking naturally occurring GABA. This is what causes the effects of CNS depression, like sleepiness and calmness.

These effects help relieve the symptoms of certain conditions it's used for, such as anxiety and panic disorder, and are why it is sometimes used for sedation.

Examples of Benzodiazepines

Benzodiazepines are often classified by their onset of action—how quickly they begin to work after you take them. This also affects their most common uses.

For example, midazolam is given by injection and often used alongside anesthesia medications because it works quickly to cause sleepiness. It is also commonly used as a nasal spray for both anesthesia and seizures.

In comparison, Klonopin (clonazepam) is taken by mouth and used more often for panic disorder and seizure prevention because it lasts longer and is usually taken two times per day.

Most Commonly Prescribed Benzodiazepines

The most commonly prescribed benzodiazepines are:

• Ativan

• Klonopin

• Valium

• Xanax

What Are the Side Effects of Benzodiazepines?

Side effects of benzodiazepines are somewhat common. For example, the following side effects have occurred in greater than or equal to 1% of people taking Xanax during clinical trials:

• Akathisia (restlessness)

• Dermatitis (skin irritation or rash)

• Dizziness

• Drowsiness

• Dry mouth

• Hypotension (low blood pressure)

• Increased salivation

• Light-headedness
  

Another commonly used benzodiazepine, Valium, has been associated with the following side effects:

• Blurred vision

• Confusion

• Constipation

• Headache

• Nausea

• Slurred speech

• Tremor

• Vertigo

Some more serious warnings exist for the benzodiazepine drug class as a whole. These include:

• Abuse, misuse, and addiction

• Dependence and withdrawal

• Depression

• Mania

• Respiratory depression in those with impaired breathing

How to Take Benzodiazepines Safely

While effective for various medical uses, benzodiazepines can sometimes cause side effects. For this reason, it's important to take them exactly as instructed by a healthcare provider.

However, here are a few general tips for taking benzodiazepines safely:

• Start at a low dose and frequency, and have another discussion with your healthcare provider no more than two to four weeks after you begin taking benzodiazepines to reevaluate effectiveness, side effects, and risks.

• Be careful about mixing benzodiazepines with other depressant substances like alcohol and opioids.

• If you take benzodiazepines on a regular, scheduled basis for several weeks or longer, do not stop taking them abruptly, as they need to be tapered down slowly to avoid withdrawal symptoms such as insomnia, anxiety, or tremor.

Benzodiazepine Use in Older Adults

The American Geriatrics Society (AGS) lists benzodiazepines as a class of medications that should be avoided in people 65 and older. Nevertheless, they're still occasionally prescribed to this population.

Use of these drugs in older adults comes with risks of dependence, cognitive deficits (or impaired thinking), falls, and car accidents.

These risks are even greater if benzodiazepines are used in older people who have a history of falls or who are already receiving two or more other CNS drugs (such as opioids, muscle relaxants, sleeping pills, or barbiturates, among others).

In cases in which benzodiazepines are necessary in an older individual, the most favored options are known as the “LOT drugs” (lorazepam, oxazepam, and temazepam). This is because they are shorter-acting and do not have active metabolites, making them less likely to cause residual or longer-term side effects.

Even in this case, the lowest effective dose for the shortest possible period will prove to be the safest in older adults.

Drug Interactions to Watch Out For

If you take benzodiazepines, be aware of potential drug or substance interactions. This includes:

• Alcohol: Alcohol is another depressant that also mimics the GABA neurotransmitter and can have a combined sedative or respiratory depressant effect if mixed with benzodiazepines.

• Sedatives like barbiturates (phenobarbital, pentobarbital): These medications that also bind to the GABA receptor and have a depressant effect can be dangerous when mixed with benzodiazepines.

• Opioids (such as hydrocodone, oxycodone, morphine): Opioids also suppress respiratory function and slow down your central nervous system. Combining them with benzodiazepines has been shown repeatedly in research to increase the likelihood of emergency room visits and death from drug overdose.

• Certain drugs called UGT inducers (e.g., carbamazepine, phenobarbital, phenytoin, and rifampin): These may make some benzodiazepines (e.g., lorazepam and oxazepam) clear from your system more quickly, reducing their effectiveness.

• CYP3A4 inhibitors like Prozac (fluoxetine), Luvox (fluvoxamine), oral contraceptives, ketoconazole, grapefruit juice, and clarithromycin: These may disrupt the clearance of benzodiazepines from your body, resulting in buildup, heavier sedation and potential worsening of side effects. If you also take these medications, you may get the same effects from a lower dose of benzodiazepines.

Advantages vs. Disadvantages

Benzodiazepines have both advantages and disadvantages to their use. While effective, they can come with potentially serious side effects and require some precautions when taking them.

Pros

• Effective at reducing anxiety

• Helpful for sleep problems

• Work well as muscle relaxants

• Can treat and prevent epileptic seizures

• Variety of options within the drug class with different onsets and durations of actions

Cons

• Potential for misuse, abuse, and addiction

• Has cognitive side effects, such as mental slowing and anterograde amnesia (difficulty forming new memories)

• Can be habit-forming and difficult to taper down the dose in people who have taken them regularly for more than a few weeks

• Not recommended for use in older people (65 and above) due to the increased risk of respiratory depression, excessive sedation, and cognitive effects

Alternatives to Benzodiazepines

Benzodiazepines are often prescribed for conditions like anxiety and insomnia, even though other treatments exist that show equal or better results with fewer risks and side effects.

A few alternatives to benzodiazepine therapy are:

• Psychotherapy and behavior modification (such as cognitive behavioral therapy, stimulus control, and sleep restriction) are the types of treatments that are recommended first-line for cases of anxiety and insomnia.

• Medications may be considered alongside psychotherapy for anxiety, but only serotonergic agents like selective serotonin reuptake inhibitors (SSRIs) are considered first-line medications.

• Vistaril (hydroxyzine) may be effective for anxiety and insomnia, as well as nausea and vomiting or allergies

Older adults are somewhat limited in options for safe medications due to the likelihood of side effects of many drugs worsening with age.

However, the AGS considers antidepressants Silenor (doxepin) and Remeron (mirtazapine) as good and safe options for treating insomnia in older people.

Summary

Benzodiazepines are a powerful medication class with a wide variety of indications and off-label uses, such as anxiety disorders, epileptic seizures, and insomnia, and for initiating anesthesia.

While effective for these purposes, benzodiazepines come with several important risks to consider. They are associated with dependence, misuse and abuse, cognitive impairments, and increased likelihood of severe side effects, particularly when combined with other depressant substances like opioids or alcohol.

The safest way to take benzodiazepines is on an as-needed basis rather than scheduled, at the lowest effective dose possible, and ideally for only a short period.

Speak with your healthcare provider about first trying safer, evidence-based alternatives such as cognitive behavioral therapy and other medications like antidepressants.

Read the original article on Verywell Health.