Benzodiazepines

What are benzodiazepines?

Benzodiazepines, sometimes referred to as benzos or BZDs, are a class of drugs used for their sedating and calming effects. There are several different benzodiazepines, each with varying uses, depending on how quickly they work and for how long the effects are felt ^[1].

Although they can be very effective medications, benzodiazepines can be associated with a risk of abuse or dependence. As such, they are typically not prescribed for long-term use, and there are guidelines for prescribing them safely ^[2].

What are benzodiazepines used to treat?

The FDA has approved the use of benzodiazepines in the treatment of several conditions. Due to their risk of addiction, It is advised not to use benzodiazepines long-term, so FDA guidelines suggest they are used for a limited time. Benzodiazepines are approved for use in the following ^[2][3]:

• Generalized anxiety disorder
• Social phobia
• Panic disorder
• Insomnia
• Seizure disorders
• As a premedication for surgery and other medical procedures

Benzodiazepines are often prescribed off-label, meaning they are prescribed for uses not approved by the FDA. This is typically due to increased risks of abuse and dependency or because the effectiveness and safety of their use in treating these conditions have not been determined. This includes conditions such as ^[4][5][6]:

• Alcohol withdrawal syndrome and detoxification
• Depression
• Mania
• Bipolar disorder
• Obsessive-compulsive disorder
• Schizophrenia and other psychotic disorders
• Attention-deficit/hyperactivity disorder (ADHD)
• Movement disorders, such as restless leg syndrome
• Eating disorders
• Chronic and acute pain
• Aggression and agitation in dementia

How do benzodiazepines work?

Benzodiazepines affect a neurotransmitter called gamma-aminobutyric acid (GABA). GABA is a neurotransmitter found throughout the body, including the brain, spinal cord, and central nervous system (CNS). It plays a vital role in the regulation of several functions, including cognition, mood, breathing, and blood pressure ^[7].

Benzodiazepines bind to GABA receptors, increasing the effects of this neurotransmitter. This reduces brain activity, causing sedating effects that impact mood, breathing, and muscles ^[1][8].

Benzodiazepines are categorized as short-acting, intermediate-acting, and long-acting. This refers to how long the medication stays in the body (half-life) and how long the effects are felt. Short-acting benzodiazepines leave the body faster, so they are commonly used for insomnia as they are less likely to cause ongoing effects the following day.

Long-acting benzodiazepines last for a long time, so they are used as ongoing anxiety treatments. These medications can cause a ‘hangover,’ as the sedating effects continue to be felt the following day or longer. However, they are less likely to cause withdrawal symptoms than short-acting benzodiazepines ^[1][9].

Additionally, the potency of benzodiazepines varies, with higher potency medications often working quicker than lower potency. High-potency benzodiazepines are usually fast acting and often used for acute symptoms.

As such, the type and dosage of benzodiazepine an individual is prescribed will depend on their condition and symptom severity, as this will impact how quickly and for how long the medication needs to be in effect ^[1][2].

Types of benzodiazepines

There are several benzodiazepines available for prescription in the US. These medications are often available in various forms, including tablets, dispersible tablets, oral liquids, nasal sprays, suppositories, and injectable liquids. Some of the more commonly prescribed benzodiazepines include ^[1][2][9]:

• Alprazolam: Alprazolam is available under the brand name Xanax. It is one of the most prescribed benzodiazepines. It works quickly and has a relatively short half-life, so it is often prescribed to treat panic disorder and acute anxiety symptoms.
• Lorazepam: Lorazepam is another fast-acting benzodiazepine used for acute symptoms such as panic attacks and acute agitation. It is available under the brand name Ativan.
• Midazolam: Midazolam works quickly and is very short-acting, so it is often used before operations as a sedative and anxiolytic rather than aa long-term  It is available in several forms and under the brand names Nayzilam, Seizalam, Dormicum, and Versed.
• Temazepam: Temazepam is fast-acting and is often used to treat sleep disorders such as insomnia. It is available under the brand name Restoril.
• Triazolam: Triazolam begins working quickly and is the shortest-acting benzodiazepine available. As such, it is often used to treat insomnia as it does not typically cause ‘hangover’ symptoms the following day. It is available under the brand name Halcion and is recommended for no longer than ten days of use.
• Clonazepam: Clonazepam is a long-acting benzodiazepine available under the brand name Klonopin. Due to its long-lasting effects, it is often used to treat anxiety disorders and is also effective at treating seizure disorders.
• Diazepam: Diazepam is a long-acting benzodiazepine available under the brand name Valium. It is often prescribed to treat anxiety disorders and is available in several forms.
• Clorazepate: Clorazepate is a long-acting benzodiazepine, available under the brand names Tranxene and Gen-Xene. It is often prescribed to treat anxiety disorders.
• Chlordiazepoxide: Chlordiazepoxide is a relatively long-acting benzodiazepine, often used to treat anxiety disorders and insomnia. It is available under the brand name Librium.

Side effects of benzodiazepines

When starting a new medication, it is common to experience some side effects. Generally, these side effects are not severe, but you should consult your doctor if they are persistent or concerning.

Short-term adverse effects of benzodiazepines include ^[10][11]:

• Drowsiness
• Dizziness
• Slowed breathing
• Weakness
• Confusion
• Impaired memory
• Unsteadiness
• Nausea
• Constipation
• Blurred vision
• Dry mouth

Occasionally, benzodiazepines can cause side effects that are the opposite of the intended effects of the medication, known as paradoxical effects. This includes ^[10][11]:

• Agitation
• Restlessness
• Erratic behavior
• Euphoria
• Irritability

Side effects of long-term benzodiazepine use can include ^[2][10][12]:

• Increased tolerance, resulting in withdrawal symptoms and a need for an increased dosage to feel the same effects
• Dependency
• Cognitive impairment, such as issues with memory and concentration
• Feeling disconnected from reality
• Feeling disconnected from emotions
• Reduced self-esteem and confidence
• Irritability
• Weight changes
• Urinary issues, such as incontinence or retention

If benzodiazepine use is abruptly stopped after being used regularly for an extended time, withdrawal symptoms can occur. Withdrawal symptoms can be unpleasant and even fatal in some cases and can last several days to several months.

Common benzodiazepine withdrawal symptoms can include ^[10][11][12]:

• Twitching and shaking
• Anxiety
• Irritability
• Blurred vision
• Muscle pain and stiffness
• Insomnia
• Nightmares
• Stomach pain
• Nausea
• Headaches
• Reduced libido
• Tingling in the hands and feet

Severe benzodiazepine withdrawal symptoms that may require professional intervention include ^[2][10]:

• Inability to speak or move
• Unusual or uncontrolled movements
• Psychotic symptoms such as hallucinations, delusions, and paranoia
• Mania
• Depression
• Suicidal thoughts
• Thoughts of harming others
• Seizures
• Increased heart rate and blood pressure

Risks and precautions

Abuse and addiction

Benzodiazepines are classed as a controlled substance due to their risk of abuse and dependence. The FDA has issued a black box warning to warn of the potential dangers of benzodiazepine use ^[2][9].

Regular benzodiazepine use over several days or weeks can lead to a physical dependence or addiction. This increases the risk of withdrawal symptoms when the medication is stopped and the risk of misuse, such as extended or increased use beyond the prescribed dosage.

To prevent or mitigate this risk, it is advised to use benzodiazepines for a short time and to ensure you follow your doctor’s recommendations and prescription ^[2][12].

Additionally, benzodiazepines are often misused by people for whom the prescription is not intended. Benzodiazepines are often sold as illicit drugs for recreational use to experience a ‘high.’ To try and mitigate this risk, repeat prescriptions are not provided and are written for limited use ^[2][9].

It is advised to keep benzodiazepines locked away or in a safe place to prevent them from being accessed by children or people for whom the prescription is not written.

The risk of benzodiazepine dependence and abuse is higher in those with an alcohol or substance use disorder, so it may not be appropriate for these individuals to be prescribed benzodiazepines ^[12].

Drug interactions

Benzodiazepines act as a depressant of the central nervous system (CNS), so it is advised to limit or avoid their use alongside other CNS depressant medications or substances. This includes alcohol, illicit drugs, opioid painkillers, sedatives, sedating antihistamines, anxiolytics, and anesthetics. Combined use of CNS depressants can result in breathing difficulties and may be fatal ^[11][12].

Benzodiazepines can also interact with other medications, impacting their effects. This includes oral contraceptives, antibiotics, antifungals, St John’s wort, anticonvulsants, antidepressants, and antipsychotics ^[1][11].

It is advised to inform your doctor of any medications used before starting benzodiazepine treatment.

Precautions

Inform your doctor if you have breathing problems, sleep apnea, heart, liver, or kidney problems, or a history of drug or alcohol use disorders. It may not be appropriate or safe for you to take benzodiazepines. Alternatively, you may require a reduced dose and careful monitoring throughout the duration of treatment ^[11][12].

Pregnancy and breastfeeding

There is a risk of fetal harm if benzodiazepines are used during pregnancy. Similarly, the medication can be excreted in breast milk, which can cause side effects or withdrawal symptoms in breastfeeding infants. As such, it is typically not advised to use benzodiazepines while pregnant or breastfeeding ^[11][12].

Your doctor may recommend an alternative medication or treatment to help you manage your condition or will reduce your daily dose to prevent harm to the fetus or newborn.

Alternatives to benzodiazepines

Many alternative treatments are available to help manage anxiety disorders and insomnia. Often, sleep problems are associated with anxiety symptoms, and many treatment options can improve both conditions ^[13].

Medications for anxiety

Several medications are available to help manage symptoms of anxiety disorders, including ^[13][14]:

• Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs) are often effective at treating anxiety disorders.
• Beta-blockers: Beta-blockers, such as propranolol, are often prescribed off-label to treat anxiety disorders. They can effectively reduce the physical symptoms of anxiety, such as a racing heart, sweating, and rapid breathing.
• Antihistamines: Antihistamines, such as hydroxyzine, can help manage anxiety symptoms.

Medications for sleep problems

Medications that can help reduce insomnia and sleep disturbances include:

• Sedating antihistamines: Hydroxyzine and cetirizine are antihistamines typically used to treat allergies. These medications can provide sedating effects, so they can help improve sleep quality ^[14].
• Over-the-counter medicines: Benadryl is an over-the-counter medication that has a sedating effect and can improve sleep ^[15].
• Melatonin: Melatonin is a natural chemical produced by the body that helps regulate the circadian rhythm or sleep-wake cycle. When melatonin release is decreased (usually by unnatural light, such as phones and television screens), it can be difficult to get to sleep. Melatonin supplements can improve sleep naturally and have few side effects ^[16].
• ‘Z’ hypnotics: ‘Z’ hypnotics are similar to benzodiazepines but work slightly differently and are considered safer. Commonly used nonbenzodiazepine hypnotics in this class include zaleplon (Sonata) and zolpidem (Ambien) ^[15][17].

Therapy

Engaging in psychotherapy, or talk therapy, can help improve anxiety symptoms. Various types of therapy are available, including cognitive behavioral therapy (CBT) and acceptance and commitment therapy (ACT). Improved anxiety symptoms can also help to reduce insomnia ^[13].

Self-help techniques

Utilizing self-help techniques can improve symptoms of anxiety and sleep disorders. This includes ^[13][16]:

• Relaxation techniques
• Mindfulness
• Yoga and meditation
• Breathing exercises
• Avoiding drugs, alcohol, and caffeine
• Regularly exercising

Sticking to a sleep schedule can also help reduce anxiety symptoms and improve sleep quality. This includes ^[16]:

• Going to sleep and waking up at the same time each day
• Sleeping in a dark and quiet room
• Avoiding screens before bed
• Doing something relaxing before bed, such as reading a book, meditating, or taking a bath
• Exercising during the day
• Avoiding caffeine before bed