Benzodiazepines:

Prescriptions for Anxiety

Introduction

Opioid Overdose Cases that Involve Benzodiazepines
30%

In 2017, close to 12.6 percent of the US population or nearly an eighth of Americans used benzodiazepines, according to Psychiatric Services in Advance.1 More than 30 percent of all opioid overdosage cases also involve benzodiazepines.2

Between 1996 and 2013, the number of adults who filled benzodiazepine prescriptions increased by 67 percent – from 8.1 million to 13.5 million. 4

Misuse of prescription drugs accounted for more than 17 percent of overall use. The quantity obtained also increased from 1.1 kg to 3.6 kg lorazepam equivalents per 100,000 adults.

Misuse of Prescription Drugs
17%

Defining Benzodiazepines

A class of prescription drugs that are used in treating medical conditions ranging from anxiety and seizures to alcohol dependence, benzodiazepines act on the central nervous system. Benzodiazepines are known to block excessive neural activity in the brain and other parts of the body’s central nervous system. While they all have a similar effect on the brain, each member of the benzodiazepines family has a distinct potency, making the length of effects different. That’s why some benzodiazepines are found to act better in comparison to others when applied to certain specific health conditions.

On the flip side, the sedative properties of benzodiazepines make them prime candidates for abuse when consumed in combination with alcohol and similar depressants. The situation is equally alarming in countries as far apart as the UK and Australia. Even developing countries have reported a growing incidence of abused benzodiazepines.

While diazepam or ‘Valium’ pills have been on the public radar for many years on account of their sedative and calming effects, flunitrazepam or the ‘date-rape drug’ has acquired notoriety in recent years because it is used in many sexual assaults.

History of Benzodiazepines

Benzodiazepines occupy a frontline position in the list of depressant medications most commonly prescribed in the United States. Doctors have no less than 15 types of benzodiazepine drugs to choose from when treating patients for an array of psychological and physiological health issues.

Every single type of benzodiazepine drug possesses the ability to act as an anxiety reliever, muscle relaxant, anti-convulsant, or hypnotic. In the United States, these drugs are listed under Schedule IV of the Controlled Substances Act.

Creation

Like in the case of many a pharmaceutical superstar, benzodiazepines were discovered by a quirk of fate. In the New Jersey laboratories of the Hoffman-LaRoche pharmaceutical company, Leo Sternbach noticed that when combined with methylamine, benzodiazepines formed a white powder that seemed to have a sedative, calming effect when fed to mice. Over the next couple of years, Sternbach developed several benzodiazepine drugs: diazepam, nitrazepam, flunitrazepam, and clonazepam. Diazepam or valium acquired near-iconic status and was even featured in a Rolling Stones hit number called ‘Mother’s Little Helper.’

By 1957, LaRoche launched Librium as an anti-anxiety medicine which the USFDA approved in 1960. Valium received government clearances in 1963. Soon other pharmaceutical majors hopped on the bandwagon and rolled out several benzodiazepines.

How Benzodiazepines Work

By attaching to a brain receptor, benzodiazepines activate nearby neurotransmitters which leaves the user feeling calm and sleepy. The entire process takes place within a few minutes after consuming the drug.

However, even when taken in prescribed doses and for the stipulated time-frame of 2 to 4 weeks, benzodiazepines can result in drug tolerance levels in users. Once abuse of the drug starts, discontinuation of the drug leads to serious withdrawal effects. That is why recovery from the drugs needs to be medically supervised in a controlled manner.

How Benzodiazepines are Taken

Benzodiazepines are administered in different ways depending upon the specific drug and purpose. They are prescribed for oral consumption – as a pill or in capsule form and as intravenous medication. They can also be injected into the muscle or administered as a suppository.

Types of Benzodiazepines

Benzodiazepines come in various types with varying used for the treatment of different health conditions. The most commonly prescribed benzodiazepine drugs are:

Diazepam

Better known as Valium, it used in treating anxiety disorders, alcohol withdrawal, muscle spasms, and seizure disorders. It is also used to induce controlled sedation. With a half-life of 20-100 hours, diazepam is categorized as a long-acting drug.

Lorazepam

A medium-acting drug with a half-life of 10-20 hours. Lorazepam is commonly prescribed for the treatment of conditions such as anxiety and seizures. It is also used as a short-term medication for insomnia. It is also prescribed for inducing controlled sedation in patients.

Alprazolam

Available as Xanax and Xanax XR, is a short-acting drug prescribed for treating anxiety and panic disorders. The drug has a half-life of 6-26 hours.

Clonazepam

Also known as Klonopin, Clonazepam used for treating seizure disorders, panic disorders, and neuralgia (nerve pain). Having a half-life of 20-50 hours, it is classified as a long-acting drug.

Clorazepate

With a half-life of 20-100 hours, Clorazepate is classified as long-acting drug. It is used to treat anxiety disorders, alcohol withdrawal, and partial seizures.

Midazolam

Available under the brand name Versed, which was subsequently discontinued. Midazolam is used for controlled sedation in preoperative situations. It is also used in general anesthesia induction and treatment of seizures. It has a half-life of 2.5 hours and is considered a short-acting drug.

Triazolam

Marketed under the brand name of Halcion, Triazolam is used in the short-term use of insomnia. It is a short-acting drug with a half-life of 2-5 hours.

Estazolam

Earlier available under the brand name ProSom, which was later discontinued. A medium acting drug with a half-life of 10-24 hours, it finds short-term use in the treatment of insomnia.

Temazepam

Available under the Restoril brand, is prescribed for short-term usage in tackling insomnia. It has a half-life between 10-20 hours and is categorized as a medium-acting drug.

Chlordiazepoxide

A half-life between 30-100 hours and denoted as a long-acting drug. Available under the brand Librum, it is commonly prescribed in anxiety disorder treatment and alcohol withdrawal.

Flurazepam

Used in the short-term treatment of insomnia. It has a half-life 40-100 hours and is a long-acting drug.

Common Uses

Alcohol Withdrawal

Benzodiazepines are usually the first resort for physicians treating cases of acute alcohol withdrawal. This is because these drugs significantly reduce the frequency and intensity of withdrawal symptoms. Many times, therapy with benzodiazepines has been known to be a life-saver for patients undergoing acute alcohol withdrawal systems ranging from tremors, anxiety, hallucination, delirium, seizures, and sleeping difficulties.

The most popular diazepine group drugs in treating alcohol withdrawal include diazepam, lorazepam, and chlordiazepoxide. Especially in patients suffering cirrhosis and other liver problems, medical professionals opt for oxazepam or lorazepam. While chlordiazepoxide, diazepam, and lorazepam can be administered orally, intravenously, or injected into the muscles, oxazepam can only be given as an oral dose.

Anxiety

Benzodiazepine-class drugs are extensively used to treat Generalized Anxiety Disorder (GAD), a health condition where the person suffers chronic, unfounded bouts of worry that are not attributed to other mental health issues or substance abuse. If the condition lasts for six months or more, it could be the onset of Generalized Anxiety Disorder.

GAD adversely impacts the normal daily routine of the patient, and symptoms include:

  • Insomnia
  • Muscle tension
  • Fatigue
  • Irritability
  • Restlessness
  • Lack of concentration

This health condition is quite prevalent in older people and is known to afflict roughly 7 million American adults. Unfortunately, while roughly 3% of the US population is afflicted with GAD, barely half of them receive treatment.

Diazepam, lorazepam, clonazepam, and alprazolam are the common benzodiazepines used for treating GAD. Due to the possibility of falls and fractures due to excessive sedation and confusion, benzodiazepines are prescribed with utmost caution in the case of elderly patients.

Insomnia

Apart from drastically reducing the time required to fall asleep, benzodiazepines also prolong the duration of sleep. 

Benzodiazepines must be used for periods between 2 to 4 weeks only, as long-term usage can lead to prolonged side effects. Short-acting benzodiazepines such as lorazepam are preferred instead of diazepam for treating insomnia. Along with the medication, patients are advised to stay away from sleep inhibiting habits such as late-night coffee and watching television before going to bed.

Panic Disorders

Panic disorder is a typical anxiety disorder that affects about 6 million American adults, or roughly 2.7% of the US population. The condition is characterized by repeated feelings of intense fear that are either expected or unexpected. 

Such symptoms are likely to trigger a variety of physical symptoms such as:

  • Rapid heart rate
  • Flushing
  • Sweating
  • Shortness of breath
  • Fear of death, or losing control

These physical symptoms mimic the body’s usual ‘fight or flight’ response mechanism to danger. Panic attacks may also be accompanied by mood disorders ranging from depression, anxiety, or those prompted by substance abuse.

Generally, benzodiazepines are prescribed initially to reduce the symptoms of panic disorders and thus allow antidepressants to initiate their impact. Diazepam, lorazepam, clonazepam, and alprazolam are effective in tackling this health condition. 

Treatments for panic disorders include selective-reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), along with behavioral therapy in some cases. 

Benzodiazepines are also used for a short period of time to avoid dependence. When treatment is complete, the dosage of benzodiazepines is gradually decreased so as to avoid withdrawal symptoms.

Medical Procedures

In procedural sedation, a combination of medications is administered to help relax the patient with a sedative and to block pain with an anesthetic in the course of medical or dental procedures. Benzodiazepines such as diazepam or midazolam are commonly used in such procedures. Such sedation is usually employed for outpatient surgery or procedures. Patients can return home the same day. 

Typical examples where benzodiazepines are used range from:

  • Endoscopy procedures
  • Biopsies
  • Wisdom tooth extractions
  • Uncomplicated surgical procedures that last an hour or less

Diazepam and midazolam are commonly used in such procedures. The patient is awake but in a sedated state and therefore, not in a position to recall the procedure. Patients are able to understand verbal cues or tactile commands and respond to them. In this type of sedation, the patient recovers more quickly from the effects of anesthesia. However, the drowsiness will persist for a day, and so self-driving is to be avoided at all costs.

Seizures

Benzodiazepines such as clobazam, clorazepate, clonazepam, midazolam, lorazepam, and diazepam are also deployed to treat seizures.

For acute or prolonged types of seizures known medically as status epilepticus, the first line of treatment is usually intravenous (IV) or rectal application of benzodiazepines if IV is unavailable. Status epilepticus comprises continued seizure activity for more than 30 minutes or two bouts of seizures devoid of consciousness in between them.

However, benzodiazepines are not recommended in the long-term treatment of epilepsy because of the risk of tolerance development in a high ratio of patients.

Side Effects and Withdrawal

Common Side Effects

As with most therapeutic drugs, benzodiazepines also induce a range of side effects – sleepiness, drowsiness or dizziness, and loss of libido being among the most common. Driving vehicles, operating machinery, or performing any hazardous tasks while receiving treatment with these drugs is a risky proposition and therefore should be avoided while using these drugs.

Unusual sleep behaviors are associated with traditional benzodiazepines. Similarly, the inability to create new memories could also occur with benzodiazepine usage.

The hangover effect or next-day drowsiness is a fallout of using benzodiazepines such as flurazepam or diazepam that have long duration effect. The sedative side effects can linger overnight and lead to disorientation during driving and other daily activities.

Withdrawal Effects

The onset of dependence on benzodiazepines is highly possible with prolonged use of therapeutic doses. In some cases, dependence can set in even after short-term treatment. Normally, it is best to gradually discontinue benzodiazepines to avoid withdrawal symptoms.

Withdrawal symptoms can include:

Sleep disturbances

Rebound insomnia

Restlessness

Irritability

Elevated anxiety

Hallucinations

Psychosis

Panic attacks

Headache

Tremors

Seizures

Generally, the withdrawal effects are noticed within 24 hours of discontinuing shorter-acting drugs. Here, the reactions are brief and comparatively more intense in nature. In the case of longer-acting benzodiazepines, withdrawal symptoms take longer to manifest. Symptoms typically begin a few days after the drugs are discontinued and peak after approximately seven days thereafter.

Withdrawal effects can be expected if the drug therapy, particularly those involving short-acting benzodiazepines, is discontinued suddenly. Sudden discontinuation could also result in rebound insomnia, making it difficult for the patient to sleep.

Intravenous (IV) benzodiazepines, if administered too rapidly, can be connected with cardiac arrest. 

Other possible reactions of IV administration include:

Hypotension or low blood pressure

Slow heart rate

Abnormal heart rates

Sleep apnea

Slowed breathing

Nausea/vomiting

Blurred or double vision

Some of the benzodiazepines (diazepam, chlordiazepoxide) contain active metabolites that stay in the system for longer periods, making it especially problematic for older patients. Elderly patients are likely to suffer from liver impairment. They could also have difficulty flushing out the drugs from their bodies.

Handling Withdrawal

Discontinuation of a benzodiazepine should be attempted gradually under a doctor’s guidance. Since sudden discontinuation or rapid withdrawal will raise severe symptoms, the process must always be done under the guidance and supervision of a trained medical practitioner.

The time required to successfully manage a benzodiazepine withdrawal depends upon a number of factors such as the type of benzodiazepine used, individual patient characteristics, the patient’s ability to handle withdrawal-related stress, and the original objective of the benzodiazepine use.

It may take between 4 weeks and six months to gradually bring down a benzodiazepine dosage. During this period, the dosage is reduced every week by not more than a quarter of the daily dosage. However, the ‘weaning away’ period can last for more than a year in some cases. Alternatively, patients can be prescribed diazepam or chlordiazepoxide in similar dosages to facilitate a smoother withdrawal.

Recovering from Addiction to Benzodiazepines

Recovery from addiction to benzodiazepines is hard.  There are many physical and emotional effects that can be distressing. 

Treatment facilities, like CNV Detox, can help make your recovery easier and help you stay sober.


Resources

  1. https://www.psychiatry.org/newsroom/news-releases/study-finds-increasing-use-and-misuse-of-benzodiazepines
  2. https://www.drugabuse.gov/drugs-abuse/opioids/benzodiazepines-opioids
  3. https://wonder.cdc.gov/
  4. Bachhuber MA, Hennessy S, Cunningham CO, Starrels JL. Increasing Benzodiazepine Prescriptions and Overdose Mortality in the United States, 1996-2013. Am J Public Health. 2016;106(4):686-688. doi:10.2105/AJPH.2016.303061