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What's a Benzodiazepine?

By Dr. Eappen

 

Benzodiazepines are among the most prescribed tranquilizing drugs, and among the most misused and abused medications in the world.   According to the DEA, their street names include “Benzos, Downers, Nerve Pills and Tranks”.  Technically, they are classified as “sedative-hypnotic” drugs.  Sedative-hypnotics produce a temporary reduction in your level of consciousness for the purpose of inducing sleep, feelings of calm, and feelings of tranquility.

Alcohol is widely considered the oldest sedative-hypnotic in existence, and coincidentally, alcohol works very similarly to benzodiazepines.  Both are central nervous system (CNS) depressants, meaning they slow down brain activity.  They also both bind to the GABA receptor in our brain and spinal cord, to open the chloride channel.  What does that mean in real life?  At minimum, rapid relief in anxiety and insomnia.  While that sounds great in theory, it comes at a price.  Similar to alcohol, if benzodiazepines are used too frequently or in the wrong population, their transient positive effects can be quickly outweighed by negative side effects and long term consequences.

What Drugs are Benzodiazepines?  What are the Benzodiazepines Brand Names?

The five most common benzodiazepines I see prescribed in clinical practice, with their brand names in parentheses, include: lorazepam (Ativan), alprazolam (Xanax), clonazepam (Klonopin), diazepam (Valium), and temazepam (Restoril).  The DEA is in agreement with this benzodiazepines list, as they also cite these five as the most prescribed and most frequently encountered benzodiazepines in the illicit market.  The first benzodiazepine, chlordiazepoxide (Librium) was discovered in 1955, and is still frequently used today.  There are about thirty total types of benzodiazepines, and they are categorized according to their potency and half-life (speed at which they are eliminated from the body).  Five (5) half-lives are generally needed for a drug to be eliminated from the body.  Short acting benzodiazepines have a half life of 1-12 hours, intermediate is 12-40 hours, and long acting is 40-250 hours.  

The benzodiazepines are also classified by their potency.  The first benzodiazepines were low to medium potency.  These include chlordiazepoxide (Librium) and temazepam (Restoril).  Later, high-potency benzodiazepines were discovered, and were found to be more therapeutic in their effect, and have a faster onset of action.  Here is a list of benzodiazepines medications according to potency and half life:

  1. Alprazolam (Xanax): high potency, short half-life of 6-27 hours
  2. Lorazepam (Ativan): high potency, short half-life of 10-20 hours
  3. Clonazepam (Klonopin): high potency, long half-life of 18-50 hours
  4. Temazepam (Restoril): low potency, short half-life of 8-15 hours
  5. Diazepam (Valium): low potency, long half-life of 20-80 hours
  6. Chlordiazepoxide (Librium): low potency, long half-life of 5-30 hours

It may appear confusing that Librium is classified as having a “long half-life” at 5-30 hours,  while Xanax is classified as having a short half-life at 6-27 hours.  This is because some benzodiazepines (including Librium and Valium) get converted in the liver into “active metabolites”, whereas others (such as Xanax, Klonopin, Ativan) have no active metabolites. So while Librium may have a half life of up to 30 hours, one of its metabolites, “Desmethyldiazepam”, has a half life of up to 120 hours!

What is the Strongest Benzodiazepine?

The strength of a benzodiazepine depends on the dose prescribed, how it is administered (by mouth or by injection) and how you define strength in “strongest benzodiazepine”.  Although the benzodiazepines are classified based on potency and half-lives, a high dose, “low potency” benzodiazepine administered intravenously (through an IV in your arm) will have a much stronger effect than a low dose, high potency benzodiazepine that you take by mouth in pill form.  The former may cause a previously agitated person to fall asleep within minutes; the latter may provide a mild reduction in anxiety after about one hour. 

What are Benzodiazepines Used For?

The benzodiazepines are most often prescribed for treatment of anxiety and insomnia.  They produce almost immediate effects, and are ideal for short-term, intermittent, “as-needed” use for management of anxiety and insomnia.  Although they won’t work quickly enough to extinguish a panic attack (a panic attack will generally peak within 10 minutes and resolve within 30 minutes), the short term effects of benzodiazepines are helpful when used prior to planned, anxiety provoking events (i.e., prior to an MRI for those with claustrophobia, or prior to a flight for those with phobia of flying).  

The benzodiazepines are also widely prescribed for other reasons, such as muscle stiffness, sedation before surgery, detoxification from alcohol and other substances, and for rapid treatment of seizures.  During my internship after medical school, I did several months of training in inpatient (hospital based) neurology.  During this time, I gained plenty of experience in using benzodiazepines for seizures.   If someone was suffering from a seizure on the medical floor, it was common for us to order an injection of several milligrams of lorazepam (Ativan) to quickly stop the seizure.  

Adverse Effects of Benzodiazepines

The adverse effects of benzodiazepines are similar to those of alcohol, since they both work very similarly.  Risks of benzodiazepines include:

  1. Slowed movements and reactions: This may be especially pronounced in someone who is trying a benzodiazepine for the first time, or if someone suddenly increases their dosage beyond what they are accustomed to. These symptoms include drowsiness, poor concentration, slurred speech, muscle weakness and mental confusion.  Similar to alcohol, studies suggest that benzodiazepines slow reaction time and impair driving skills, causing increased risk of motor vehicle accidents in those who take these drugs. 
  2. Memory impairment: benzodiazepines can temporarily induce “anterograde amnesia”, which is an inability to form new memories.  This is one reason for their common use prior to surgery.  
  3. Reduced inhibitions: Increased excitement, irritability, aggression, hostility and impulsivity can occur in some individuals after taking benzodiazepines.  This may be due to reduced inhibition of behaviors normally suppressed by social restraints (as can be the case with alcohol).  These effects are more common in children, the elderly, and those with developmental disabilities. 
  4. Depression: There have been links between higher benzodiazepine doses and increased risk of depression.  Reducing the dosage or discontinuing the benzodiazepine can resolve the depressive symptoms. 

Long Term Side Effects of Benzodiazepines

Daily, long term use of benzodiazepines is generally frowned upon in medicine.  Long term benzodiazepines side effects include:

  1. Tolerance: Tolerance to the sleep inducing effects tend to develop quickly, which makes long term management of insomnia with these medications difficult.  Often, you may notice quick relief of insomnia initially, followed by gradual loss of the effect if taken nightly.  Tolerance to the anti-anxiety effect develops more slowly, but there is no evidence that benzodiazepines retain their effectiveness after 4-6 months of regular use.  After this amount of time, their use is often continued to treat withdrawal symptoms, which mimic the symptoms of anxiety.  This causes a desire to increase the dose to achieve the same initial effect, which maintains a cycle of tolerance and dependence that may be difficult to escape from. 
  2. Dependence: Psychologically, long term use of benzodiazepines may lead to overreliance on the need for the drug, loss of self-confidence, and varying degrees of drug-seeking behavior.  From a medical standpoint, these drugs can cause physical dependence when used long term, so rapid dose reduction or discontinuation of the drug can cause physical symptoms of withdrawal, which are further described below.  

The Benzodiazepine Withdrawal Syndrome

The withdrawal symptoms and timeline are similar to alcohol withdrawal.  Short-term withdrawal symptoms include anxiety, increased heart rate, increased blood pressure, tremors, sweating, insomnia.  The most serious acute benzodiazepine withdrawal symptoms include seizures and a phenomenon called delirium tremens, which can result in death.  These more serious conditions occur if someone abruptly stops benzodiazepines after long term, high dosage use.  These same conditions can occur if someone abruptly stops drinking alcohol after long-term, heavy use.  Because alcohol and benzodiazepines are so similar, we actually prescribe benzodiazepines for alcohol withdrawal treatment and for benzodiazepine withdrawal treatment.  The benzodiazepine withdrawal timeline corresponds to the half-life of the particular benzodiazepine being used; a shorter half-life leads to emergence of withdrawal symptoms far more quickly than a longer half-life.

My Take on Benzodiazepines

The benzodiazepines are effective at quickly alleviating anxiety and insomnia.  Because they are useful in the short-term and in a controlled environment, I frequently prescribe them in the hospital setting, where rapid reduction of anxiety, insomnia, and agitation are often needed.  However, in the office setting, I rarely prescribe these medicines.  They are too fraught with side effects–both short-term and long-term–that far outweigh their transient benefits.  Situations in which I do prescribe benzodiazepines include:

  1. Benzodiazepine taper: If someone comes into my office for a new consultation, and they have been on a high dose of benzodiazepines long term, I will typically recommend slowly tapering off these drugs.  Benzodiazepine taper guidelines typically include switching to a benzodiazepine with a long half-life, and reducing the dosage of the drug every week until discontinuing.  A benzodiazepine equivalency table can help guide the transition from one benzodiazepine to another.   There is no benzodiazepine equivalency table available online that I can recommend with confidence, so I am holding off on supporting a link to one.
  2. Intermittent use: I have many patients who I will prescribe low dose, as needed benzodiazepines to for anxiety provoking situations that occur intermittently but predictably, such as plane rides (if they have a phobia of flying). 
  3. Initiation of antidepressants (rare): On rare occasions, I will prescribe a benzodiazepine for either daily or as needed use when I first prescribe an antidepressant (SSRIs) for management of anxiety, and will limit the timeline of its use for no longer than two months after starting the antidepressant.  The reason for this is because A) antidepressants can take many weeks or months to take full effect, and B) sometimes antidepressants themselves can increase anxiety before they reduce it. 

If you have found that you are dependent or too reliant on benzodiazepines, and have realized that they are no longer as helpful as they once were, give us a call.  I have extensive experience in comfortably and safely tapering people off of these drugs, both in the hospital and office setting.  What do you have to lose?  Call us for a consultation, and let us help you feel well again.

About the Author

Seth Eappen, MD, is a board-certified adult, child and adolescent psychiatrist. Dr. Eappen completed medical school at the University of Illinois at Chicago and a residency at the University of Michigan, Ann Arbor. He completed his child psychiatry fellowship at MUSC in Charleston, SC, where he served as chief fellow. He is the founder of the Eappen Clinic, a private outpatient mental health practice with locations in Chicago and Oak Brook, IL.