Benzodiazepines, as a class of medications, are among the most commonly prescribed and used drugs around the world. They are used for a variety of indications such as insomnia, anxiety disorder, seizure disorder, sedation, muscle relaxation, and alcohol withdrawal.
There are more than 10 different medications in the benzodiazepine class and many people have trouble understanding just what the differences are among all the different drugs.
Within the class, the drugs are primarily differentiated based on how quickly they act on the body and how long you can expect each dose to last.
Our list below contains 3 different items:
- How quickly the drugs work
- How long they last
- If they have any active metabolites (which we will discuss further down in the article).
Now that we have every benzodiazepine listed, we want to discuss in depth the many different aspects of them including how they work, side effects, dependence problems, and withdrawal symptoms.
How Do Benzodiazepines Work?
Benzodiazepines exert their effects based on actions within the central nervous system. They are typically classified as central nervous system depressants. Specifically, they bind to an inhibitory neurotransmitter in the brain known as GABA (Gamma-Aminobutyric Acid).
When drugs bind to this neurotransmitter, it produces a variety of effects including but not limited to sedation, hypnosis, decreased anxiety, relaxation, amnesia, and anticonvulsant activity. As doses of benzodiazepines are increased, sedation turns into hypnosis.
Benzodiazepine Effect On Sleep
One of the most common uses of benzodiazepines is for sleep. When taken before bedtime, they reduce what is known as sleep latency, otherwise known as the time to fall asleep.
They also decrease the number of times you wake up during sleep and decrease stage 0 sleep (which is a sleep stage in which you are considered "awake").
According to sleep studies, they also reduce stage 4 and REM sleep. They do not affect the normal secretions of hormones that occur during usual sleep. Patients generally report that the use of the medication gives them a feeling of both a refreshing and deep sleep.
The usefulness and effectiveness of medicating before sleep typically decrease with chronic use so, for most people, it is important to only take the medication as needed for insomnia.
Patients who chronically take the medication and then stop cold turkey usually notice a decrease in total time asleep as well as an increase in the times they awaken throughout the night.
Side Effects Of Benzodiazepines
Most users of benzodiazepine drugs experience some sort of side effect, at least initially. At usual dosages, you may experience varying degrees of light-headedness, slowed motor function, slowed reaction time, impairment of mental functioning and confusion.
It is extremely important to note that when combined with alcohol, these side effects become much more pronounced. These side effects typically affect the elderly more so than younger adults.
In addition to the side effects already listed, benzodiazepines have also been known to cause the following:
- Blurred vision
- Nausea and vomiting
- Epigastric distress
- Joint pains
- Chest pains
A side effect that must be considered when taking benzodiazepines is respiratory depression.
Normal dosages can compromise respiration in patients who have COPD, asthma or sleep apnea. In the news and popular culture, drugs such as Valium and Xanax are typically associated with deaths caused by overdosages.
What many do not know is that benzodiazepines are rarely fatal, even with overdoses, unless other drugs are taken at the same time. Alcohol is a common contributor to deaths in which benzodiazepines are also taken.
Lastly, while rare, it is worth mentioning that benzodiazepines can sometimes cause effects you wouldn't think possible to their inhibitory effect on the central nervous system. Paradoxical effects such as nightmare, anxiety, irritability, fast heart rate, and sweating have all been reported.
Again, these side effects are very rare are have really been only associated with very rapid-acting drugs such as triazolam.
Despite their adverse effects, benzodiazepines are actually fairly safe medications. Having said that, Chronic benzodiazepine use poses a risk for the development of dependence and abuse. We will discuss this in the section below.
Dependence And Withdrawal
Chronic use of benzodiazepines can cause a physiological dependence and occurs as a natural consequence of regular use over a long period of time. Being dependent on these drugs does not automatically imply the abuse of drugs. It's tough to put a specific time period of use that puts people at risk for dependence.
Sometimes it can happen in as short as 3-6 weeks while other times it can take 6 months to a year of continuous treatment. The risk increases with higher dosages. The withdrawal symptoms are usually seen if the drug is stopped cold turkey or withdrawn too fast.
As a general rule of thumb, withdrawal symptoms are worse with drugs that have a short duration of action such as alprazolam and triazolam.
So, what are the symptoms of withdrawal?
For shorter-acting benzodiazepines, the main concern is rebound anxiety and seizures. Most people are not at risk of seizures unless they have a history of them, but it is still possible.
Other symptoms of withdrawal include:
- Fast heart rate
- Hand and foot tremors
Many studies have attempted to find the best way to taper the medication with the fewest side effects.
There is currently no concrete recommendation as to what to do. If you have been on a benzodiazepine for some time and are going to be stopping it, your doctor should be the one giving you advice on how to ween down.
The following two tapering methods have been discussed in clinical studies and may be an option:
- Decrease your current dose by about 25% for the first week, then by 25% the second week.
- After the second week, decrease by about 10% every week thereafter.
- Taper your current dose by 10% every one to two weeks until 20% of the original dose is reached.
- From there, taper by 5% every two to four weeks thereafter.
For both of these tapering methods:
- During the tapering process, be sure to monitor yourself for withdrawal symptoms as well as a worsening of the condition you are treating (e.g. anxiety).
- If withdrawal symptoms are difficult or you notice your condition worsening, you could continue the present dose for a few extra weeks, or return to a higher, previously well-tolerated dose if needed.
In our chart at the beginning of the article, we had a column for metabolites. Drugs that last a long time in the body and have many active metabolites are usually not recommended for people with liver problems or the elderly.
These two groups will have a harder time eliminating the drug from their body and over time, these metabolites, which are products of the parent drug after being broken down, can accumulate in the body and possibly cause side effects.
Diazepam is a common culprit of this and for this reason, it is rarely used in the elderly population.
Is There A 'Best' Benzodiazepine?
There really is no "best" benzodiazepine, since they are really only differentiated by how fast they work and how long they work in the body.
There are some recommended ones for certain indications which we will list here:
- Benzodiazepine Pharmacology and Central Nervous System–Mediated Effects. AccessFDA
- Benzodiazepine Toxicity. NEJM
- Challenges of the pharmacological management of benzodiazepine withdrawal, dependence, and discontinuation. PubMed
- Management of benzodiazepine misuse and dependence. PubMed
- Benzodiazepines—an overview. PubMed
- Benzodiazepines I: Upping the Care on Downers: The Evidence of Risks, Benefits and Alternatives. PubMed
- Benzodiazepines and Z-Drugs: An Updated Review of Major Adverse Outcomes Reported on in Epidemiologic Research. PubMed