We review and discuss common pharmaceutical dosage forms including tablets, capsules, buccal tablets, lotions, creams, emulsions, gels and more!
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 abuse of the 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 The withdrawal symptoms are usually seen if the drug is stopped cold turkey or withdrawn too fast.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
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 activty. As doses of benzodiazepines are increased, sedation turns into hypnosis.
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?
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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.
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 amount 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 decreases 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.
Benzodiazepine Effect On Sleep
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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 contributer 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 development of dependence and abuse. We will discuss this in the section below.
Side Effects Of Benzodiazepines
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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 and if they have any active metabolites (which we will discuss further down in the article).
List Of Benzodiazepines
|Drug (Brand Name)||Onset||Duration||Active Metabolites?|
|Estazolam (Prosom)||Intermediate||Intermediate||Yes (Minimal)|
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:
|Alcohol Withdrawal||A long acting drug such as Diazepam or Chlordiazepoxide. Lorazepam or Oxazepam are also recommended.||The most commonly used medication for this is diazepam due to it's quick onset and long duration of action.|
|Anxiety||Drug with a intermediate to long half life.||Short acting drugs are not typically recommended for as needed anxiety due to possible abuse concerns.|
Insomnia -Falling Asleep
|Temezepam or short acting drug||Temezepam has a 6-8 hour duration and no metabolites which makes it an ideal candidate for sleeping. There is a possibility of a next morning hangover effect if 8 hours is not devoted to sleep.|
Insomia - Staying Asleep
There is a possibility of a next morning hangover effect if 8 hours is not devoted to sleep.
|Panic Attacks||Clonazepam/Alprazolam||Most commonly used.|
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 sweating, fast heart rate, hand and foot tremors, insomnia, agitation, nausea, vomiting and rarely hallucinations. 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 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 are 2 recommended ways that have shown to be successful:
Taper 1: First, try to decrease your 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. Be your to monitor yourself for withdrawal symptoms or worsening of the condition being treated. If necessary, you can continue the present dose for a few extra weeks, or return to higher dose if needed.
Taper 2: Taper by 10% of your current dose every one to two weeks until 20% of the original dose is reached. From there, taper by 5% every two to four weeks thereafter.
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: weakness, headache, blurred vision, vertigo, nausea and vomiting, epigastric distress, and diarrhea; joint pains, chest pains, and incontinence. There are reported serious allergic, hepatotoxic, and hematologic reactions but the chance of these happening are quite low; these reactions have been associated with the use of flurazepam, triazolam, and temazepam. A side effect that must be considered when taking benzodiazepines is respiratory depression. Normal dosages can compromise respiration in patients who