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Sedatives/hypnotics are drugs that depress brain function widely. They are commonly used and are prescribed for anxiety, seizures and muscle spasms. These are the sedative functions. Others are primarily used to help sleep, the hypnotic function. Through a round about way, they also increase dopamine effects in the brain and can cause a mild euphoria in some (but not all) patients
These drugs can be divided into several groups: barbiturates, which include phenobarbital, Fiorinal and Fioricet, tuinal and seconal; benzodiazepines, which include Valium, Xanax, Ativan, Klonopin, Restoril, Halcion among others; and barbiturate-like drugs, which include meprobamate, placidly, and Quaalude. Club drugs (date rape drugs) like GHB, GBL and Rohypnol likely fall into this last group as well. Soma, a commonly prescribed muscle relaxer, is metabolized to meprobamate in the body; it is addictive. Ambien, Lunesta and Sonata are in a different group. They have a different chemical structure than benzodiazepines but the same exact mechanism of action. Since they are very short acting, they are potentially more addictive
These drugs stimulate the type A receptor for the neurotransmitter GABA and slow brain cell action. This can reduce anxiety, wakefulness, muscle tension and spasm and produce desirable benefits in the short term. Side effects include over-sedation, clumsiness, memory and learning impairment. Elderly people will often become confused and are more susceptible to falls. Studies show increased mortality in those who use them-up to seven-fold, often due to increased confusion and injury. Combining them with other centrally acting drugs can worsen these side effects and even cause death.
The major problem that I see is not in overdose or misuse (Don't get me wrong, I see plenty of this, but it is not the main problem with these drugs.) However, most people who are prescribed these medications are compliant people who listen to their doctor, would never obtain medication from inappropriate sources and who truly feel the medications are helping them.
However, after 1-3 months the medication becomes less effective due to tolerance. Withdrawal soon follows with an increase in anxiety, insomnia, and muscle tension. Of course, when the next pill is taken, we feel better. This reinforces the impression that the medication provides an overall benefit; but often, the underlying physiologic process driving these symptoms is withdrawal. If a person has an additional problem of chronic pain, the pain will be worse as the pill wears off and be relieved when the sedative is taken again. This often leads to chronic pain resistant to all traditional measures.
The treatment is switching to a long acting agent (like valium or Librium) and slowly weaning. This process can take up to 2 years as faster weans are associated with an unacceptable rebound of symptoms. Withdrawal can last for months even after the drugs are stopped. Patients don't really appreciate the psychologic instability caused short acting sedatives until after this change is made, than they feel much better. What is sad is that many doctors do not realize the seriousness of these medications or how to wean patients off them.
The chronic use of sedatives causes abnormalities in our brain. Sedatives augment the GABA inhibition of the nerves which reduces nerve activity. Unfortunately, our brain adapts to their presence by making the nerves more likely to fire. If the sedative subsequently is withdrawn, the nerves increase their firing rate which can cause serious effects.
Sedative withdrawal refers to the physical and emotional symptoms we experience as the sedative leaves our body. Untreated sedative withdrawal usually begins 1-3 days after the last pill is taken (depending on which pill is abused), peaks at 3-6 days and then resolves after a week. Most people will experience tremulousness, anxiety, flushing, palpitations and high blood pressure. When high doses have been used, confusion can set in as well as hallucinations; these are serious complications that need to be discussed immediately with the doctor. Seizures may also occur.
Untreated withdrawal has serious consequences and could potentially be fatal. Because of the seriousness of withdrawal, I place people on an equivalent dose of a long acting sedative with less potential for abuse. This is usually Valium, Librium or phenobarbital. The dose is tapered over a few weeks or months.
There are a certain percentage of patients who cannot tolerate a short-term detoxification protocol. This is especially true if they have used a benzodiazepine consistently for over one year. They have long term irritability and/or anxiety. A slower detox over months may be a more optimal treatment. When the history of sedative use has been for multiple years of decades I have done detoxes that have lasted for more than a year.
1-Phenobarbital, Valium Librium- These medicines are long acting sedatives that reduce or even eliminate withdrawal. They also augment the GABA activity. They are used because they provide more consistent relief of withdrawal symptoms than other sedatives. They can cause over-sedation if the dose is too high. I base the starting dose on my estimates of what the patient’s tolerance is. The patient is seen within 7 days see how appropriate this dose is. If the dose is appropriate, the drug is gradually reduced.
2-Trazodone- this is a non-addictive anti-depressant medication that helps with sleeping. . A major side effect is persistent lethargy the following day, but only a small percentage of patients experience this. It can also affect the intestinal and urinary tracts as well as the heart but these problems are infrequently seen. Dose adjustments may be made depending on effectiveness
3- Neurontin or Depakote (gabapentin, Valproic acid)- These are anti-seizure medications that have been shown to reduce the intensity of sedative withdrawal. They are used in persons with a history of seizures; but they are also used to minimize the intensity of withdrawal symptoms. They are well tolerated. Some patients develop intestinal symptoms and a few others develop vague neurological symptoms but the majority of patients tolerate the medication. I do have to stop the medication about 25% of the time.
4-Clonidine-This medicine is not regularly used. It has the benefit of reducing high blood pressure or rapid heartbeats from withdrawal. It is also sedating and has a calming effect on patients. Its side effects include dry mouth as well as lightheadedness. The lightheadedness is especially likely to occur as you stand up. If the lightheadedness is occurring at other times, the dose may need to be decreased. Your response to this medication as well as any side effects will be monitored and the dosage may be adjusted accordingly.
5-Zyprexa, Seroquel, Abilify, Risperdal - These are very strong, non-addictive medications that help with anxiety irritability, and sleep. They are consider anti-psychotic drugs but their use has increased in past years because of their usefulness and relative safety
Older medicines in this class, like Thorazine or Haldol occasionally caused muscle spasms about the neck, face and tongue that may be experienced as a choking sensation. They may also cause increased restlessness. Zyprexa and Seroquel have a significantly lower chance of causing these problems.
Rarely, they may also cause a condition known as Tardive Dyskinesia which is a repetitive licking or smacking of the lips or tongue. This side effect is usually seen only after years of use at high dosages and is not really applicable to this treatment. There are rare reports, however, of this side effect occurring early in treatment. If this occurs, it is possible, however unlikely, that it may not be reversible. Despite this problem, millions have used these medications without adverse effect. I feel that the benefit in allowing a successful detoxification outweighs the risk posed by this side effect.
A more common side effect is weight gain which can lead to diabetes and/or cholesterol problems. Patients are monitored for these developments.
Sedative/ hypnotics are drugs that depress brain function. They due this by binding to the GABA receptors in the brain and augmenting their function. GABA receptors are ubiquitous in the nerve tissue of our body. They inhibit nerve cell firing. Every nerve has these receptors and they are always active. In fact, they represents the main control of our nerves. It is like driving a car. We can make the car go by easing off the brake. GABA represents that brake and without it we would lose control of all our brain functions. Even when the brake is weakened, we suffer serious effects.
There are many drugs that are considered sedatives. Some are prescribed for anxiety, insomnia, headache, seizures and/or muscle spasms. They are effective drugs but associated with tolerance and physical dependency. Many have been abused
The sedative drugs can be divided into the following groups:
Barbiturates, which include phenobarbital, Fiorinal and Fioricet, tuinal and seconal;
Barbiturates are the oldest class. They can be highly addictive. In addiction to their effect on GABA, they can also lead to release of dopamine. The dopamine release makes them more addictive. They are also easier to overdose on than other sedative. This is in part due to the fact that they can stimulate the GABA receptor to open even in the absence of natural GABA- this makes tolerance less of an issue with these.
Benzodiazepines, which include Valium, Xanax, Ativan, Klonopin among others;
Benzodiazepines are safer to use. In part, this is because they require the presence of GABA in order to work. On one hand they enhance the effect of GABA but on the other hand, they can also reduce the levels of GABA. This reduces their when compared to barbiturates . They are less euphoric than some of the barbiturates. They are safer.
Side effects include sedation, memory impairment and learning impairment. Elderly people will often become confused and are more susceptible to falls. At higher doses, anyone can develop ataxia (clumsiness) and vertigo. The combination of these drugs with alcohol can be fatal. In fact, the death rate in older Americans on these drugs is hugely increased when compared to those not taking the drugs
Z-drugs- Ambien, Lunesta Sonata.
While these are often considered different from medications like Xanax and klonopin- they have the same exact effect at the same exact receptors. The underling chemical structure is different so they are not technically benzodiazepines. However, since they do the same thing and have quick onset of action, they are potentially more habit forming. They are not often perceived as addictive as most people who use them regularly follow the instructions. Yet, when you look carefully at people who use these daily- they are often irritable in the evening and looking forward to bedtime when they can take their pill. This irritability at night often did not occur before they started these pills, and it resolves after they are off.
Barbiturate-like drugs, which include meprobamate, placidyl, Quaalude. Club drugs like GHB, GBL and Rohypnol likely fall into this group as well. Soma, a commonly prescribed muscle relaxer, is metabolized to meprobamate in the body; Soma is addictive.
Barbiturate-like drugs have not been as well characterized
Several of the barbiturate have been used as "date-rape" drugs. This means that they have an extremely rapid onset of action and victims are sedated quickly. They do not process memory so they are in a black-out f or that period and cannot remember afterward.
These drugs are very quickly metabolized. Patients can go from overdosed to mild withdrawal in a few hours. It can be very tough for these patients to stabilize; I have see these drugs used as often as 6-8 times daily.
People will take sedatives in doses much higher than recommended in order to get high. Others will gradually increase their dose over long periods. Still others stay at low dosages but remain on the medications for years. Physical dependency and withdrawal will occur in all these situations.
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I am often being asked to determine if a patient's use of a sedative if ok. Sometimes, it is a person coming off of a different drug who wants to know if it ok to stay on the sedative. Occasionally, I see a patient who has overdosed on a cocktail of drugs where the sedative is only one part. Many of these have overused their prescription or obtained medication from non medical sources.
However, I also see patients on long-term sedatives who stay within the prescribed amount. They often have kinds of symptoms and dysfunctions (albeit more subtle). How do thesepatients get into trouble?
At the start, a patient is given a sedative for anxiety. It can be quite effective. Because it works so well, a patient will want to use it more regularly. That is when a problem might start.
There will not be an issue if a drug is used intermittently. Once or twice a week will not be an issue- even if used for years. However, once you begin to use a drug almost daily, problems begin to become more common.
When we take a pill daily, or several times daily, we begin to take the medication for the wrong reason. We rationalize that we are anxious and that is why we are taking the medication. However, when we are taking the medication routinely, we will take it because it is time to take the medication. We are letting the clock decide when we take the medication, not how we feel. Even though the anxiety may not be extreme, we take it because we feel we should. After all, the doctor prescribed it to be taken this way. Many people congratulate themselves. They are allowed to take the medication 3-4 times a day and they are only taking it 1-2 times day. They think they can't get into trouble. When I point out to a patient they use the clock to decide when to take the pill, they shoot me down. They say they are always anxious and that is why they need the medication.
When we take the pill daily, it is always in our system and we will develop tolerance. Along with that, withdrawal will emerge. The withdrawal is subtle. It consists of an increase in anxiety and irritability. 4-6 hours later, we experience these symptoms which may be indistinguishable from the anxiety for which we began to use the medication in the first place. So we take more medication. Soon, we are taking the full amount of medication. Soon, that won't be enough.
Some patients will continue to increase their dosage, resorting to inappropriate behavior to obtain enough medication. Others will just tolerate the increased anxiety. They suffer and accept this anxiety as their lot in life. And they look forward to taking their medication for the brief episodes of reduced anxiety it provides. They never realize that a significant component of their suffering is the wearing off of the prior dose of medication.
Many patients and doctors will challenge me on this interpretation of events. It is anxiety they will say. Treat it with whatever medication is necessary. How do we know which interpretation is correct?
If a patient is feeling well overall, it does not matter. There is no reason to change treatment although some patients may want to consider slowly weaning.
However, if a patient is not feeling well than all possibilities for this lack of well being must be considered. They have often sought out multiple doctor's opinions to figure out what is wrong with them . When all other issues have been ruled out, many realize that it is the relative intoxication and withdrawal that is the cause of their chronic psychiatric and physical symptoms. Stabilization on long acting sedatives followed by slow tapering has been an answer for many.
There is another way that things often go awry. Sedatives can have a disinhibition effect on the people who take them. They will be more impulsive and act in ways they might regret. They move from an " I ought not" frame of mind to a "why the heck not" frame of mind. This leads to a slow increase in bad behaviors. Extra medication may be taken, people will eat more, and/or work may be avoided. One result is that people on sedatives show greater degrees of functional impairment and often use more medical care and resources.
This leads to one scenario I see regularly. A patient, who is stable on pain medication, begins to take a sedative (or increase their dose of sedative. Their normal inhibitions against taking medication is relaxed and we see an increase in drug use. This often culminates in excessive sedation, intoxication and occasional over dosage. I am regularly called to consult on patients who have overdosed. After I take a complete history, I invariably find the same thing.
It is always the sedative that starts the deterioration.