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Other Risks of Sleeping Pills Chapter 2 of The Dark Side of

Udocheals.orgAmbien depression
3.16.2017 | Logan Blare
Ambien depression
Other Risks of Sleeping Pills Chapter 2 of The Dark Side of

If the sleeping pill is in the blood during the day, it will make the daytime brain less active and less functional. T he side effects of the prescription sleeping pills are much like their benefits. Besides, a large percentage of people who take sleeping pills do often get up at night, at a time when the sleeping pill could cause falls or confusion. At night, we want our brain cells to stop working (unless we need to get up in the middle of the night), so sleeping pills make the brain less active. The problem is that no sleeping pill remains in the blood all night, impairing consciousness, and then suddenly evaporates at the moment of awakening. Most of the marketed prescription hypnotics, when taken at bedtime, will remain in the blood with at least half strength when morning comes.

leave the blood fast enough to be largely gone from the blood by morning: these include zolpidem (Ambien), zaleplon (Sonata), and triazolam (Halcion). Perhaps this is because a percentage of people have genetic variations in their metabolism of sleeping pills which may cause dangerous concentrations to linger. Ambien CR may sometimes affect people the next morning, and eszopiclone (Lunesta) is likely to produce a few hours of morning impairment, particularly among people over age 60. On January 10, 2013, the FDA issued a warning recommending that the usual dose of zolpidem (Ambien) be no more than 6.25 mg for women. Even these drugs may be found in the morning blood if they are taken in the middle of the night. Oddly enough, despite the brief half-life (time to be half-dissipated) of zolpidem, zaleplon, and triazolam, there is fragmentary evidence that these short-acting hypnotics produce impairments lasting after their disappearance from the blood. The FDA had finally discovered that a percentage of patients have enough zolpidem in the blood the next morning to impair performance such as driving. Only a few prescription hypnotics marketed in the U.S. Ramelteon (Rozerem) produces no next-day impairment according to the manufacturer studies, but one well-controlled independent European study showed impairment in driving performance.

By Daniel F. Kripke, M.D.

Unfortunay, physicians don’t give lollipops to adult patients. The decision had to do with the doctor-patient relationship, not with any particular complaint or medical diagnosis. Giving sleeping pills is often a gift-giving behavior which is part of the “bedside manner.” When a distinguished group of physicians from our national Institute of Medicine were asked which times they would give a patient a sleeping pill, they said it was when they knew the patient well. They give sleeping pills instead, when a big lemon sucker might do less harm. When I was a child, my pediatrician would give me a lollipop at every visit to compensate for the pain of the injections I was likely to receive.

In fee-for-service medicine, it is also quite clear where the doctor’s financial interest lies. I don’t want to blame the physicians alone. Patients like to receive gifts! They like to feel that they are taking something which might help, even if there is no scientific evidence. I am certain that most physicians try to be ethical about sleeping pills, but they also realize that the patient given a sleeping pill is likely to return for a renewal prescription, whereas the patient refused a sleeping pill may look for another doctor. Doctors are fond of their patients and like to keep them. When I talk to physicians about sleeping pills, they l me these stories again and again. In fact, patients often insist that they need sleeping pills, and may become quite irate if a doctor does not want to provide what the patient wants.

When one of the long-acting drugs is taken every night, the blood concentrations accumulate day by day, increasing for up to 10-20 days, reaching much higher concentrations than after the initial dose. The problem of daytime impairment is more severe with the longer-acting drugs such as flurazepam (Dalmane) and quazepam (Doral), because the active by-products of these drugs remain in the blood day after day following only a single dose. Therefore, with flurazepam (Dalmane) and quazepam (Doral), and also with diazepam (Valium) and chlordiazepoxide (Librium) when they are taken nightly as sleeping pills, daytime impairment accumulates after consecutive days of use.

The sleeping pill industry would like you to believe that insomnia leads to depression, which might be true some of the time. This means that sleeping pills cause people to have more depression. Perhaps the common mechanism is that insomnia leads to sleeping pill use, which in turn leads to depression. They imply that sleeping pills might prevent depression. It isn’t so. The controlled trials of zaleplon, zolpidem, eszopiclone, and ramelteon mentioned in the FDA NDA documents show a higher rate of developing depression among those given the sleeping pills as compared to those given placebo. It has been proven very clearly that sleeping pill use is associated with very high suicide rates, but as yet, the evidence that sleeping pills cause increased suicide is based on the strong evidence that the pills cause depression, as well as very high rates of suicide observed among those known to have taken sleeping pills. Another side effect of sleeping pills is depression.

Mortality and Cancer Risks, Which Pills to Avoid & Better Alternatives.

2.E. The problem of addiction.

In a few reported cases, people intoxicated with Ambien have climbed into their cars and engaged in sleep driving. Of course, this is not amusing if it leads to obesity, which can be a life-threatening condition, or if they eat something unhealthy. Hallucinations have been reported with zolpidem, zaleplon, and eszopiclone. For example, a successful businessman told me that while taking Ambien, he might have absoluy no recollection of a conference which his own notes showed that he had attended. In the more amusing examples, they may sleep-walk to the refrigerator and stuff themselves with strange foods that they would not normally eat in such quantity. From viewing various reports, I now realize that these terrible side effects may develop in about 1% of users of sleeping pills. Because sleeping pills turn off our brain cells – not always in all parts of the brain to an equal extent – they can make people do some mighty strange things. We now realize that sleeping pills can cause some very strange and disastrous side effects. At other times, people receiving sleeping pills have become confused or disoriented. Another odd symptom is complete amnesia for events, even during the day. For example, having taken Ambien, people can act like somnambulists or sleep walkers. Unfortunay, the behavior of the so-called Ambien Zombies is not always harmless. Some of the accidents were bad, and the police did not like how the zombies behaved.

The psychological effects are to make us sleepy, reduce alertness and vigilance, slow reaction times and judgment, and impair aspects of inligence and memory. Further, there is extensive evidence that sleeping pills on average impair performance and memory on the following day. As explained above, sleeping pills suppress the action potentials of a wide variety of brain cells. To summarize an extremely complex group of studies, almost all sleeping pills produce immediate impairments of memory and performance. Literally hundreds of studies have been done concerning the psychological effects of sleeping pills, both within a few hours after ingestion and then during the day following taking a sleeping pill at bedtime.

To repeat, as a generalization, taking sleeping pills at bedtime impairs how people perform on the following day.

That was not a big improvement. Part of the reason that the sleeping pills showed no significant benefit after 14 days was that the placebo group had improved. Remarkably, after 9 or 14 days of administration, there was no statistically-reliable increase at all in the sleep of the volunteers taking Dalmane or midazolam as compared to those receiving placebo. Perhaps regular sleep habits and the belief that they were being helped had produced this improvement, and possibly, placebo patients improved because they had been two weeks longer off the benzodiazepines they had been previously taking, which might have been making them worse. As expected, these chronic insomniacs slept about 20-27 min. This is an important point, because the fact that a person taking a sleeping pills is sleeping more than at an experimental baseline does not mean that the pill is working, a point confused in many of the most-quoted studies. The volunteers had become tolerant to the sleeping pills, which had lost their effect. more for the first two days they were given Dalmane or midazolam than when given the placebo. In any case, after two weeks, the groups receiving Dalmane and midazolam were not significantly improved compared to placebo patients.

Sleeping pills impair daytime thinking. 2.A.

Sleeping pills generally make function WORSE the next day.

This study implied that after several weeks of use, people may take sleeping pills not because they continue to benefit in any way, but because their sleep becomes so much worse when they withdraw. Even though the volunteers receiving triazolam were no longer sleeping better than those given placebo at the end of 5 weeks, when the drugs were stopped, those who had received triazolam developed a drug-withdrawal insomnia which made them worse than those who had taken placebo. This study was interesting because it studied the period of withdrawal after the research drugs were stopped. It hurts too much to stop. In effect, they have become habituated or addicted to sleeping pills. A rather similar study of chronic insomniacs receiving flurazepam (Dalmane) or triazolam (Halcion) also showed that after several weeks of use, the drugs were no better than placebo.

To view sleeping pill advertising, you might imagine sleeping pills help you to work better, think better, or function better the next day. With very few exceptions, controlled studies supported by the manufacturers show that sleeping pills make test performance WORSE on the following day, or have no effect on performance. This is deceptive. See if you can find any evidence that these drugs improved next-day performance for people with insomnia. Look through the FDA files for Ambien, Lunesta, Sonata, and Rozerem, at the FDA website.

On tests reflecting driving performance, these sleeping pills would have made the patients less safe drivers. Moreover, by 14 days, both drugs were making performance significantly worse. The small increase in sleep which Dalmane and midazolam produced on the first two nights of administration was not sufficient to produce any improvement in performance, which was measured the following mornings with a variety of sophisticated testing methods.

In the CPSI study, about 1/3 of people who said that they took sleeping pills “often” said that they never had insomnia. Even if we include all diagnoses related to emotional problems and nervousness, most patients given sleeping pills were not given any diagnosis suggesting a genuine medical reason for the prescription. This suggests that gift-giving explains much hypnotic prescribing. Before doctors were required to write in a diagnosis justifying every prescription, only a small percentage of patients given sleeping pill prescriptions received any diagnosis related to sleep disorders.

The hope that these powerful hypnotics would increase sleep in these chronic insomniacs (for even 2 weeks) was disappointed.

These patients were self-deceived about the value of the medication, almost deluded, thinking the medicines made them better when they actually made them worse. The volunteers themselves said that they thought the research sleeping pill was good and that it was helping them, even when objective tests and at times, their own family observed that the hypnotics were making them worse. This study yielded a very interesting observation in these chronic insomniacs who for years had believed in sleeping pills. That is a lesson in the misperception of sleeping pill users. Even the group receiving placebo said that placebo was a good sleeping pill which they would like to use again. The group receiving either Dalmane or midazolam liked their pill a bit more than the placebo was liked, even although the active drugs were worse for the patients than placebo.

After several weeks of use, those taking this sleeping pill were sleeping better when they took the drug but then worse when they skipped it. Testing intermittent use (3 times a week), a recent study showed a similar result with zolpidem (Ambien). Overall, after several weeks of use, their sleep was averaging no better than a group taking inactive placebo.

There would be no way of knowing for certain if Halcion was the explanation, but I wouldn’t be surprised if the murderer had been a Halcion Zombie. One wonders if these reports have been most common with Halcion and Ambien because they were the market leaders, but it is interesting that both drugs are absorbed and removed from blood at about the same speed. Similar lapses in memory and strange behaviors were reported frequently when triazolam was the most popular sleeping pill. I do not think that these strange symptoms are unique to the new non-benzodiazepine hypnotics such as zolpidem, though in 2006, Ambien was getting most of the bad publicity. A lawyer once asked me to consult with her client in the jail, where he was awaiting trial for having murdered his sister. I am inclined to think that these disastrous side effects are not so uncommon and can occur with any prescription sleeping pill (though we do not know yet about ramelteon or doxepin). The lawyer said her client thought that the Halcion (triazolam) he had been taking had caused him to commit this irrational crime, because otherwise he had no idea why he had done it.

As compared to heroin, the withdrawal syndrome may be more lasting with the hypnotics, perhaps more than a month in some cases, though too little controlled experimentation has been done to be really sure. By addicting, we mean that these drugs have two properties. Severe withdrawal of sleeping pills can produce death. On the other hand, zolpidem (Ambien) seems less prone to cause withdrawal symptoms than the barbiturates or benzodiazepines. All prescription hypnotics (with the exception of ramelteon and the new drug Silenor) may be physically addicting drugs, and all are sometimes attractive to drug addicts. First, when we take addicting drug such as narcotics or barbiturates, we develop tolerance so that a given dosage has less and less effect or “stops working.” People who develop tolerance are prone to increase their dosage more and more. The risk of seizures and death is probably more severe with withdrawal of barbiturates than with benzodiazepines. The withdrawal symptoms of hypnotics such as barbiturates and benzodiazepines are very well known. In one sense, the withdrawal syndrome with hypnotics can be worse than withdrawal from heroin, because while the heroin addict experiences withdrawal as a terrible anguish, it is rare that addicts do not survive even the most severe heroin withdrawal. I frequently see this problem with long-term users of sleeping pills. Second, addicting drugs cause physical withdrawal symptoms when they are stopped abruptly. They include shakiness and tremor, nervousness and anxiety, panic, hyperactivity and increased reflexes, rapid heart rate, and epileptic seizures and death in the most severe cases.

Remarkably there has been only a smattering of evidence in special conditions that any sleeping pill ever improves daytime performance. A person’s hope and belief that a prescription sleeping pill will improve the person’s function on the next day is consistently betrayed. It simply does not work. Even when it is possible to show that sleeping pills increase sleep (a little) and even though the short-acting drugs are gone by morning, sleeping pills generally do not improve people’s ability to function in their lives. In the hundreds of studies where the pharmaceutical industry has studied hypnotic effects on waking function, the emphasis has been on trying to reduce impairments caused by these products, not on assisting people’s ability to carry on their lives. The few experiments where sleeping pills seemed to produce transient improvements in performance often involved models of jet lag and shift work, not the common problem of the aging person with insomnia.

Disastrous side effects. 2.C.

Because these two studies were focused on the kinds of people who are actually chronic users of sleeping pills, it was particularly disturbing that the active drugs did not produce long-term benefit (only deleterious effects). It was particularly revealing that the volunteers thought they were benefitting from the drugs (even placebo), when that certainly was not the case.

In the hospital, however, the staff motivations are not hard to understand. Physicians routinely explain their medical thinking in their medical records. Even in the medical records of a distinguished teaching hospital, not one of 331 charts of patients receiving sleeping pills had a proper record of why the pill was given. The motivations of physicians to give patients sleeping pills have not been studied extensively, but there is some interesting evidence. It has been the same in the hospitals where I taught. It is safe to assume that there often was no good medical justification.

Other Risks of Sleeping Pills.

2.D. Lollipops, not sleeping pills.

Physicians routinely write sleeping pill orders in the hospital, because they hate for nurses to call at night and wake the doctor up to get a sleeping pill order. As a medical student, I was instructed that if I wanted to sleep at night, I had better routinely prescribe a sleeping pill for every patient. When I was a medical student, I learned that nurses like to keep their patients quiet for the night. If we train young doctors this way in hospitals, the habits will carry over to outpatient practice. Everyone has heard the stories of nurses awakening patients to give them sleeping pills.

We find from the FDA records of this study that there were more accidents and more cancers among those receiving eszopiclone. I must say that I have trouble believing that is correct. This same study reported more severe adverse effects with eszopiclone than with placebo. I admit there might be at least one exception, a study of eszopiclone, which claimed that people given the drug reported better function in the long term. Those subjective reports did not seem consistent with the company’s own objective studies of how eszopiclone impairs performance. A new study by a different manufacturer showed conclusively that eszopiclone can impair many kinds of performance on the morning after taking a bedtime dose, even in healthy young adults.

Some years ago, I was privileged to participate with a group of sleep experts from different medical schools in a study sponsored by Hoffmann-La Roche, the makers of Dalmane (flurazepam). The short-acting drug tested was midazolam, which is sold as a hypnotic in Europe, though in the U.S. Many experiments on hypnotic effects on performance had used young healthy volunteers, who had little room for improvement in their sleep. We thought that healthy volunteers might benefit less than insomniacs who really had disturbed sleep. Therefore, we recruited a group of chronic insomniacs who said they had had insomnia and had taken benzodiazepines successfully for an average of over 13 years. Once withdrawn from whatever they had been taking, they were studied for two baseline nights while receiving a placebo pill. Moreover, we selected volunteers in whom we could verify with EEG-sleep recording that their sleep really was disturbed at night, and then we withdrew these people from their sleeping pills for at least 4 weeks. Perhaps the people who benefit most might be a special group. Then, the volunteers were randomly assigned to receive Dalmane, to receive midazolam, or to continue receiving inactive placebo pills. it is marketed only as a short-acting anesthetic. Concerned about the impairments of driving and other performance caused by Dalmane, the manufacturer wanted to see if a very-short-acting benzodiazepine would improve performance.

People become habituated to these drugs because they experience such anxiety and poor sleep, whenever they try to stop. The manufacturers now admit that both zolpidem (Ambien) and eszopiclone (Lunesta) cause withdrawal insomnia on the night after you stop the pill. If they stayed off the drug for a few days, they might sleep just as well without the medication. Anxiety may also occur as a withdrawal symptom.

A ling study. 2.B.

Ambien depression