Article by Daly

To understand why people continue taking benzodiazepine hypnotics when experiments show they improve sleep so little and impair performance, it may be helpful to discuss some affects of these drugs on behavior. In experiments where a laboratory rat will receive an unpleasant shock when it presses a lever, an animal given a benzodiazepine will be more likely to press the lever than an animal given placebo. Scientists say that benzodiazepines disinhibit punished behavior, which means that the animals become more likely to hurt themselves or to behave in a way in which they will be hurt. Another way of saying this is that benzodiazepines disinhibit aversive behaviors. There is a human analogy.

In humans, the action of benzodiazepines is to reduce fears of being harmed, which we may call being tranquilized. People very much like this feeling of reduced fear, and there is no doubt that many people like how they feel when taking benzodiazepines. The manufacturers could not sell as many as 100,000,000 benzodiazepine prescriptions in the U.S. yearly if people did not like them. Unfortunately, this tranquilization effect includes the risk of reducing a person healthy fear of self-destructive actions. For example, a person driving 80 mph down the highway approaching a curve ought to slow down for the curve, but taking a benzodiazepine might make the driver less likely to slow down. In some studies, benzodiazepines make people more likely to be aggressive. This blunted fear of harmful behaviors or blunted anxiousness to protect oneself may be one way in which sleeping pills shorten people’s lives.

There is another curious twist to this idea. When we consider that benzodiazepines increase people’s tendency to act in a self-harmful way, it is logical that taking harmful sleeping pills may be one of the harmful behaviors which benzodiazepines tend to increase.

A strange new finding we have obtained with colleagues at Scripps Clinic is that people who take sleeping pills such as eszopiclone, zaleplon, and zolpidem have about a 44% higher risk of developing infections such as sinusitis, pharyngitis, upper respiratory tract infections, influenza, herpes, and so forth. There has been essentially no discussion of this risk in the medical literature, but it is statistically extremely convincing, based on studies which the manufacturers submitted to the FDA and some of their published controlled trials. At present, we do not know why these infections occur, but it does seem that they would be sometimes annoying, sometimes painful, and sometimes frankly dangerous. It is not clear if ramelteon has the same risks, but there is one table in FDA data which suggests that it might. We could not find adequate information concerning the older sleeping pills.

All prescription hypnotics (with the exception of ramelteon) may be physically addicting drugs, and all are sometimes attractive to drug addicts. By addicting, we mean that these drugs have two properties. 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. I frequently see this problem with long-term users of sleeping pills. Second, addicting drugs cause physical withdrawal symptoms when they are stopped abruptly. The withdrawal symptoms of hypnotics such as barbiturates and benzodiazepines are very well known . 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. 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. Severe withdrawal of sleeping pills can produce death. The risk of seizures and death is probably more severe with withdrawal of barbiturates than with benzodiazepines. On the other hand, zolpidem (Ambien) seems less prone to cause withdrawal symptoms than the barbiturates or benzodiazepines. 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.

The addicting properties of hypnotics manifest themselves in several ways. Triazolam (Halcion) is such a short-acting drug that many people used to take bedtime doses which (for the first hour) were much stronger than the initial dose of a drug such as flurazepam or temazepam. But because triazolam disappears from blood largely with 2-3 hours, some people find themselves in triazolam-withdrawal before morning. As a consequence, people taking triazolam may experience increased early awakening . I suspect that zaleplon (Sonata) may be similar to Halcion in this regard, since it scarcely increases total sleep time. The manufacturers have admitted that zolpidem (Ambien) and eszopiclone (Lunesta) can also cause this early awakening. Although the problem may be less with Ambien CR, it is not entirely eliminated.

Next, by wake-up time, the person taking zaleplon or triazolam or zolpidem will certainly be approaching withdrawal. The result, in at least some patients, may be increased tension and anxiety during the day . Such anxiety symptoms might develop somewhat later in the day with temazepam (Restoril) or estazolam (ProSom), because of the longer half-life. I have seen two patients who developed panic attacks for the first time while taking triazolam. After withdrawing from this sleeping pill, the panic attacks of these patients disappeared.

Almost any patient discontinuing any of the short-acting benzodiazepines might experience some sense of anxiety and some withdrawal insomnia after discontinuation. Doctors argue whether the withdrawal syndrome universally leaves patients worse than they would be without the drug, but I suspect it often does. This makes it very difficult for patients to stop using these drugs once they have become habituated to them, and sometimes very long-term usage results, because the patient finds too much difficulty withdrawing.If you listen to the drug companies and many experts who receive research grants from drug manufacturers, they would emphasize that most people who take sleeping pills use them for less than 15 doses in a year and do not become habituated. While this is true, it is likewise true that a small percentage do get into the habit of taking one or more hypnotic pills every night. Because these long-term users take so many pills (365 or more per year), it turns out that most of the hypnotic prescriptions sold go to these chronic users. For example, in our CPSII data, 65% of the sleeping pills reported taken in the past month were taken by people reporting that they took at least 30 doses per month, and these patients reported taking sleeping pills for an average of 5 years. It gives quite a different picture of the sleeping pill industry, when we realize that they are profiting primarily from chronic users who have become habituated or physically addicted to these medicines.