Sedative and Sedative-Hypnotic Drugs

Sedatives are drugs that decrease activity and have a calming, relaxing effect. People use these drugs mainly to reduce anxiety. At higher doses, sedatives usually cause sleep. Drugs used mainly to cause sleep are called hypnotics. The difference between sedatives and hypnotics, then, is usually the amount of the dose—lower doses have a calming effect and higher doses cause sleep.

Currently, the most commonly prescribed sedatives are benzodiazepines, such as Valium. These drugs are also known as minor tranquilizers. Before the development of benzodiazepines in the 1950s and 1960s, doctors most often prescribed barbiturates to cause sleep and sedation. Because barbiturates have a high potential for abuse, doctors today rarely prescribe them. The exception is phenobarbital (Luminal), which is still used as a sedative and as an anticonvulsant .

Sedative-hypnotics can produce side effects in some people, especially the elderly and the very young. Elderly patients who need a sedative-hypnotic sometimes take chloral derivatives, which include chloral hydrate. These drugs are less likely to cause restlessness in older patients who suffer from confusion or dementia . They are also relatively safe to give to children for sedation before or after surgery. Chloral derivatives can, however, cause stomach irritation and rashes.

Doctors often recommend antihistamines for patients who need only a mild sedative. Drugs such as diphenhydramine (the sedative ingredient in the over-the-counter medicines Benadryl, Nytol, and Sominex) and hydroxyzine (the prescription drugs Atarax and Vistaril) are safe and do not produce dependence . However, they should not be used together with alcohol. The most common side effect of these medications is dry mouth.

An advance in the development of sedative-hypnotics occurred with the discovery of the non-benzodiazepine drugs zolpidem (Ambien), zopiclone, and zaleplon. These drugs are short-acting hypnotics that produce fewer side effects, such as a hangover effect (remaining sedation after the person stops taking the drug). Patients who take them for insomnia are less likely to have sleep problems again when they stop taking the drugs. This "rebound insomnia" is a common problem with benzodiazepines. These new drugs are also less likely to be abused than many of the other sedative-hypnotics and cause little respiratory depression.

Buspirone (BuSpar) is the only anti-anxiety medication that is not a sedative. It does not produce depressant effects or dependence. As a result, doctors are increasingly prescribing it to treat depression as well as anxiety. Unlike sedative drugs, buspirone does not affect the patient's alertness or motor skills; it does not intensify the effects of alcohol; and it does not produce a withdrawal syndrome.

The Medical Use of Hypnotics

Approximately 10 percent of young adults complain of serious sleep problems. By the age of 70 or older, 30 to 50 percent of adults will have sleep problems. For many, a prescription for a sedative-hypnotic drug is an effective treatment. Sleep problems in adults are of three main types: (1) Having trouble getting to sleep. This type of sleep problem varies little with age. (2) Having trouble staying asleep. This type of sleep problem worsens with age. (3) Waking up very early in the morning. Early-morning wakening is often a symptom of depression.

Because sleep problems occur more frequently in older adults, use of sedative-hypnotic drugs is more common in older age groups. For example, in the United States 2.6 percent of all adults take a benzodiazepine as a sleeping pill during a year. Among the elderly, 16 percent take sedative-hypnotics during a year. Of that 16 percent, 73 percent take the drug regularly for a year or more. Across all age groups, roughly twice as many women as men take sedative-hypnotic drugs. The most commonly prescribed hypnotics include several benzodiazepines: flurazepam (Dalmane), quazepam (Doral), temazepam (Restoril), and triazolam (Halcion). Other hypnotics not related to the benzodiazepines are hydroxyzine (Vistaril), an antihistamine, and chloral hydrate (Noctec).

Some people take sedative-hypnotics only occasionally for specific sleep problems. These problems may be caused by grief, stress over a limited period of time, or long-distance flights. Many more people take them over months and even years to cause nightly sleep. However, medical advice is to use sedative-hypnotics for only about two weeks. Most sedatives are taken by mouth, but some can be taken by injection.

Benzodiazepines. Benzodiazepines remain by far the most frequently used sedative-hypnotic drugs. There are three main concerns about the use of the benzodiazepines as hypnotics: (1) side effects experienced while the patient is taking the drug; (2) the possibility that the patient may become physically and psychologically dependent on or addicted to the drug; and (3) rebound insomnia and withdrawal symptoms when the patient stops taking the drug.

Benzodiazepines can be grouped in three ways according to how long their effects last. Long-acting drugs include flurazepam, diazepam (Valium), and chlordiazepoxide (Librium). Medium-acting drugs include temazepam. Short-acting drugs include triazolam, oxazepam (Serax), and lorazepam (Ativan). All of these drugs have proven effective when used for short periods. Improvements in sleep correspond closely with the actions of each particular drug. For example, temazepam is absorbed into the bloodstream relatively slowly and does not have the effect of helping someone fall asleep more quickly. A person who has trouble falling asleep will have more success with triazolam, which is absorbed quickly.

The Effects of Sedative-Hypnotic Drugs

Very high doses of most sedative-hypnotic drugs produce general anesthesia and can depress, or slow, a person's respiration so much that breathing must be maintained artificially or the person will die. The benzodiazepines are an exception to this. Higher doses of these drugs typically produce sleep and are far less likely to severely depress respiration.

In some people, sedative-hypnotics produce effects opposite to the calming, soothing feelings the drugs usually produce. Instead, these people experience excitement and confusion. This tends to occur more frequently in the very young and in older people.

Each sedative-hypnotic has a minimum dose at which it will produce effects. Doctors may prescribe a dose that is twice as high as the minimum to be effective at solving a patient's sleep problems. Further increases may, however, cause side effects.

Benzodiazepine sedatives have three major side effects:

• cumulative effects: when a person takes a second or third dose before the previous doses have been degraded or destroyed by the body
• additive effects: when a person takes a benzodiazepine together with another sedative or alcohol, causing the effects to be greater than with any single dose alone

• residual effects: when a person continues to experience the effects of a medication after he or she has stopped taking it

Patients taking benzodiazepines may experience drowsiness, reduced speed of reaction and muscle response, and impaired concentration. These effects can impair a person's ability to function. Doctors should caution patients about driving and operating machinery. When a person takes the drug repeatedly, he or she can develop tolerance to these sedative effects.

All benzodiazepines can impair the ability to learn and remember new information. This effect on memory is strongest a few hours after a person takes the drug. Such effects may be greatly reduced by the time the person wakes the next morning. Rarer side effects include loss of inhibitions and aggressive behavior. These have been reported for some benzodiazepines (such as triazolam and flunitrazepam) more than others.

Rebound Insomnia. When a patient takes a benzodiazepine to treat insomnia and then stops taking the drug, the sleep problem may actually be worse than it was before the medication. The size of the dose can determine whether a patient will suffer from rebound insomnia. For this reason, doctors should prescribe the lowest effective dose. They should also warn patients not to take a higher dose to fall asleep more quickly or to have better sleep.

Dependence and Withdrawal

Some argue that rebound insomnia is a sign of physiological dependence on benzodiazepine hypnotics. Others disagree, arguing that dependence occurs only when withdrawal from a drug leads to symptoms other than a return of the original problems.

Psychological dependence on benzodiazepines can develop rather quickly. After only a few weeks, patients who attempt to stop the medication may experience the following:

• restlessness or difficulty settling down to complete a task
• disturbing dreams
• paranoid ideas, including groundless feelings that people do not like you or do not want you to do well, as well as delusions
• feelings of tension or anxiety in the early morning

Withdrawal symptoms following moderate-dose usage may include dizziness, increased sensitivity to light and sound, and muscle cramps. Withdrawal following high-dose usage may result in seizures and delirium.

The withdrawal syndrome for benzodiazepines may appear slowly because these drugs remain in the body for relatively long periods after the user has stopped taking the medication. Withdrawal appears to be most severe in patients who use benzodiazepines that are absorbed rapidly (alprazolam, lorazepam, and triazolam). In patients who abuse both benzodiazepines and alcohol, a delayed benzodiazepine withdrawal syndrome may produce complications as the person undergoes withdrawal from alcohol. Patients who are high-dose abusers of benzodiazepines usually require detoxification at a hospital as an inpatient.

The Abuse of Sedatives and Sedative-Hypnotic Drugs

Abuse of benzodiazepines by themselves is relatively unusual, but it does sometimes occur among users who seek a high from massive amounts of these drugs. Abuse of tranquilizers and sedatives follows the same basic trend in use as that of many other drugs: It peaked in the 1970s, fell from the 1970s until the mid 1990s, and then began to rise again gradually. Among 8th graders, abuse leveled off in 2001; among 10th and 12th graders, abuse continued to rise slightly in 2001. Street dealers sell benzodiazepines at a relatively low cost in most major cities. Some abusers combine benzodiazepines with other drugs to enhance the effects. For example, alcoholics and heroin addicts will at times use benzodiazepines to supplement the supply of their drugs, since the benzodiazepines have similar depressant effects. Many people who abuse sedatives are or have been heavy drinkers. Patients with a history of alcoholism or other drug abuse problems should not be treated with benzodiazepine sedatives on a long-term basis because they are at high risk of abusing benzodiazepines. Overdosing on benzodiazepines is a medical emergency. Signs of overdose include slowed or shallow breathing and low blood pressure causing dizziness, shock, coma, and eventually death.

see also Accidents and Injuries from Drugs; Addiction: Concepts and Definitions; Barbiturates; Benzodiazepine Withdrawal; Benzodiazepines; Drug and Alcohol Use Among the Elderly; Prescription Drug Abuse; Suicide and Substance Abuse.