Benzodiazepines are central nervous system depressants that are usually prescribed to help individuals cope with severe anxiety disorders and may also be used on a short-term basis to treat insomnia. They are also sometimes called tranquilizers. The Controlled Substances Act classifies benzodiazepines as depressants, and they are Schedule IV drugs. These medications may be offered orally or by injection.

Some benzodiazepines, particularly chlordiazepoxide hydrochloride (Librium), clorazepate (Tranxene), Diazepam (Valium), and oxazepam (Serax), are used to help individuals who are undergoing withdrawal from alcohol or drugs. Some benzodiazepines, such as Alprazolam (Xanax) and clonazepam (Klonopin), are used to treat panic disorder. In some cases, benzodiazepines such as clonazepam, diazepam, and lorazepam (Ativan) are used to treat seizure disorders, such as epilepsy.

Note that benzodiazepines should not be taken with alcohol or with any other sedating drugs because the combination of these substances could become dangerous or even fatal to the consumer.

Leo Sternbach, a Polish chemist who fled to the United States in 1941 during the Nazi occupation, is credited with discovering the formulation for the first two benzodiazepine medications, Valium and Librium, for Roche, a global pharmaceutical company. These medications were first marketed to the public in the 1960s, Librium in 1960 and diazepam in 1963. These medications were extremely popular around the world during the 1960s and 1970s. However, concern about the potentially addictive qualities of benzodiazepines when the drugs were abused eventually developed.

Benzodiazepines are cross-tolerant with alcohol; that means that the chronic use of alcohol can create a greater tolerance for benzodiazepines, and vice versa. In addition, this cross-tolerance is the reason that benzodiazepines are used in the treatment of acute alcohol withdrawal, as carefully chosen doses of benzodiazepines in a tapering schedule can treat or prevent severe alcohol withdrawal symptoms. The withdrawal from an addiction to benzodiazepines is extremely similar to alcohol withdrawal, and it can also be life-threatening.

According to the National Survey on Drug Use and Health, in 2004, 11.2 percent of young adults ages 18-25 used benzodiazepines illegally, as with prescription drug abuse. The single most commonly abused benzodiazepine was diazepam (Valium), and 6.1 percent of individuals of all ages had ever abused Valium in 2004. Another commonly prescribed benzodiazepine, alprozalam (Xanax), was also a drug of abuse.

Other benzodiazepine drugs are abused, especially among abusers of heroin and cocaine, who usually use benzodiazepines to counteract the side effects of the use of heroin or cocaine.

There are about 15 brand names of benzodiazepines that are prescribed in the United States, according to the Drug Enforcement Administration.

Signs of dependence on benzodiazepines include the following:

- a strong desire or need to continue taking the medicine

- a need to increase the dose of the medication to receive the same effects (physical tolerance)

- withdrawal effects (such as irritability, nervousness, insomnia, abdominal cramps, and/or shaking) if the drug is not taken

Individuals who are dependent on a benzodiazepine should be tapered off the drug under medical supervision. Stopping the drug immediately could lead to serious side effects, such as seizures or delirium tremens.

In one study reported in the Archives of Internal Medicine in 1999, researchers tapered the subjects off benzodiazepines, testing the efficacy of melatonin supplements to cope with problems of insomnia. The researchers found that of the 24 elderly patients who received controlled-release melatonin and discontinued benzodiazepines, 19 reported good sleep quality with melatonin.

There are both short- and long-acting benzodiazepines,and benzodiazepines with rapid and slow onset of action. Short-acting benzodiazepines have a short half-life: that is, the body breaks them down rapidly and clears them from the system. They are often prescribed to treat insomnia or for shortterm acute use, such as in panic attacks or fear of flying.

Benzodiazepines that are used to treat insomnia include estazolam (ProSom), temazepam (Restoril), and triazolam (Halcion). Another short-acting benzodiazepine is midazolam (Versed), a drug that is used primarily for surgical sedation. Alprazolam (Xanax), a short-acting drug with a half-life of approximately 2.5 hours, can, however, be a longacting drug in a preparation that allows the medication to dissolve more slowly.

Benzodiazepines that have a rapid onset include alprazolam and diazepam. These drugs are rapidly absorbed into the system and reach peak blood levels quickly. In the special case of diazepam, it may be viewed as both a long- and a short-acting medication because of its rapid absorption into body fat. After several weeks of use, however, the amount of diazepam in the body fat reaches equilibrium with the amount in the bloodstream. This means that in the initial weeks of using diazepam, the drug appears to "wear off" within two to four hours, but after reaching equilibrium, it can last for 12 to 24 hours. In individuals who have decreased liver function, the half-life of diazepam can be upward of 100 hours.

Some benzodiazepines are long-acting drugs, and they can be used to treat insomnia among patients who also have daytime anxiety. Examples of long-acting benzodiazepines include Tranxene, diazepam, halazepam (Paxipam), Ativan, prazepam (Centrax), and quazepam (Doral). Some longeracting benzodiazepines, such as Klonopin, Valium, and Tranxene, are used as antiseizure drugs.

A particular concern in treatment with long-acting benzodiazepines is that withdrawal can occur days after abrupt ceasing of use of the medication, and misdiagnosis and incorrect treatment can result. An initial false sense of security can also be created as individuals taking the drug believe that they were able to stop the medication without difficulty, only to have withdrawal symptoms days later.

The effects of benzodiazepines are analogous to alcohol effects. Thus, benzodiazepines can cause drowsiness, slowed reaction times, poor judgment, and decreased impulse control. In higher doses, significant intoxication can occur, with clumsiness, amnesiac episodes (blackouts), and confusion. The excessive use and abuse of benzodiazepines can lead to withdrawal symptoms up to and including delirium tremens, as is also seen with the excessive chronic use of alcohol.

There are several central nervous system depressant drugs that are similar to benzodiazepine and, as are benzodiazepines, used over the short term to treat insomnia. These drugs include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta). They are Schedule IV drugs.

References:

1)         Garfinkel, Doron, M.D., et al. "Facilitation of Benzodiazepine Discontinuation by Melatonin." Archives of Internal Medicine 159 (November 8, 1999): 2,456-2,460.

2)         Joseph, Donald E., et al., eds. Drugs of Abuse. Washington, D.C.: U.S. Department of Justice. 2005.

3)         Longo, Lance P., M.D., and Brian Johnson, M.D. "Addiction: Part I, Benzodiazepines--Side Effects, Abuse Risk and Alternatives." American Family Physician 61 (2000): 2,121-2,128.

4)         Substance Abuse and Mental Health Services Administration. Results from the 2004 National Survey on Drug Use and Health: National Findings. Rockville, Md.: U.S. Department of Health and Human Services, September 2005.

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