As artfully summarized by Goodwin1 and vividly described by Sternbach himself,2 the benzodiazepines have had a remarkable success story. In 1957, within months of Sternbach's synthesis of Ro 5-0690, Randall discovered that this substance (later designated chlordiazepoxide) had sedative, muscle relaxant, anticonvulsant, and taming effects in experimental animals. Its effects were superior to those of meprobamate, the existing "gold standard," and were accomplished with less toxicity and other untoward effects. Also, chlordiazepoxide lacked the autonomic effects of other available "tranquilizers" such as reserpine and chlorpromazine. Trials in humans were equally positive, and in 1960, only three years after synthesis, the drug was released for use by the Food and Drug Administration. By 1967, only 10 years after its discovery, chlordiazepoxide was the most prescribed drug in the United States. In 1969 this distinction was usurped by its benzodiazepine sibling, diazepam.
Now, some 36 years later, the benzodiazepines remain among the most commonly used drugs worldwide. They are prescribed for a variety of wellestablished purposes: as anxiolytics, sedatives, hypnotics, muscle relaxants, anticonvulsants, and in managing withdrawal from other sedative-hypnotics. Yet, both the medical profession and society show ambivalence toward benzodiazepines. Some suggest they be avoided whenever possible.
In virtually every monograph or special journal issue devoted to benzodiazepines, there is at least one section devoted to risks of adverse effects and potential for abuse. A recent American Psychiatric Association monograph is titled Benzodiazepines in Clinical Practice: Risks and Benefits.3 The APA has published a task force report devoted solely to negative aspects of benzodiazepines: Benzodiazepine Dependence, Toxicity, and Abuse.4
Not discounting the well-considered risks documented in these texts, benzodiazepines have had a favorable safety record when compared with alternative sedative-hypnotic substances including alcohol, bromide, chloral hydrate, barbiturates, meprobamate. glutethimide. methyprylon, and methaqualone. Benzodiazepines, when taken alone, are not lethal in overdoses. They rarely serve as a sole drug of abuse. Abstinence states are manageable, although caution must be exercised when withdrawing patients from large doses or from certain shortacting benzodiazepines such as alprazolam.
Various antihistamine, antipsychotic, and antidepressant drugs have been suggested as alternatives. Yet, the effects of such drugs do not duplicate the therapeutic profile of the benzodiazepines, and they are also associated with risk of adverse effects. Buspirone is relatively safe, but while anxiolytic, it lacks sedative-hypnotic, muscle relaxant, and anticonvulsant effects, and has a relatively long latency of action. Thus, at present, there are no true substitutes for benzodiazepines. It is the contention of the guest co-editors that, when used appropriately and judiciously, benzodiazepines are safe and effective drugs.
In addition, many clinicians have an overly simplistic view of benzodiazepines. Often, benzodiazepines are thought of solely in terms of their sedative-hypnotic, anxiolytic, muscle relaxant, or anticonvulsant properties. It is assumed that these effects are based on actions on gamma-aminobutyric acid (GABA) receptors. Yet, all benzodiazepines are not created equal. The various benzodiazepines (of which more than 30 are currently marketed in the United States, with others available elsewhere) have varying profiles of actions. Rather than being mediated solely through GABA, there is evidence of a benzodiazepine receptor per se, which may be involved in unique anxiolytic effects apart from sedation. As attested to in several of the articles in this issue, benzodiazepines may also have indirect and direct effects on other neurotransmitter pathways including the serotonergic and dopaminergic systems.
With these considerations in mind, this issue of Psychiatric Annals will review certain uses of benzodiazepines aside from well-known applications in young healthy adults, namely use in obsessive compulsive disorder and Tourette's syndrome; in psychoses (where benzodiazepines may have a variety of applications): and in conditions at the psychiatry-medicine interface. In addition, benzodiazepine use in two special populations (in children and adolescents, and in the elderly) will be considered.
Dr. Preskorn and I. as guest coeditors, would like to acknowledge Charles Wilkinson, MD. formerly of the Psychiatric Annals Editorial Advisory Board, who initiated the idea for this issue. Dr. Wilkinson is since deceased. His continued contributions will be missed. He is remembered fondly as a valued colleague and friend.
1. Goodwin DW. Anxiety. New York. NY: Oxford University Press: 1986:32-45.
2. Sternbach LH. The Benzodiazepine Story. Basel. Switzerland: Editiones Roche: 1980.
3. Roy-Byrne FF. Cowley DS, eds. Benzodiazepines in Clinical Practice: Risks and Benefits. Washington, DC: American Psychiatric Press; 1991.
4. American Psychiatric Association Task Force. Benzodiazepine Dependence, Toxicity, and Abuse. Washington, DC: American Psychiatric Press; 1990.