Clinical Textbook of Addictive Disorders 3rd ed - R. Frances, S. Miller, A. Mack (Guilford, 2005) WW

10. Sedatives/Hypnotics and Benzodiazepines 225ties of these medicines resembled the barbiturates. They produced profoundCNS depression, with little or no analgesia. Their therapeutic index was lowand their abuse potential was high, similar to the barbiturates. Chloral hydrate(Noctec), ethchlorvynol (Placidyl), ethinamate (Valmid), glutethimide(Doriden), meprobamate (Miltown, Equanil), methyprylon (Noludar), andparaldehyde (Paral) belong in this class of seldom-used medicines that do nothave a useful place in contemporary medical practice.Despite the continued widespread use of antihistamines to treat insomnia,the Food and Drug Administration (FDA), noting the prominent sedativeside effects encountered in the administration of antihistamines (includingdoxylamine, diphenhydramine, and pyrilamine), concluded that theantihistamines are not consistently effective in the treatment of sleep disorders.Tolerance rapidly develops to the sedating effects of these medicines,and the antihistamines can produce paradoxical stimulation. In addition, theantihistamine doses currently approved for the treatment of allergies are inadequateto induce sleep. Antihistamines used to treat sleep disorders can producedaytime sedation because of their relatively long half-lives (Charney etal., 2001).The use of sedating antidepressants such as Desyrel (trazodone) and Elavil(amitriptyline) to treat insomnia at dose levels lower than are effective for thetreatment of depression, such as the use of sedating antihistamines for this indication,is clinically problematic, since these agents may be both less effectiveand more likely to produce undesirable side effects (especially in producing daytimesedation) than the use of benzodiazepines in this indication (Mendelson etal., 2001).BenzodiazepinesThe benzodiazepines were recognized in animal experiments in the 1950s fortheir ability to produce “taming” without apparent sedation. Cats, which areextremely sensitive to even small electrical shocks, were obviously sedatedwhen given enough alcohol or barbiturates to prevent anxious avoidancebehavior of impending shocks. In contrast, when given benzodiazepines, thecats appeared normal in all of their behavior, except that they did not show theexaggerated anticipatory sensitivity to mild electrical shocks that they showedprior to treatment with benzodiazepines.Chlordiazepoxide (Librium), the first benzodiazepine used in clinical practice,was introduced in 1961. More than 3,000 additional benzodiazepines havebeen synthesized, of which about 50 have been used clinically (Baldessarini,2001). Several of the benzodiazepines, including alprazolam (Xanax), diazepam(Valium), lorazepam (Ativan), and clonazepam (Klonopin) are among not onlythe most widely prescribed medicines for anxiety but are also the most frequentlyprescribed medicines worldwide.