Meprobamate and the benzodiazepines have frequently been used as central muscle relaxants, though evidence for general efficacy without accompanying sedation is lacking. A possible exception is diazepam, which has useful relaxant effects in skeletal muscle spasticity of central origin (see Chapter 27).
Psychiatric uses of benzodiazepines other than treatment of anxiety states include the initial management of mania and the control of drug-induced hyperexcitability states (eg, phencyclidine intoxication). Sedative-hypnotics are also used occasionally as diagnostic aids in neurology and psychiatry.
Many of the common adverse effects of sedative-hypnotics result from dose-related depression of the CNS. Relatively low doses may lead to drowsiness, impaired judgment, and diminished motor skills, sometimes with a significant impact on driving ability, job performance, and personal relationships. Sleep driving and other somnambulistic behavior with no memory of the event have occurred with the sedative-hypnotic drugs used in sleep disorders, prompting the FDA in 2007 to issue warnings of this potential hazard. Benzodiazepines may cause a significant dose-related anterograde amnesia; they can significantly impair ability to learn new information, particularly that involving effortful cognitive processes, while leaving the retrieval of previously learned information intact. This effect is utilized for uncomfortable clinical procedures, eg, endoscopy, because the patient is able to cooperate during the procedure but amnesic regarding it afterward. The criminal use of benzodiazepines in cases of “date rape” is based on their dose-dependent amnestic effects. Hangover effects are not uncommon following use of hypnotic drugs with long elimination half-lives. Because elderly patients are more sensitive to the effects of sedative-hypnotics, doses approximately half of those used in younger adults are safer and usually as effective. The most common reversible cause of confusional states in the elderly is overuse of sedative-hypnotics. At higher doses, toxicity may present as lethargy or a state of exhaustion or, alternatively, as gross symptoms equivalent to those of ethanol intoxication. The physician should be aware of variability among patients in terms of doses causing adverse effects. An increased sensitivity to sedative-hypnotics is more common in patients with cardiovascular disease, respiratory disease, or hepatic impairment and in older patients. Sedative-hypnotics can exacerbate breathing problems in patients with chronic pulmonary disease and in those with symptomatic sleep apnea.
Sedative-hypnotics are the drugs most frequently involved in deliberate overdoses, in part because of their general availability as very commonly prescribed pharmacologic agents. The benzodiazepines are considered to be safer drugs in this respect, since they have flatter dose-response curves. Epidemiologic studies on the incidence of drug-related deaths support this general assumption—eg, 0.3 deaths per million tablets of diazepam prescribed versus 11.6 deaths per million capsules of secobarbital in one study. Alprazolam is purportedly more toxic in overdose than other benzodiazepines. Of course, many factors other than the specific sedative-hypnotic could influence such data—particularly the presence of other CNS depressants, including ethanol. In fact, most serious cases of drug overdosage, intentional or accidental, do involve polypharmacy; and when combinations of agents are taken, the practical safety of benzodiazepines may be less than the foregoing would imply.