CLINICAL PHARMACOLOGY OF SEDATIVE HYPNOTICS
TREATMENT OF ANXIETY STATES
The psychological, behavioral, and physiological responses that characterize anxiety can take many forms. Typically, the psychic awareness of anxiety is accompanied by enhanced vigilance, motor tension, and autonomic hyperactivity. Anxiety is often secondary to organic disease states—acute myocardial infarction, angina pectoris, gastrointestinal ulcers, etc—which themselves require specific therapy. Another class of secondary anxiety states (situa-tional anxiety) results from circumstances that may have to be dealt with only once or a few times, including anticipation of frightening medical or dental procedures and family illness or other stressful event. Even though situational anxiety tends to be self-limiting, the short-term use of sedative-hypnotics may be appropriate for the treatment of this and certain disease-associated anxiety states. Similarly, the use of a sedative-hypnotic as pre-medication prior to surgery or some unpleasant medical procedure is rational and proper (Table 22–2).
Excessive or unreasonable anxiety about life circumstances (generalized anxiety disorder, GAD), panic disorders, and agora-phobia are also amenable to drug therapy, sometimes in conjunc-tion with psychotherapy. The benzodiazepines continue to be used for the management of acute anxiety states and for rapid control of panic attacks. They are also used, though much less commonly than in the past, in the long-term management of GAD and panic disorders. Anxiety symptoms may be relieved by many benzodiaz-epines, but it is not always easy to demonstrate the superiority of one drug over another. Alprazolam has been used in the treatment of panic disorders and agoraphobia and appears to be more selec-tive in these conditions than other benzodiazepines. The choice of benzodiazepines for the treatment of anxiety is based on several sound pharmacologic principles: (1) a rapid onset of action; (2) a relatively high therapeutic index (see drug B in Figure 22–1), plus availability of flumazenil for treatment of overdose; (3) a low risk of drug interactions based on liver enzyme induction; and (4) minimal effects on cardiovascular or autonomic functions.
Disadvantages of the benzodiazepines include the risk of dependence, depression of central nervous system functions, and amnestic effects. In addition, the benzodiazepines exert additive central nervous system depression when administered with other drugs, including ethanol. The patient should be warned of this possibility to avoid impairment of performance of any task requir-ing mental alertness and motor coordination. In the treatment of generalized anxiety disorders and certain phobias, newer antide-pressants, including selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), are now considered by many authorities to be drugs of first choice . However, these agents have a slow onset of action and thus, limited effectiveness in acute anxiety states.
Sedative-hypnotics should be used with appropriate caution so as to minimize adverse effects. A dose should be prescribed that does not impair mentation or motor functions during waking hours. Some patients may tolerate the drug better if most of the daily dose is given at bedtime, with smaller doses during the day. Prescriptions should be written for short periods, since there is little justification for long-term therapy (defined as use of thera-peutic doses for 2 months or longer). The physician should make an effort to assess the efficacy of therapy from the patient’s subjec-tive responses. Combinations of antianxiety agents should be avoided, and people taking sedatives should be cautioned about the consumption of alcohol and the concurrent use of over-the-counter medications containing antihistaminic or anticholinergic drugs.