Psychopharmacologic treatment of anxiety disorders began with the use of sedative-hypnotics (e.g., bromide salts, alcohol, chlorol hydrate) at the turn of the twentieth century. Barbiturates (e.g., phenobarbital, pentobarbital) were introduced early in the twentieth century but their adverse side effects, including addiction liability and toxic overdose, limited the use of these agents. The development of the benzodiazepines (e.g., chlordiazepoxide, diazepam) in the 1960s as general anxiolytics (separate from the muscle relaxant properties) was a major breakthrough because of the wide effective dose range and the limited adverse side effects. Subsequently, beta-adrenergic receptor antagonists (e.g., propranolol), antihistamines (e.g., hydroxyzine), and anticholinergic agents were used to treat specific cases of anxiety disorders (e.g., speech anxiety, posttraumatic stress disorder [PTSD]). More recently, azapirones (e.g., buspirone) that act via serotonergic antagonism and some dopaminergic antagonism have proven useful for mild forms of generalized anxiety. In the late 1980s, selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine [Prozac], sertraline [Zoloft], paraxetine [Paxil]) were introduced and, in the 1990s, were approved for treatment of specific anxiety disorders (e.g., panic, agoraphobia, PTSD). In addition, tricyclic drugs (e.g., clomipramine, imipramine, amitrip-tyline) and monoamine oxidase inhibitors (MAOIs) (e.g., phenelzine, tranylcypromine) are used in the treatment of some anxiety disorders (e.g., panic, agoraphobia, PTSD).
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