Descriptions of cases resembling agoraphobia date back thou-sands of years, appearing in the writings of Hippocrates and others. The term agoraphobia was, however, coined less than 150 years ago to describe patients who seemingly experienced unex-pected and situational panic attacks accompanied by anticipatory anxiety and functional incapacitation when walking the streets of their neighborhoods. Freud (1894/1949), whose description of anxiety attacks holds many similarities (but also some notable differences) to contemporary descriptions of panic disorder, was the first to explicate this association. In describing agoraphobia, he specifically mentioned the role of panic, anticipatory anxiety and escape concerns as central to the condition.
The origin of the panic disorder construct as a separate diag-nostic entity was influenced by the work of a number of research-ers but none so much as Donald Klein in the late 1950s and early 1960s. Klein observed that contrary to expectation a subgroup of patients with anxiety neurosis did not improve on chlorpromazine and in some cases became worse. When he gave this subgroup imipramine, a new compound derived from modifications to chlo-rpromazine, marked improvements were observed. Prior to taking imipramine these patients unlike those who were responsive to chlorpromazine had been experiencing rapid rushes of terror, rac-ing hearts and other physical sensations, which prompted them to rush to the nurses station with reports that they were about to die. On the basis of this differential drug response, Klein con-cluded that imipramine was effective against these seemingly spontaneous episodes of panic and, importantly, that these attacks were distinct from other forms of anxiety. He also suggested that agoraphobia was a consequence of spontaneous panic attacks.