Pharmacologic models of anxiety.

T HE UBIQUITY OF ANXIETY is reflected by the fact that 18% of Americans had an anxiolytic prescribed in 1972, and 6% had more than 2 mo of continuous exposure to a benzodiazepine. Much of the literature on pharmacologic models of anxiety, especially that relating to catecholamines, is quite old and offers a fascinating historical perspective on the modern development of biologic psychiatry. This older literature is limited, however, in several regards, chief among which is that it generally fails to distinguish among the various subtypes of anxiety. Advances in clinical understanding of anxiety as now recognized in DSM-III have led to the characterization of several anxiety states, including panic disorder, generalized anxiety, obsessive compulsive disorder, post traumatic stress disorders, as well as phobic disorders.’ Recent work indicates that, in at least some cases, anxiety may have a significant genetic contribution. ‘v3 Anxiety may also represent the final common pathway for etiologies as diverse as hyperadrenalism, hyperthyroidism, hypoglycemia, hyperdynamic padrenergic state, hypoxia, angina, complex partial seizures, or withdrawal from central nervous system (CNS) depressants. Anxiety may also appear as a part of toxicity to a wide variety of pharmacologic agents, including anticonvulsants, antihistamines, baclofen, cycloserine, disopyramide, indomethacin, nalidixic acid, pentazocine, and quinacrine.4 There are several good reviews of some elements of the literature regarding pharmacologic models of anxiety. Breggin’ and Lader6 offer excellent overviews of catecholamine-induced anxiety, and Pitts and Allen7 have recently reviewed the literature with an emphasis upon lactate’s effects on panic-prone patients. This review will attempt to critique the existent literature of pharmacologically induced anxiety, including more recent data. Anxiety represents a symptom cluster with diverse central and peripheral manifestations, including motor tension, autonomic hyperactivity, apprehension, and hypervigilance. It is a future-oriented emotion in that the anticipation of danger is a cardinal feature. It may appear as a perfectly normal response to current or anticipated environmental stress, may become autonomous, or may represent a final common pathway for diverse biochemical and metabolic insults. Pathologic anxiety is distinguished from normal anxiety on the basis of whether the anxiety bears little relationship to the stressor, is continuous, or whether the anxiety restricts normal activities and functioning. There is a long tradition in psychiatry of attempting to pharmacologically