I should like to discuss briefly a particularly important topic concerning the relationship between depression and anxiety in the elderly. It is well known that these experiences could be interpreted as the expression of the same dysthymic spectrum (dimensionalist view) or as manifestation (mutually distinct) with dif­ferent etiopathogenesis, clinical course, and outcome, which could be occasionally coincident in certain periods of life (dualist view). In the aged patient, anxiety almost invariably accompanies the depressive symptoms. This anxiety could be regarded as a response elicited by stress and conflictuality that the subject un­dergoes because of various reasons, such as changes in life-style, etc. In other words, anxiety can be considered as a sort of aspecific "background noise" in the existential experience of the subject. However, in some cases it could acquire a deeper and more specific value; it becomes a "vital anxiety," as described by Lopez-Ibor (6), with a feature of biologically determined endoge-nicity, which could be only apparently related to a conflict situation. It seems to be coincident with the depressive phenomena itself in terms of pathogenetic biological mechanism, differing from the pure depressive picture only in the phenomenology. This should be a "continuum" of phenomena of the same dysthymic spectrum, and the definition of endothymic anxiety or of anxious thymopathy (7), or endoreactive dysthymia (10) or, again, atypical depression (11) (to be differentiated from the dysthymic disorders and from the adaptation disorders of DSM-III), at least for the disorders of adult age, could stress the peculiarity of this kind of anxiety combined with depression, not in terms of pure occasional phenomenological overlapping, but of pathologically and biologically determined coincidence. In my own experience, anxiety and depression cannot be framed "tout court" in dualistic or dimensionalistic definitions. An important factor is the frequent coexistence in the aged patient of the two aspects in the so-called anxious-de­pressive syndrome. Now, I will try to point out the onset and time course of the symptoms anxiety and depression within this syndrome. In many cases, an anxious state is found initially, which is extremely more frequent than in the younger subject, without "crystallizations" of neurotic type (phobic, obsessive pictures, etc.). It can remain as such or turn to a depressive state, whose severity could qualify in etiopatho-genetic terms, namely, the depressive state following an initial period of anxiety (which could be interpreted in the aged subject as a "trigger" experience) will be deeper the more biologically vulnerable the subject, or the more prone to severe depressive episodes. In some cases, depression seems to be more superficial, with anxiety, insomnia, and the presence of somatizations covering the greater part of the clinical picture with a preserved psychomotor activity. This form of depression can be more related to reactive or situational factors than to endog­enous, biologically determined ones. Only in this instance is it appropriate to talk of an "anxious-depressive state." On the contrary, in the depressive forms of late onset, depression could end up with a total replacement of the initial anxious phenomena. In the reactive forms, we observe the prevalence of excit­ability, restlessness, irritability, whereas in the endogenous forms the psychomotor inhibition is prevalent and suicidal tendencies are present, such as the depressive somatic core or biological symptoms (like circadian mood variations, loss of appetite, loss of weight, reduced libido, insomnia) peculiar to major depression in the adult. Therefore, the evolution of the initial anxiety is different, de­pending on the occurrence of dysthymic or adaptation disorders, or of endoge­nous features. In the former instances, anxiety leads to a reactive depressive state, in the latter, it can be viewed as a phenomenon of a biologically determined dysthymic spectrum, substantially overlapping the major depression of adult subjects. Concerning endogenicity or primarity of depression, it is clear that I am referring to the depressive states occurring in advanced age and not depressive states ap­pearing in elderly subjects suffering also in their adult life from a major affective disorder.

Sixty-two patients (29 men and 33 women; mean age 52.9 ± 9.4 years) par­ticipated in the study. The inclusion criteria were: (a) a diagnosis of Major Af­fective Disorder (Major Depression, Recurrent, n = 32; Bipolar Disorder, n = 30) established on the basis of DSM-III criteria (1); (b) a past history of at least three major depressive episodes; (c) no history of CNS disease, head trauma with loss of consciousness, or alcohol or drug abuse; (d) no evidence of concurrent organic or neurological illnesses; (e) no steroid medication intake for at least 3 months prior to the study. The patients were classified as having a definitely anxious or nonanxious depression whether they had scored respectively more than 9 points or less than 6 points on the Covi anxiety scale (6) during at least three different depressive episodes (Sacchetti et al., this volume). According to this criterion, 29 patients (17 men, 12 women; mean age 55.6 ± 6.7 years) were classified as anxious and 33 (12 men, 21 women; mean age 50.5 ± 10.6 years) as nonanxious. The CT control group was composed of 49 healthy age- and sex-matched subjects who had undergone CT scans for minor accidental head trauma without loss of consciousness (most had been involved in automobile accidents). Inclusion criteria for the controls were the same as items (c), (d), and (e) described above plus no past history or present evidence of psychiatric disorder. Ten to 12 CT slices were obtained for each patient and control. Cerebral ventricular size was measured by manual planimetry on the CT slice that showed the lateral ventricles at their largest and was expressed as Ventricular Brain Ratio (VBR) (24). All the measurements were performed by two raters who were un­aware of the nature of the study and the subjects’ diagnoses. Interrater reliability was determined and found to be high (r = 0.91).

The DSM-HI, published in 1980, provides 25 different diagnostic labels for patients with anxiety; because some anxiety disorders may coexist, a total of 138 different diagnostic combinations is possible. This multiplicity of disorders to­gether with a host of new medications, many of which have "crossover" ability, have served to confuse rather than to clarify treatment protocol for the primary care physician. Some of the confusion may be alleviated by differentiating anxiety or depressive disorders as exogenous or endogenous. Exogenous refers to a normal response to threat, and it usually can be treated successfully with behavior therapy. Only failures in this group need pharmacotherapy. Endogenous disorders, which are metabolic in nature, are both more intense and pervasive and also more physically and psychologically disruptive. Therapeutic intervention is indicated in the ma­jority of such cases. Alprazolam, even within the family of benzodiazepines, is not the only effective pharmacological agent in the treatment of anxiety or anxious depression. And although the benzodiazepines are not the sole family of compounds available to the clinician for these indications, some authorities (8) believe that they are the treatment of first choice. Widespread clinical acceptance has consequently re­sulted in a high comparative scrutiny with other compounds in the treatment of anxiety disorders, mixed anxiety and depressive disorders, and some subtypes of pure depressive disorders. Seldom can one attend a discussion on the phar­macologic treatment of these disorders without some reference to alprazolam’s relative efficacy and side effects. The pharmacokinetic (1) and psychodynamic properties (5) of alprazolam have been extensively studied and reviewed elsewhere. In this chapter, three clinical studies using alprazolam in outpatients that were conducted in whole or part by our organization, a private psychiatric clinic in San Diego, California, will be reviewed.