The type of treatment of the anxious-depression of the aged patient, on the basis of what is reported above, should consider three main variables: the role of anxiety, the primarity or endogenicity of the depression, and the coexistence of somatic disorders. Anxiety, insomnia, and somatizations justify the onset of a secondary depres­sion and may play a preeminent role in the depressive picture. In this instance, anxiety should be treated with anxiolytic agents, first of all of benzodiazepine type, or with low-dose neuroleptics, or as a second choice with beta-adrenergic blockers or valproic acid amide. The choice of one of these agents could be motivated as follows: the use of benzodiazepines appears to be justified especially by the lack of important organic problems (vascular or metabolic brain disorders). It is known that benzodiazepines (BD2) could cause paradoxical effects, such as psychomotor agitation or confusional states, especially in subjects with a marked metabolic impairment in CNS. In other terms, the more impaired the cerebral functions, the easier the onset of paradoxical effects or side effects (confusional states). At any rate, it is necessary to prefer BDZ without active metabolites and with a short or ultra-short half-life (oxazepam, triazolam) without risks of ac cumulation owing to longer half-lives since the marked reduction of liver met­abolic capacity. The new BDZ, so-called antidepressant benzodiazepines such as alprazolam, adinazolam, zometapine (this latter is still in the stage of phase II study) are rather interesting, since they act on the noradrenergic system and exert an an­tidepressant as well as an anxiolytic action. The limit to the use of these agents is that they can activate, in some cases, the anxious somatizations and, therefore, are contraindicated if the degree of somatization is particularly remarkable. Low-dose neuroleptics, such as trifluo­perazine and thioridazine, have no contraindications; but it must be stressed that they could worsen the depression, if it is not secondary to the anxious phenomena, but is elusive, creeping, and masked in its severity (depressive "iceberg").
Beta-adrenergic blockers are particularly indicated in the course of somati­zations, especially at heart level. The limit to their use is that they are of course hypotensive and, therefore, must be used in low doses and, like neuroleptics, could worsen depression. Concerning the use of valproic acid amide, it is widely used in subjects in which treatment with the above mentioned agents is problematic, and, in any rate, it could be combined with one of them, since valproic acid is a metabolic inhibitor and will tend to raise the blood levels of the combined drugs, with the obvious result that the side effects will also increase. In the course of anxiolytic therapy, it is possible that the patient has no more anxiety or somatizations, but the depressive features not only do not disappear, but could even become more evident and severe. This could suggest hidden endogenous depressive elements, probably worsened by the use of a neuroleptic

agent or a beta-blocker. In this case, it is necessary to start proper antidepressant treatment with classical or atypical antidepressants, including new benzodiaze­pines at high dosage. Among tricyclic agents, nortriptyline or clomipramine should be preferred, in view of the contraindications mentioned below, depending on the presence of organic problems. The presence of these physical disorders, particularly worrying (prostatic hypertrophy, glaucoma, cardiovascular disorders), which could be very dangerous, should suggest the use of the second-generation antidepressants with lower anticholinergic and cardiotoxic effects, such as mian­serin, viloxazine, or amineptine. But we must bear in mind that there are age-related kinetic differences (2-4) as shown for some typical and atypical antide­pressants (Figs. 1 to 4). In a study carried out with viloxazine on a mixed depressed population, in terms of age and therapeutic "milieu" (1), the influence of age and therapeutic milieu on plasma levels, clearly emerged, in the sense that the best clinical re­sponse was observed in aged patients treated on an out-patient basis, while this did not occur in younger subjects. This was due to the fact that rooting out elderly subjects (with a slower rate of adaptation) from their own environment was avoided. The finding confirms Millard’s statement (8) that better results in treating depression of various types "would be obtained if the hospital went to the home." In conclusion, for the future a better nosographic arrangement of anxiety and depression of the third age is needed, on the basis not just of the clinical phe­nomenology, but also of neurophysiological, morphological, and pharmacological patterns, trying to point up the biological "rate" present in each case that is an essential criteria for any successful pharmacological approach. Treatment can be problematic owing to the basic functional impairment of various systems, thus the search for compounds effective specifically in the psy-chopathology of aged patients must also take into account greater tolerability than the compounds presently available.

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