Leo Alexander

The inert psychasthenic reaction (anhedonia) as differentiated from classic depression and its response to iproniazid.

The development over the past twenty years of physical treatments with a wide range of effectiveness, due probably to the fact that they all reduced the general excitability of the higher nervous activity of the cortex,’ has tended to blur the outlines of the nosological entities that had been painstakingly drawn during the preceding one hundred years. However, the recent advent of drugs with rather specific effects on symptomatology is forcing us to renew our interest in the finer differentiations of clinical nosology with an eye, perhaps, toward uncovering brain mechanisms that may be specifically influenced by the newer and more highly specialized drugs. The fact that the new drugs relieve specific aspects of symptom formation rather than broader categories of illness has been perceptively stated by Kalinowski.2 Freyhan3 speaks of effects upon specific “target symptoms” as the mode of action of drug therapy. T o this we should like to add the concept of “key symptoms”; if the target symptom also happens to be a key symptom of primary importance in evoking a chain of other reactions that constitute the clinical picture, the entire remainder of the clinical disturbance may be relieved as well, in line with Gantt’s4 concept of autokinesis. Quite apart from its traditional division into manic-depressive, involutional, and neurotic depressions, depression is not a nosologically uniform symptom complex, but may represent strikingly different clinical syndromes that cut across the dividing lines named above. There are depressions in all of these groups that lack the classic symptoms of remorse and self reproach, but instead exhibit inability to experience pleasure *and satisfaction, a joyless inhibited state that Rlyerson5 called anhedonia. Instead of self-reproaches, these patients abound with self-pity. They do not consider themselves wicked, but merely weak and powerless. They are not driven to madness by the furies of remorse like Orestes but, like Job, they wallow in self-pity: “Why does this happen to me, a good man?” These patients are often characterized by profound inertia and psychomotor inhibition. The most severe cases of this type come close to or include Hoch’s6 “benign stupors” and Kleist’s psychomotor depre~sions.~ Rosen and one of us (L.A.),8 in studying the psychological issues that were operative in depressions, found that the impelling issue in this type of case is envy, in contrast to the issue of guilt operative in the classic depressions. In terms of Bibring’s9 narcissistic aims, the dynamic narcissism in these cases is not the need for morn1 goodness or worthiness, but the need for power that appears to be frustrated.

DIFFERENTIAL EFFECTS OF THE NEW “PSYCHOTROPIC” DRUGS

The action of the new tranquilizing drugs-chlorpromazine and reserpineas well as that of other phenothiazine derivates related to chlorpromazine, such as mepazine (Pacatal) and promazine (Sparine), is fundamentally different from electroconvulsive therapy in that these drugs appear to suppress the primary, epinephrine-precipitable, subcortical warning or tension anxiety,l while exerting only an indirect influence on its secondary disorganizing effects, namely, of panic or depression. Gliedman, LaSalle, and Gantt2 found that the tranquilizers reduced or abolished the orienting reflex and thus inhibited the formation of new conditional reflexes. These antiadrenergic drugs probably interfere with the action of serotonin upon the cerebral centers. They achieve their selective effect by specific reduction in the activity of the posterior hypothalamus. The centrencephalic reticular activating system, which mediates arousal, is blocked by small doses of chlorpromazine, but is released by reserpine, as well as by larger doses of chlorpromazine; this release further reinforces the cortical inhibition of the hyp~thalamus.~ The resulting suppression of anxiety and its secondary effects are in inverse proportion to the degree to which important ego functions have been disrupted or paralyzed by an excess of anxiety. Hence, tranquilizing medication, particularly with chlorpromazine, is most effective in the manic state since, as I have pointed out el~ewhere,~ that condition is most directly power-driven toward excitation by tension anxiety and is a state in which important ego functions are relatively preserved. Conversely, for exactly the same reasons and in remarkable accord with the fact that inhibitory cortical processes are more readily extinguishable than are excitatory ones,5 manic psychoses are least readily relieved by electroconvulsive therapy (an extinction type of treatment) unless the treatment is carried to the point of obliterating even the mere perception of warning or tension anxiety. An ancillary but far from insignificant reason for the superb clinical results of chlorpromazine therapy in manics is that these psychoses tend naturally to be of short duration. If, accordingly, the manifestations of the psychosis can be suppressed for the natural duration of the manic episode, the patient can continue to live a reasonably normal life and may even be able to continue to work without experiencing either the social disadvantages of morbidity or the undesirable suppression of cortical functioning produced by electroshock. Depression is at the other end of the scale of effectiveness of the new tranquilizing drugs. Not only are chlorpromazine, reserpine, and related drugs entirely ineffective in most cases of depression, but they are actually contraindicated, since they may aggravate the condition. The reason for their ineffectiveness obviously lies in the fact that, in depression, paralysis of the cortical