The Canadian Journal of Psychiatry

This was a retrospective study in which 50 hospitalized depressed women were rated on 25 items of symptomatology and these items were then subjected to factor analysis. Five factors were extracted and attention was focused on the first factor. Items which loaded heavily on this factor included insomnia, especially in the middle of the night and early morning, severity of depressed mood and global severity of illness, retardation, guilt and self-reproach, weight loss, delusional symptoms, visceral symptoms, agitation, and loss of interest. The symptoms and signs which loaded heavily thus fit the classical pattern of endogenous depression. The patients were scored on this factor and these factor scores were then correlated with the patients' ratings on premorbid personality, personal history, and evidence of apparent precipitant, items which were independent of the factor analysis. The factor scores were found to correlate negatively with presence of apparent precipitants and negatively with hysterical character. The distribution curve of factor scores suggested a distinct group of patients in a hump at the end of the curve. Corresponding factors in other studies were shown to approximately reproduce the items loading on this factor. When applied to our patients these factors produced factor scores which correlated highly with our factor scores and selected the patients in substantially the same distribution.

We are currently engaged in investigating the characteristics of our endogenous group of patients to determine how they differ from the remainder of our population. We expect the current studies to lead to a prospective study in which we will take up problems of rater reliability and study a larger patient sample.

The main thesis of this presentation is the contention that in the clinical assessment of a depressed patient one must use not only the relatively coarse criteria of changes of mood and affect, psychomotor retardation, diurnal variation, sleep disturbance, etc. but also the finer criteria centering around his object relationships (2). These latter can be seen in the doctor/patient relationship even in the first interview. A most crucial criterion revolves around how, and to what extent, the patient reaches out towards, or withdraws from, the doctor. The use of these criteria clarifies the indications and contraindications for psychoanalysis, psychotherapy, drugs or E.C.T. in the depressed patient.

1) It is assumed that depression, whether in the normal or the mentally ill, results from insufficient positive reinforcement or reward. The depressed patient, however, despairs even if the environment supplies a normal amount of rewarding stimulation. This failure of rewarding stimulation to exert its usual energizing effect is attributed, at least in some types of depression, to a biochemical defect in the hypothalamic reward mechanism.

2) Self-stimulation studies made it possible to investigate the pharmacology of the reward mechanism in experimental animals. It was concluded that the reward mechanism is directly or indirectly activated by a catecholamine, probably norepinephrine, on the following evidence:

a) Chemical analyses show that self-stimulation structures are unusually rich in norepinephrine.

b) Self-stimulation is selectively inhibited by chlorpromazine, which antagonizes norepinephrine centrally, and by reserpine, which depletes the brain of norepinephrine.

c) Self-stimulation is selectively facilitated by amphetamine, which resembles norepinephrine closely in chemical structure, and which appears to produce its stimulating effect by liberating norepinephrine from stores in the reward system. Other potent releasers of norepinephrine, like α-methyl-meta-tyrosine and tetrabenazine (in combination with a mono-amine oxidase inhibitor) selectively facilitate self-stimulation too.

3) It is therefore suggested, on this and other evidence, that at least some types of depression result from an insufficient synthesis or utilization of norepinephrine in the reward system, and that antidepressive drugs probably act by the following mechanisms:

a) Monoamine oxidase inhibitors relieve depression by building up levels of norepinephrine in the reward system.

b) Imipramine and related drugs relieve depression by elevating the level of free norepinephrine in the reward system, probably by blocking its uptake into storage sites.

c) Amphetamine sometimes provides temporary relief from depression by releasing norepinephrine from stores in the reward system.

The metabolism of infused H³-norepinephrine was studied in twenty psychiatric patients with depression. A difference was found in the metabolism in those patients classified as manic-depressive in that they tended to have a definite increase in the urine in the proportion of those metabolites which retain the amine group as compared to the metabolites which had undergone oxidative deamination (N/O ratio). The main amine metabolite was normetanephrine while the main oxidized metabolite was vanillomandelic acid. Patients diagnosed as reactive depression also tended to have an elevated N/O ratio, but to a lesser degree than the manic-depressives. Those patients with involutional psychosis or schizophrenia with depression did not differ from the normals in the amine metabolism.

E.C.T. appears to be especially effective in those patients with an abnormal amine pattern and it also corrects the disturbance in the metabolism. Chlorpromazine, imipramine, amitriptyline and chlordiazepoxide cause a marked change in the metabolic pattern of norepinephrine.

Evidence is cited which suggests that the altered norepinephrine metabolism may result in an elevation of normetanephrine at synaptic sites which could antagonize the action of sympathetically-released norepinephrine.

Familiarity with certain physiologic and biochemical reactions and factors of succinylcholine (SCh) in man is helpful in safely administering SCh in convulsive therapy and anesthesiology. These reactions and factors are:

1) the natural variations in the titer of butyrylcholinesterase (BChE) in the plasma,

2) the interactions between SCh with BChE,

3) the action of SCh in the congenital absence of BChE,

4) understanding of the mechanism of transmission of the nerve impulse,

5) the action of succinylcholine at the motor end plate.

Discussion of the above reactions and factors are presented. Two physiologic tests are described. These are the 3 mg SCh test dose and the tendon reflex test. The proper application of these two tests make possible the safest use of succinylcholine in convulsive therapy, as well as in other fields of medicine.

The BHPT is an inexpensive, easily administered rating instrument for the severity of depressive illnesses. It was administered to 31 patients diagnosed as suffering from one of the depressive group of illnesses, and to 36 non-depressed patients as controls. Weighted scores gave excellent discriminations between the two classes and re-testing measured recovery from depression. The BHPT is thus an excellent rating instrument, useful in clinical and psychopharmacological research and in the psychiatric training programs.

A conditional reflex test procedure was described which enabled us to reveal and measure the characteristic differences among neurotic, endogenous and schizophrenic depressions. The differences found among the depressive groups were expressed in conditional and unconditional reflex variables. The revealed changes direct attention to the possible pathophysiological basis of the different depressive conditions. This is suggested by the behavioural conditioning method but can only be proven through neurophysiological experiments.

Based on the early reports of the successful treatment of depressive states with chlorpromazine, 47 voluntarily hospitalized psychiatric patients referred for drug therapy, were randomly assigned to one of three treatment regimens. Sixteen depressive patients received imipramine, 11 placebo and 20 a combination of chlorpromazine and procyclidine in a six-week, fixed dosage schedule.

On clinical behavioural ratings, both the chlorpromazine-procyclidine combination and imipramine had significantly better therapeutic results than placebo.

These observations are consistent with earlier reports that the treatment of depressive disorders with chlorpromazine may be enhanced by the addition of an antiparkinsonian anticholinergic agent. It appears clear that agitated depressions may be effectively treated with chlorpromazine-procyclidine. Further data is required to evaluate this treatment for retarded depressions.

The reports and clinical experience cited illustrate the physiological withdrawal reaction which follows abrupt imipramine withdrawal. Many such reactions have probably gone unreported or have been misinterpreted as incipient exacerbations of the process under treatment.

It is suggested that the patient reported here meets the W.H.O. criteria of a true addiction (31).

These findings are discussed in terms of life situation and personality predisposition contributing to development of addiction in this patient at this time. He was in a heightened state of anxious oral dependency and wished to make drug therapy almost a way of life.

The following conclusions are drawn:

1) A drug's specific psychopharmacologic effect cannot be considered without reference to the emotional significance of drugs to the psychiatric patient, i.e. to each patient's characteristic way of responding to the drug experience.

2) Withdrawal phenomena may interfere with the evaluation of change due to treatment, or may seem to produce a clinically worse patient. This possibility should be considered when a trial without drugs produces symptoms like those which led to treatment.

3) Imipramine and most psychotropic drugs should be withdrawn gradually, especially following prolonged treatment, and in addicted patients. If abstinence symptoms develop, the dosage should be increased and then gradually withdrawn again over a longer period.

4) The imipramine withdrawal syndrome appears to be non-specific and morphine-like. This suggests the speculation that imipramine belongs to the group of physiological C.N.S. ‘depressants’.

A comparative double-blind study of two antidepressant drugs, opipramol and amitriptyline, had been undertaken in neurotic and endogenous depressions. It was to be carried out simultaneously in a well-staffed university clinic and in an understaffed mental hospital. The depression rating scale used was the one constructed by Wechsler et al. Criteria to differentiate both entities were those described by Kiloh and Garside. It was hoped; 1) to compare the efficacy of both drugs; 2) to compare differences in milieu in regard to the two types of depression and the drugs used; 3) to test the hypothesis, by means of comparing scores on the DRS, that there exists a difference between neurotic and endogenous depressions.

The trial could not be completed because it was very difficult to find neurotic depressions at the state hospital and endogenous depressions at the university clinic. Although the results could not be compared in terms of both institutions and no conclusion could be drawn as to the efficacy of either drugs in neurotic depressions because of too small a sample, it was nevertheless shown that amitriptyline was significantly superior to opipramol in endogenous depressions.

Some methodological flaws of the present study were pointed out, namely, the lack of placebo in the neurotic group, the drawback of a flexible posology and the short observation period (4 weeks). Explanations were propounded to explicate the sampling difference between the two psychiatric institutions.

1) The specific delusion of the eternity of the depressed state presented by psychotic depressed patients in all aspects of their behaviour and thought during their illness, is described and discussed. It consists of the conviction that their depressed state will never end and will continue for an eternity.

2) The hopelessness and helplessness of such patients are directly linked with this delusion (cf. text).

3) The findings of the author, based on psychoanalytically-oriented psychotherapy and psychoanalysis differ from those presented in the existentialist literature (cf. text). Time is neither regularly ‘speeded up’ nor ‘slowed down’, ‘stagnant’ nor ‘dammed up’, nor is the ‘future blocked’ as reported by the existentialist phenomenologists. Rather, patients perceive their future in the deluded conviction that it is an unending depression that will continue unabated forever or for eternity.

4) The author considers the nature of this delusion. For him, the delusion of the permanence of the depressed state results from a marked regression to fixations in the earliest oral phase, in which the passage of time can only be measured by changes in the biological rhythms of the organ system denoting such change. Thus a state continues ‘forever’ until it is succeeded by a new organic state of function, e.g. sleep to wakefulness, feeding to satiation and very rapid sleep, etc. (cf. text). This regression explains the nature and form of the cathexis present in the patient's depressed state. Helplessness is felt to be a marked regression of aggressive cathexis to a late oral (pre-anal) stage—one prior to the development of sphincter control and mastery (cf. text).

5) The author also discusses some aspects of technique in using the above concepts in psychotherapy and psycho-analysis, of this aspect of their illness, of such patients (cf. text).

6) The patients' poor motivation to continue on-going psychotherapy once out of the depressed state, and the specific psychodynamic reasons for this, are discussed (cf. text).

The opinion that depression is a reaction to a loss is supported. It is suggested that the loss is that of an inflated idealized version of the self which is a necessary aspect of living to the neurotic in order to derive pride, satisfaction and self-esteem. Self-idealization is a process which begins early in childhood in response to basic anxiety and develops on the level of magical, fantasied, wishful thinking. When events of life pierce the armour of self-glorification, the individual falls like a deflated balloon into the depth of despair and self-hate, the clinical expression of which is depression. Depression, through its slowing down of living processes, helps to isolate the individual from his environment and therefore permits the psychic apparatus to devote its energies to reinflate the balloon and restore the premorbid idealized image. Certain therapeutic implications inherent in this point of view are discussed. No claim is made that the suggested dynamic point of view is the exclusive dynamics of depression or that it obtains in all types of depressions.

Here reported are six patients with depression of late life and brain syndromes, who responded to an eclectic approach of tranquillizers, antidepressants and psychotherapy, using concepts from Gutheil, Rado and Arieti. Environmental manipulation, use of proprioceptive action self, and discussion of the origins of each depressive episode often helped to ameliorate symptoms and improve the clinical picture. Psychotherapy with these patients may necessarily involve newer but accepted techniques used in specific but different ways.

This paper has attempted to differentiate the stages of adaptive and regressive reactions to loss in the aged. Central to this study is the hypothesis that depletion is a distinct and separate entity in a chain of psychological responses—that is beyond depression.

A study of the general reactions to loss reveal three basic patterns of behaviour: mourning (and its somatic equivalent), neurotic depression, and melancholia, in order of severity. The ability to cope with loss is seen to be determined, in part, by the individual's capacity to resolve ambivalences, to tolerate depression and the ability to relate to whole objects. If reparation by projective identification is not possible, depression merges into melancholia. The pattern of reaction to loss begins early in life, largely determined by the child's separation and reunion experiences with his mother, and continues as a ‘defensive style’ throughout life.

The problems of object loss and depression are intensified in old age when the individual is simultaneously coping with real losses of self (body ego) and decreasing stimulation from external objects. Even in the best of circumstances, the reality reinforcement of the ageing process may exacerbate exhaustion of the positive forces in the nuclear self and, if some restitutive action or substitute object relationships for emotional refuelling are not possible, regression will occur. Individuals of melancholic disposition are particularly vulnerable because they are relatively incapable of neutralizing aggression.

Ageing offers an ideal opportunity to study the breakdown of defences and defusion of instincts as the lines of growth are reversed. Depletion reactions which have generally been subsumed under the diagnosis of depression and/or senility are seen as distinctly differentiated and observable precursors to the ego's fragmentation, disintegration and abandonment of an ‘objectless’ world.