To many minds there can be but little change in the treatment of depression since Johnson prescribed these remedies in 1776. Indeed the place of chemistry is now prominent, although its application is apparently more important to the patient than its study. It is believed that an enzyme, mono-amine oxidase, found in cerebral tissues, plays a part in the genesis of depression. Amphetamine inhibits the destruction of adrenaline by amine oxidase (McIlwain, 6) and amphetamine is of value in the treatment of mild depression (Guttmann and Sargant, 5). Another substance is 5-hydroxytryptamine, or serotonin, which is said to excite cerebral neurones briefly between its liberation and destruction; it is a cerebral vasoconstrictor and is destroyed rapidly by amine oxidase (McIlwain, 6). Iproniazid (Marsilid) is a drug which inhibits amine oxidase and has been used in the treatment of depression (West and Dally, 10). Its central actions are considered to be similar to those of 5-hydroxytryptamine. Recently, Chessin (3) has described yet another amine oxidase inhibitor, phenelzine, which is the study of this paper.

Beta-phenyl ethyl hydrazine dihydrogen sulphate (phenelzine, “Nardil”) is one of the group of hydrazides being currently advocated for the treatment of depression. It has been claimed that this drug has similar properties to iproniazid but is less toxic (Furst, 1959; Thal, 1959), and uncontrolled clinical trials have produced reports of rapid improvement in 70–80 per cent. of cases (Furst, 1959).

In earlier papers we have shown that ataraxic drugs whose main point of attack lies in the hypothalamic area are able to evoke endocrine effects (1, 2, 3). These are obviously the result of depression of the reticular formation and hypothalamic centres responsible for the anterior pituitary's endocrine activity.

In an earlier investigation (Holland, 1960) the peripheral visual field was examined under three treatment conditions, namely meprobamate (2-methyl-2-n-propyl-1, 3 propanediol dicarbamate), Doriden (glutethimide), and no drug. Results from 24 subjects, each tested three times, indicated that there were significant differences, attributable to the treatments, in both the inner and outer discrimination thresholds and also in the magnitude of the interval of uncertainty between thresholds. In the present experiment it has been thought worth while to examine the visual field for the effects of two other compounds, a stimulant dexamphetamine sulphate (Dexedrine), and a depressant sodium amylobarbitone (Amytal).

The management of mild depression and its concomitant associated symptoms of general debility presents a constant and widespread challenge to psychiatry both in hospital and in general practice. It is inevitable that at some stage resort will be made to drugs. This is a tempting pharmacological field and the level of interest is indicated by the available plethora of alternatives. A recently introduced drug in current use and purported to be of use specifically in this field is Deanol (Deaner) which is the p-acetamidobenzoic acid salt of 2-dimethyl-aminoethanol or Atrol which is the bitartrate of the same base.

There is no discussion in Stevens' (16) or Osgood's (14) textbooks of experimental psychology of the contribution of cortical functions to the production of visual after-images. Woodworth (19) presents a theory of after-images involving the cortex in the first edition of his book. It is not repeated in the second edition. There is, however, a large number of reported studies indicating the importance of cortical functions in the production of after-images (e.g. 1, 3, 6, 9, 11, 12, 13, 15, 17). In view of these studies it was decided to use the afterimage in a further attempt to verify or disprove the drug action hypothesis advanced by Eysenck in a previous paper (2). This hypothesis stated that stimulant drugs increased excitatory potential and decreased inhibitory potential, while depressant drugs decreased excitatory potential and increased inhibitory potential.

There are two stages in the evaluation of a new treatment: the first is to determine if it has any effect at all, and the second is to determine as strictly as possible, the conditions of its applicability. In practice, these two stages overlap considerably, for they are not completely distinct. As soon as some evidence is available that a treatment is effective, attention tends towards ascertaining the precise indications for its use, the evaluation of its effectiveness, its contraindications and complications.

A review of the history and experimental findings relating to the spiral after-effect can be found elsewhere (5) and will not be repeated here. The reliability of the after-effect, the major role played by the cortex in its production and the evidence already obtained that the after-effect is modifiable in accordance with Eysenck's drug action hypothesis (2) indicated it to be a promising test in the investigation into the effects of meprobamate on perception.

A review such as this is not the place, nor has it the space in which to discuss the nature of intelligence. Some conclusion, however, must be reached as to the factors to be considered in estimating any correlation, positive or negative, between level of intelligence and degree of epilepsy.

Fifty-one years have elapsed since the Report of the Royal Commission on the Care and Control of the Feeble-minded was published and paved the way for the Mental Deficiency Act of 1913. Since that time two developments have taken place. On the one hand the administrative procedures for dealing with defectives on the basis of the Act and its amendments have been clearly defined and formalized. On the other there has been a continuous development and expansion of our social and welfare services. These developments, which should have been complementary in their aims, have in fact often proved conflicting in effect, because mental deficiency until very recently was bound to outmoded procedures which were designed to segregate the defective from the community rather than to integrate him with it, and give him the opportunities for re-socialization which our modern welfare services afford. The original belief that a hereditary neuropathic diathesis lay at the root, of most of our social ills and would sooner or later lead to national degeneracy has been replaced by scientific genetic studies, and by medical research into the aetiology of the condition, and the associated problems involved in the training and employability of the defective. Increasing professional and public recognition of the inherent faults of existing mental deficiency legislation led to the setting up of the Royal Commission on the Law Relating to Mental Illness and Mental Deficiency which published its report in May, 1957, and this in its turn has prepared the way for the Mental Health Bill which is at present in the final stages of its passage through Parliament.

Although in the majority of cases E.C.T. is swiftly effective in the treatment of morbid depression there are some who regard it with repugnance, and have long hoped for drugs which would obviate its use. It was that hope which prompted this trial of imipramine (“Tofranil”).

Problem

Elsewhere (3) it has been argued that, when reporting a subject's results on the WISC (5), it is preferable to give them in the form of scores or intelligence quotients on orthogonal factors than as Verbal and Performance I.Q.s since the latter overlap in a rather arbitrary fashion. In this study a similar recommendation is implied when dealing with a subject's results on the WAIS (6) and the problem is to indicate how factor scores on this test can be obtained.

Imipramine hydrochloride (N-(γ-dimethylaminopropyl)-iminodibenzyl hydrochloride, “Tofranil”) has been shown by many investigators to be of value in the treatment of depressive states. The reports of Kuhn (1957, 1958) and of Kielholz and Battegay (1958) have been followed by confirmatory papers from other authors. A number of contributors to the McGill University Symposium on Depression and Allied States (1959) commented favourably on the value of imipramine in depression; Hoff, however, while agreeing that the drug is useful in acute depressions stated that he found it ineffective in chronic depression.

Huntington's Chorea presents us with a good “model” of brain disease in that we know the extent of the contribution of heredity, in contrast to a condition such as schizophrenia regarding which many authors (cf. Alanen, 1958) would be prepared to defend the concept of pseudo-heredity. Secondly the disease carries a fairly uniform prognosis, and finally it results in a distinctive disturbance of motor function which permits of some accuracy in diagnosis and some criterion for objective measurement.

In spite of the publication of Connell's monograph on amphetamine psychoses in 1958, the frequency of such states does not yet seem to be widely recognized even among psychiatrists. Nor is it fully appreciated in what unexpected settings such psychoses can occur, so that many cases must still be overlooked, masquerading for the most part as examples of paranoid schizophrenia.

In this paper the effect of chlorpromazine is compared with that of pecazinet on the schizophrenic population of three chronic psychiatric wards.

Delay, Deniker and Harl (1952) introduced chlorpromazine into psychiatry. Pecazine was first used by Kline and Jacob (1955) and Hiob and Hippius (1955). Thorpe and Baker (1956), in a double-blind, controlled trial, found that both drugs reduced tension significantly in deteriorated, female, schizophrenic patients. Baker and Thorpe (1957) found that pecazine did not significantly reduce daytime incontinence in deteriorated psychotic patients. The trial was controlled and blind. Jones (unpublished), in a double-blind, controlled trial on disturbed psychotic patients, found chlorpromazine to be effective but could find no evidence that pecazine had any effect.

Although the syndrome of internal carotid artery occlusion was first described by Ramsey Hunt in 1915, the neurological complications were not fully appreciated until recent years. Internal carotid occlusion has now been intensively studied, and the criteria for its diagnosis well defined (Webster et al., 1956; Shapiro and Peyton, 1954; McGuire and Jaeger, 1955; Smyth, 1954; Moniz, Lima and de Lacerda, 1937; Hultquist, 1942). Among its clinical manifestations psychiatric features have been mentioned: they range from so-called mental aberrations (Eisenberg, 1955), personality changes, emotional instability and memory loss (McGuire, 1955), to frank dementia (Fisher, 1941). Little attention, however, has been given to the problem of the relationship of bilateral internal carotid occlusion to dementia, and few attempts have been made to document by psychometric testing the degree of intellectual impairment. It is for this reason that a case of bilateral internal carotid occlusion is now reported.

Physical methods play an important part in psychiatric treatment. The roles of electroconvulsive therapy and, to a lesser extent, insulin coma therapy, are fairly well-defined and their effectiveness recognized, though different authorities qualify their recognition in various ways.

The clinical evaluation of a controlled investigation of the effects of Tofranil as an anti-depressant is described elsewhere (Holdway, 1960). This paper describes psychological assessments on the same in-patient sample.

Since the introduction of chlorpromazine with its troublesome side-effects, jaundice, leucopenia, agranulocytosis, photosensivity, etc., the search for safer and more therapeutically effective tranquillizers has continued unabated. Variations of the phenothiazine derivatives based on the promazine ring have been continually introduced with the aim of increased effectiveness together with greater safety.