Since the introduction of reserpine by Kline in 1954 there have been relatively few studies of its use in schizophrenia and most of these have been uncontrolled. It is characteristic of these uncontrolled trials that when the results are assessed, they are described in glowing terms, and the percentage of patients reported as showing “moderate” or “marked” improvement is high.

Tranquillizing drugs that have been used in mental deficiency include reserpine, chlorpromazine, promazine, mepazine, hydroxyzine and prochlorperazine.

Esen and Durling (1) thought that the tranquillizing drugs in general were a useful preliminary to psychotherapy. However, the response to individual drugs has been variable.

In the six years since Delay and his associates first used chlorpromazine in psychiatry, at least forty-eight separate side-effects have been attributed to the drug. While many of these are minor, and indeed the majority are readily controlled in in-patients, the search for a phenothiazine of therapeutic value equal to or better than chlorpromazine, but with less or no side-effects, is well worth while. In out-patients there are two reasons for taking side-effects seriously. Firstly, they frequently lead to the patient ceasing to take the drug and thus relapse may occur. Secondly, they may be dangerous or even fatal if unreported—for example the signs of agranulocytosis.

A double-blind controlled trial of iproniazid in endogenous depression and a comparison of its effects with those of E.C.T. was reported in this journal by Kiloh et al. (1960). To summarize the results—of 26 patients treated with iproniazid a good immediate response was found in 14 cases (54 per cent.) whereas only 3 of 28 patients (11 per cent.) given placebo tablets showed a significant improvement at the end of three weeks. Of 27 patients treated with E.C.T. 24 (89 per cent.) showed a good immediate response.

Levomepromazine, levo-3-methoxy-10(2' methyl-3'-dimethylamino-l' propyl) phenothiazine is a phenothiazine derivative which was isolated in the Rhone-Poulenc Laboratories and studied pharmacologically by Sigwald et al. (2) in 1956.

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 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).

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”).

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.

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.

The use of barbiturates in the treatment of insomnia carries a constant risk of habituation and of fatal poisoning from suicidal or accidental overdose. For these reasons, new non-barbiturate hypnotics deserve the closest attention. Ethinamate (“Valmidate”) and methyprylone (“Noludar”) are two such drugs. No trial comparing the hypnotic efficacy of ethinamate with a barbiturate has yet been reported, though Gruber et al. (1954) found the day-time sedative effect of 500 mg. ethinamate to be less (in duration of action) than 100 mg. of quinalbarbitone sodium. Methyprylone has been compared with barbiturate by Stewart (1956) who found 200 mg. equivalent to 100 mg. of amylo- or butobarbitone, by Lasagna (1956) who found 250 mg. equivalent to 100 mg. of pento- or quinal-barbitone, and by Thomson (1958) who found 400 mg. equivalent to 100 mg. of quinalbarbitone.

4-p-Chlorophenyl-1-(3-p-fluorobenzoylpropyl)-4-hydroxypiperidine (R.1625, Haloperidol) is a new compound synthesized by Janssen et al. (1959) and reported to have biological properties similar to those of the phenothiazines at a much lower dosage level. One difference, however, was a greater tendency to potentiate pentobarbitone hypnosis. Von Eiff and Jesdinsky (1960) conducted a “double blind” trial in 28 normal subjects using 4 mg. Haloperidol 2½ or 4½ hours before the experimental period. Subjective effects included fatigue or fatigue and agitation in females. The drug did not appear to influence intellectual function as tested, but reduced self-criticism. There were minor cardio-vascular effects and a tendency to fatigue in ergometry performances. A number of clinical reports have appeared (Divry et al., 1960; Delay et al., 1960) suggesting that Haloperidol is of value in psychomotor agitation and especially in mania in doses of 2–15 mg. daily. Gerle (1960) reports favourably on the drug in schizophrenic patients. Most authors note a high incidence of pseudo-Parkinsonian side-effects (40–80 per cent. of cases) and a section of a recent symposium on the drug in Belgium was devoted to “neurodysleptic syndromes” (dystonic reactions, oculogyric crises, etc.) produced by it. Pichot (1960) at the symposium reported that these reactions can be controlled by chlorpromazine.

There can hardly be a psychiatrist in this country who has not produced parkinsonism in his schizophrenics with reserpine or phenothiazines: Moore, who was among the first in the field in the use of reserpine, spoke of the parkinsonian syndrome, but there was one observation of his that received only passing attention, This was that a small number of his chronic schizophrenics lost their florid schizophrenic symptoms, to be replaced by a clinical picture that he found closely akin to retarded endogenous depression, to the point of contemplated or attempted suicide.

Attention is perhaps insufficiently focused in psychiatry on the “constitutional psychic inferior”. It may therefore be of interest to describe prisoners who have been thus affected at Camp Hill Prison in the Isle of Wight.

The assessment of sex responsiveness is a recurring problem in the field of conduct disorders and psychopathy, particularly when it is desirable to determine the effectiveness of therapy on the behaviour of the sex offender. Previous studies have indicated certain test differences in emotional disturbance and stress reactivity in subjects of known delinquent history, but it has been observed that sex responsiveness may be an additional (separate) factor to consider for the patient who is a known sex offender (19, 20, 21, 22).

Few studies of psychological tests which have been shown to differentiate between psychiatric groups have attempted to follow-up the patients originally tested so as to determine what the predictive power of the test might be in the light of subsequent events. One of these few studies has been reported by Walton (1958) and commented upon by Inglis (1959) who was able to show that the test Walton described was better able to predict the outcome of illness after a follow-up period of two years, than was the original diagnostic label. The importance of this kind of study has been pointed out most clearly by Payne (1958). His argument is that, “Description is only one implication of the diagnostic label. Can the test score aid the doctor in making a prognosis? This need not be the case. Let us consider the original validation of the test again. The doctor who diagnosed the standardization group of patients might well be able to give a more or less accurate prognosis for this group of patients. In fact there might be a significant relationship between the presence or absence of the label he assigns, and prognosis. We also know that there is a significant correlation between presence or absence of his label and the test scores. This does not prove, however, that there is any relationship whatsoever between the diagnostic test score and prognosis. Two things which correlate with the same thing do not necessarily correlate with each other, unless the correlations concerned are greater than ·7” (1958, p. 27).

The purpose of the investigation was the assessment of dementia from a clinical and EEG viewpoint in patients aged 60 and over, resident in a mental hospital containing a high proportion of elderly long-stay persons. All patients of suitable age were examined irrespective of diagnosis, provided that this was technically possible and, if alive, they were re-examined three years later, in the hope that a longitudinal study would give additional information as suggested by Roseman et al. (1952) and Sheridan et al. (1955).

The increasing use of tranquillizers in the treatment of mental disorders has made it imperative to study both the immediate and long-term effects of these drugs in order to establish their limits of safety. One of the approaches that appeared important to us was the correlation of the histological findings (Roizin, True and Knight, 1959) with tissue levels of the drug. In addition to its significance from the pathological standpoint, such a study may also furnish information towards a better understanding of the mechanism of action of these drugs.

Convulsive therapy as a form of treatment for schizophrenia originated very soon after insulin coma treatment and the induction of convulsions by an electric current was first used by Cerletti and Bini in 1938. For many years insulin comas were regarded as the treatment of choice, although E.C.T. was recognized as having some value, particularly in catatonic conditions. In the last eight years the advent of effective chemical therapy with the tranquillizers has tended to overshadow the value of any other form of treatment.

In view of their many inter-connections with the cortical grey matter, the effects of lesions in the basal cerebral nuclei are of the greatest theoretical interest. On account of the rarity of naturally occurring lesions confined to these nuclei, there have been few reports of psychological changes in patients with discrete subcortical lesions. Smyth and Stern (1938) described four cases of intrinsic tumour of the thalamus, all of whom gave evidence of organic dementia early in the course of the disease. Eaton et al. (1939) reported six cases of symmetrical cerebral calcification preponderating in the basal ganglia, with no radiographic evidence of cerebral atrophy, of which the clinical concomitants included mental retardation. Alford (1948) has gone so far as to insist that destruction of thalamic nuclei is alone responsible for intellectual impairment, and that “focal” defects associated with different cortical lesions are related either to sensory disturbances or to the psychiatric state of the patient.