Much work has been done in recent years on the use of individual anti-depressant drugs, but relatively little on comparative studies of their values. So many new drugs have appeared in such rapid succession that the psychiatrist has difficulty in knowing which to choose in the treatment of his depressed patient. The aim of this study was to compare imipramine (Tofranil) and phenelzine (Nardil), both of which had been found by personal experience to be of value in the treatment of depressive states. In the past two years there have been several well-controlled trials of both these drugs which have proved them to be of definite value in the treatment of depression. (Ball and Kiloh, 1959; Harris and Robin, 1960; Holdway, 1960; Hutchinson and Smedberg, 1960; Ashby and Collins, 1961; Rees et al., 1961.) At the time of commencement of this trial imipramine and phenelzine seemed to be the two best antidepressant agents available. It was decided to compare the remission rate or degree of improvement produced by them and the rapidity of response to each. It was hoped to determine what factors in the depressive illness were associated with a good or bad response to either drug. No similar direct comparison of these two drugs had been made, to the writer's knowledge.

A double-blind trial of special design was used to test the efficacy of imipramine hydrochloride (Tofranil) in low dosage in an outpatient setting over a relatively long period. Depressive patients were given Tofranil and placebo at different times during the trial period, and the improvement and side-effects were assessed.

A considerable amount of work has been done on the physiology of sleep (Wolstenholme and O'Connor, 1961; Oswald, 1962) and on psychological functions—reaction time, imagery, etc., in relation to sleep and sleep deprivation (Oswald, 1962). But there have been no systematic investigations of the relationship between sleep and personality differences. The purpose of the present study was to test predictions concerning such relationships generated by general theories and by clinical observation.

When we face the crucial problem of the aetiological basis of the psychoses we have described, there are three main possibilities to be considered. Either they are to be regarded as symptomatic schizophrenias of purely epileptic causation; or they are independent schizophrenias which have appeared in these epileptic subjects coincidentally as the result of pure chance; or they are forms of schizophrenic illness which have arisen in individuals predisposed thereto by the stresses produced by the epilepsy. An investigation of the genetical background is capable of producing evidence which would assist in answering this question. If the first hypothesis is correct, the incidence of schizophrenic psychoses in the relatives of our subjects should be no greater than in the general population. If the second hypothesis is correct, the incidence of schizophrenic psychoses in the relatives should be the same as in the relatives of schizophrenics of the usual kind. If the third hypothesis is correct, we would expect an incidence of schizophrenia in the relatives of our patients which would lie somewhere between these two figures.

Amitriptyline (Tryptizol) is an antidepressant drug which is related structurally to imipramine (Fig. 1). Its full name chemically is 5-(d-dimethylaminopropylidene)-dibenzo (a,d) (1,4) cycloheptadiene hydrochloride. Numerous uncontrolled trials to date (Ayd, Bennett) have reported success with this drug in the treatment of both endogenous and reactive depressions. Several reports (Ayd, Dorfman, Dunlop) have stressed the fact that agitation as a manifestation of depressive illness is frequently relieved. The purpose of this study was to assess the effect of the drug on depression in a controlled trial.

As a specialty within a specialty, child psychiatry has now a well-established place in psychological medicine. Yet differences commonly exist between the practice of child and adult psychiatry which seem greater than can be attributed solely to differences inherent in their respective subject matter. A particular instance is the general emphasis in child psychiatry on individual diagnosis, with little attempt at categorization as compared with adult psychiatry. However, Cameron (1955) has drawn attention to the limitation of the growth of knowledge imposed by a lack of clear description and some classification of the manifestations of disturbance in the child. He considers it essential to focus attention on the manifest clinical picture. Again, Kanner (1957) in his diagnostic formulations, attempts in a few words to describe the main features of the clinical picture as well as the factors considered to be of aetiological importance in the individual case. There remains however, the difficulty of attempting to classify the presenting symptomatology, though some success in identifying patterns of maladjustment has been obtained by statistical methods (Hewitt and Jenkins, 1946; Lorr and Jenkins, 1953; Collins, Maxwell and Cameron, 1962).

Between 14.4.60 and 30.9.60 a follow-up enquiry was carried out, combined with the genetical investigation which has been reported in previous pages. The informants for the genetical enquiry were also the ones who gave information about the patient's recent history. The period covered by follow-up was therefore from one to three years after the time at which hospital investigations had been carried out; and if related to the onset of the schizophrenia-like psychosis was at a mean period of 7.8 years later (range from 2 to 25 years). In addition to this the National Hospital patients have continued to be followed up from that time to the present date, as they and their relatives are asked to attend regularly at a follow-up clinic at the hospital. What is reported here relates to the findings in the special enquiry; but the data that have come in since do not suggest any modification of the conclusions that will be based on the survey of 1960. A synoptic view of these findings is given in Table I.

Anxiety and excitement have been shown by Maas (1961) to increase the rate of breakdown of ascorbic acid, and in schizophrenics this process may be exaggerated by an abnormality of adrenaline metabolism (Briggs, 1962). Schizophrenics receiving “adequate” dietary amounts of vitamin C, as judged by the requirements of the normal population, are commonly found to have low blood ascorbate levels. Evidence of low blood ascorbate levels in most psychiatric patients has been gathered by Horwitt (1942), Leitner and Church (1956) and others. It has been debated whether such laboratory findings are associated with a state of “subscurvy”, where the individual has the complaints of excessive tiredness, depression, irritability and vague ill-health. Many authorities claim that there is no clinical evidence to justify the distinction of a state of “hypovitaminosis C”. They claim that one either absorbs sufficient ascorbic acid to maintain health, or so little that the classical condition of scurvy supervenes.

Claimed by the manufacturers as pharmacologically unique, benzquinamide (P2647) is structurally related to reserpine, and to a lesser degree, chlorpromazine (1). It has been demonstrated as markedly suppressing conditioned avoidance responses in animals without influencing the release of central amines, e.g. norepinephrine and serotonin. Animal studies have suggested that this drug is the least sedating of the benzoquinolizine derivatives, acts rapidly and is non-toxic at the recommended dosage levels.

The task now arises to indicate the significance which should be given to the findings described in earlier pages. There are three possible theories by which the combination of a schizophrenia-like psychosis with a pre-existing epilepsy might be accounted for. First the combination might be co-incidental, due purely to chance, in which case there would be no medical problem of any consequence. Secondly the occurrence of epileptic fits might tend to precipitate the psychosis in individuals genetically predisposed, who otherwise would have had better chances of escaping such a development. Thirdly the psychosis might be the direct consequence of the epilepsy, and therefore to be regarded as an epileptic and not a schizophrenic disorder in the aetiological sense. Fourthly it would be possible to suppose that in any given collection of cases representatives of more than one of these causal chains could be found. These theories may be discussed in turn.