This paper describes a comparison of two therapeutic regimes for depressive illness: (a) imipramine, and (b) a preparation containing amitriptyline hydrochloride and perphenazine in the ratio 25:2 (Triptafen-DA).

As part of a larger study of cognitive disorder among the schizophrenias (Foulds et al., 1967a, 1967b), aspects of retardation were investigated. The relation of retardation to other forms of thought disorder in schizophrenia has been extensively investigated by Payne (Payne, 1960, 1962; Payne, Ancevich and Laverty, 1963; Payne, Caird and Laverty, 1964; Payne and Caird, 1967) who has used the three Babcock tests (Babcock and Levy, 1940), and the Wechsler Digit Symbol test as his measuring instruments.

Referrals for psychiatric specialist treatment under the National Health Service have increased steadily in numbers, until the annual rate for new patients in England and Wales now stands at over 200,000 (Ministry of Health, 1965). The trend has led some critical observers to conclude that, in the words of one of their number, “Partly because it has oversold itself psychiatry has become oversubscribed” (Kessel, 1963). This is a serious charge, but in the absence of proper evaluative studies it must be judged non proven.

In a previous investigation, the concentration of homovanillic acid (HVA) seemed to be related to the degree of dementia (Gottfries et al., 1965). The object of the present work is the further study of the occurrence of HVA in the human brain, especially with regard to senile dementia. The hypothesis is that senile dementia is a disease with a disturbance in the monoamine metabolism, which is reflected in a reduction of HVA in the neostriatum.

Emotional disturbance during pregnancy and the postpartum period is very common and at times leads to serious psychotic reactions. Studies comparing the relative frequency of psychotic breakdown in women during pregnancy or postpartum, or at other times, indicate that there is a greater frequency of psychotic reaction in the postpartum period (Pugh et al., 1963; Ryle, 1961; Tobin, 1957; Strecker and Ebaugh, 1926; Richardson and Guttmacher, 1967).

All hitherto applied antidepressant drugs, both the tricyclic compounds and the MAO inhibitors, present serious disadvantages, not only some more or less grave undesirable side-effects, but also a rather long latency time before the antidepressant effect itself strikes through.

The prognosis for patients with senile dementia after admission to hospital has generally been regarded as poor, it being thought that by the time the illness reached a stage necessitating admission life expectation was very low. Figures obtained by Roth (1955) support this view; only 18 per cent of his patients with senile dementia survived for more than two years. The prognosis for atherosclerotic dementia was rather better, with approximately 27 per cent still alive at the end of two years.

Some investigations suggest that the attitude of a psychiatrist to therapy with drugs may affect his patient's response to treatment (Sheard, 1963; Reynolds, Joyce, Swift, Tooley and Weatherall, 1965), though the evidence is far from conclusive and earlier findings have not always been confirmed by further research (Hordern and Hamilton, 1963; Uhlenhuth and Park, 1964). The possibility that a particular drug may be more effective if administered by a physician who believes it to be superior to alternative drugs appears to have received little attention. Such preferences exist in medical practice. The present study was undertaken to test the hypothesis that they have a measurable effect, provided the drug is administered knowingly. The efficacy of the drug of choice of three psychiatrists was therefore compared (a) under single blind and double blind conditions, and (b) with that of alternative medication.

In a previous paper (Hodges, Jones, Elithorn and Bridges, 1964) we reported on adrenocortical activity in depressed and schizophrenic patients as revealed by plasma cortisol levels before and after electro-convulsive therapy (E.C.T.). Close similarity was found between the two groups except for three depressed patients who appeared to show considerably higher cortisol levels after the treatment than did the remaining subjects. The patients were examined at random different treatments during the whole treatment course and it appeared possible, both that the observed cortisol response to E.C.T. might depend partly on which treatment of the series in a whole course was under examination, and also that the response of the illness to therapy might be a significant factor. It was therefore decided to observe in a number of subjects the response to successive treatments throughout courses of E.C.T.

The natural history of alcoholism has been described by Trice and Wahl (1958) and by Glatt (1967). The “average” alcoholic first begins drinking when aged 18, and by the time he is 26 he is drinking heavily and frequently becomes drunk. He begins to experience blackouts between the ages of 30 and 35, and a number of years later he is no longer able to control his intake of alcohol. He begins to lose contact with his family and friends and starts drinking alone. By the middle of the fifth decade he has reached his lowest point and seeks admission to hospital. In a proportion of cases∗ this process is markedly accelerated and patients aged 30 or less are admitted to hospital because of alcohol dependence.

During the past two decades an increasing number of investigations have been made into the relationship between maternal age and incidence of disease. The following may be mentioned by way of illustration.

Psychiatric patients frequently make somatic complaints which are not related to physical pathology, but this is often not fully appreciated by medical practitioners other than psychiatrists. Dowling and Knox (1964) have shown that depressive patients are often diagnosed as physically ill, especially if they have had a notable physical illness in the previous five years. Stoeckle and Davidson (1962) note that depressive patients are frequently referred to medical and surgical clinics and sometimes receive inappropriate treatment as a result. Sainsbury (1960) showed that gynaecological patients are, on average, more neurotic than normal. The present author (Munro, 1964) found that depressive women were excessively liable to have undergone a gynaecological operation in the year preceding their admission to psychiatric hospital.

In 1951, J. Cammermeyer and R. Gjessing (I) reported one case of fatal myocardial fat embolism in periodic catatonia with fatty liver. This patient had suffered from periodic catatonia for many years and had been investigated by R. Gjessing (28) for a considerable number of years. One day in the beginning of a psychotic phase he suddenly died. His death was explained by the histological demonstration of fat emboli in the myocardium. A careful clinical survey of the patient and study of his case record failed to reveal any of the usual sources of fat embolism, but a centrolobular fatty degeneration of severe degree was found in the liver which was assumed to be the source of fat emboli.

In an earlier investigation, Hassall and Foulds (1968) demonstrated certain differences between a group of alcoholics of 30 years and under and a matched control group. Such a group is not, of course, representative even of those alcoholics who come to psychiatric treatment. The present investigation was concerned to assess a wider range of such alcoholics, and try to determine whether any differences which might be found within this group could be attributed to chronological age, to age of onset of excessive drinking, or to length of time during which excessive drinking had been taking place.

The purpose of this study was to evaluate the extent of depressive side effects in women of child-bearing age currently taking oral contraceptives. The incidence of depression has been variously reported as between 2 per cent. and 5 per cent. (Any Questions, 1965), but clinical impression has been that this is an underestimate. Rather alarmingly, also, there has been a tendency to explain away symptomatology on a “scapegoat effect” basis (Bakker and Dightman, 1966). By blaming the Pill the patient has been held to increase her own self-esteem and avoid responsibility for lethargy, irritability, etc. Nevertheless, alert physicians have consistently recommended caution (Kaye, 1963; Grant, 1965).

Klinefelter, Reifenstein and Albright (13) in 1942 collected and described nine cases of a new clinical syndrome, later given the eponym Klinefelter's Syndrome, which appeared at puberty in males and was characterized by gynaecomastia, hypogonadism, aspermatogenesis, increased follicle-stimulating hormone (F.S.H.) and normal or low 17-ketosteroid urinary excretion.

Most of the studies of steroid metabolism in depression conducted thus far have been of glucocorticoid activity. Rubin and Mandell (31) reviewed adrenal cortisol production in pathological emotional states and concluded that there was ample evidence of heightened cortical release of 17-hydroxycorticoids (17 OHGS) in depression.

The tricyclic antidepressant drugs are established therapeutic agents, yet their mode of action has remained obscure. The usual delay of some 10 or more days before they produce beneficial effects has never been satisfactorily explained. Many months are usually necessary for lasting cure, for often symptoms recur when the drugs are stopped. If they are then reinstated for several months, and then stopped, the patient commonly remains free of symptoms. There is thus uncertainty as to whether the drugs might simply be masking the depression in a manner comparable to anxiety-relieving agents, and uncertainty whether patients should be regarded as temporarily dependent upon tricyclic drugs. Slow brain processes have to be inferred, of a duration often met in psychiatry (Oswald, 1967). The observations we now report have features in common with many other slow brain recovery processes Oswald, 1969) and may cast light upon the mode of action of antidepressant drugs, as well as providing further insight into the chemical mechanisms of sleep. The latter are currently believed to be governed in part by cerebral mono-amines, which the tricyclic drugs are thought to affect.

Concern has been expressed in many quarters about the size of the problem of alcoholism in Great Britain, although there are no figures available from a direct count in the general population. Morrison (1964) has adduced evidence that the size of the problem doubled between 1956 and 1961 and that alcoholism is perhaps four or five times more prevalent in Scotland than in England and Wales. Existing treatment facilities have been criticized and the establishment of special units for the treatment of alcoholics has been advocated (Ministry of Health, 1962). One such unit was opened in Edinburgh in 1963 (Walton et al., 1966), and the opening of further units in Scotland is being considered (Scottish Home and Health Department, 1965).

In a previous paper (Abe and Moran, 1969) we analysed observed increases in paternal and maternal ages in 291 male homosexuals admitted to the out-patient or in-patient departments of the Bethlem Royal and Maudsley Hospitals during 1949–1960. It was shown that the mean mothers’ age of these patients was 2.31 years greater than would be expected in the general population after taking account of the years of birth of the patients. The similar shift in mean paternal age, using an indirect method of calculating the expectation, was between 3.15 and 3.55 years. On carrying out an approximate regression analysis of each of these shifts on the other it was shown that the shift in maternal age could be completely explained as an effect due to a shift in paternal age, but not vice versa.