The action of almost all drugs used so far in psychiatric pharmacotherapy has been directed against psychopathological symptoms or syndromes and not against mental diseases as such, the nosological entities defined by classical clinical psychiatry. In this paper the attention will be drawn towards a different type of drug: compounds with an action specific to a disease rather than to a symptom, and evidence will be presented for the existence within this class of a group that is characterized by being active against affective disorders (manic-depressive psychosis). Normothymotics, “mood-normalizers”, is proposed as a collective name for drugs belonging to this group.

Although the literature is sparse on the subject, the perversions have been successfully treated by behaviour therapy. The treatment is based on the hypothesis that aberrant sexual behaviour has been acquired as a learned response and can be abolished along the lines indicated by learning theory. Raymond (1956) and James (1962) employing aversion techniques, successfully treated cases of glove fetishism and homosexuality respectively. Raymond's patient has since partially relapsed and has been readmitted for further treatment.

The present paper describes a case of fetishism and impotence treated by a combination of aversion therapy and therapy based on reciprocal inhibition (Wolpe, 1958). This case is thought to be of special interest in that to some extent the patient acted as his own control, since previous methods of treatment had been unsuccessful.

Insomnia is widely accepted as a leading feature of that illness designated by the number 301.1 in the International Classification of Diseases. The name given varies—“endogenous depression”, “manic-depressive psychosis/depressive type”, “melancholia” or “depressive illness”. The present generation of laymen (not to say some psychiatrists) use the word “depression” so freely in order to describe an unpleasant, unhappy mood, whether lasting or transient, that one may prefer the term melancholia, or at least “depressive illness”, to signify that condition which justifies the number 301.1. The adjective “endogenous” implies for many that environmental stress plays little or no part in the onset of the illness; we cannot accept that this is always so. The term “reactive” is used in several ways, generally to indicate that the state of unhappiness arises out of some external circumstance and that it would end when circumstances improved or the individual accepted the realities of practical life. The patients used in the present study were suffering from an illness of a kind which we believe may sometimes develop in the absence of severe environmental stress, while in others it may be clearly provoked by circumstances, but the illness, as it develops, may take on a form which becomes largely independent of the environmental circumstances and may continue even when the provoking factors are past; it has become an autonomous melancholia. It will be apparent that by autonomous melancholia we mean an illness shown by clinical experience to respond especially well to electroplexy.

In many electroconvulsive therapy centres atropine is used to mitigate adverse effects resulting from stimulation of the parasympathetic nervous system, while the violence of muscular contractions is controlled with a muscle relaxant. It is customary to secure hypnosis with a short acting barbiturate prior to administration of the relaxant. The first report of the use of thiopentone for E.C.T. was by Rubinstein (1945), and methohexitone (Lilly 25398) was introduced by Friedman (1959). The use of succinylcholine (iodide) for E.C.T. was first reported by Holmberg and Thesleff (1951). The neurological signs during unmodified E.C.T. have been well documented (e.g. Klein and Early, 1948a, 1948b, 1949; Kalinowsky and Hoch, 1952). There is as yet no comparable detailed clinical description of E.C.T. when modified by atropine and a short acting muscle relaxant preceded by a barbiturate. This discussion is limited to some of those signs which may be of assistance in the management of therapy.

Thioproperazine (‘Majeptil’) is a recently introduced phenothiazine derivative which readily produces extra-pyramidal disturbances. Its pharmacology was originally described by Courvoisier et al. (1958) and its clinical properties by a number of workers including, in this country, Denham and Carrick (1961). Several investigators have reported impressive results with this drug in a variety of mentally ill patients, including chronic schizophrenics who had failed to respond to other forms of therapy.

When speech processes are interfered with by the technique known as Delayed Auditory Feedback (D.A.F.) various disturbances result (Lee, 1950, 1951). These have been intensively investigated and have been found to depend upon the delay and amplification of the feedback (Black, 1951) and upon personality factors (Beaumont and Foss, 1957; Spilka, 1954). These differences have been shown to extend into psychiatric diagnoses (Goldfarb and Braunstein, 1958; Spear, 1963) and it has been possible to demonstrate that schizophrenic patients show less increase in vocal intensity under conditions of D.A.F. than do other psychiatric patients and normal subjects. It was thought worth while to investigate this difference further, using a slightly more refined method of measurement of the parameter under consideration and to seek clinical correlations with the findings.

There have been few published reports of the use of E.C.T. in delirious states complicating organic illness. Most psychiatric textbooks with adequate accounts of modern physical treatments allude only briefly to its use in these states, and few medical textbooks mention it at all. Yet the problem of the management of the acutely disturbed delirious patient is not a rarity in medical and surgical wards; in varying degrees delirium may accompany most serious illnesses and prognosis worsens with its persistence. For these reasons it is thought worth placing on record the following cases.

The case records of patients with organic delirium admitted in the past fifteen years to the psychiatric unit of St. George's Hospital were examined. Those cases receiving E.C.T., all seriously disturbed and otherwise unmanageable, are reported in this paper.

Vasomotor rhinorrhoea is a condition characterized by a constant or intermittent watery discharge from the nose. This may be accompanied by bouts of sneezing and a feeling of irritation in the nose. It is stated by some of the patients that symptoms occur during, or are aggravated by, periods of mental tension. In a severe case the secretions may be so profuse that the patient may need to use several handkerchiefs in one day.

Previous studies suggest that chronic schizophrenics differ from normal subjects in their reactions and responses to experimental “sensory deprivation” conditions, not only in that they tolerate these with no difficulty or upset for weeks at a time, but also in that they display what may be an alleviation, albeit temporary, of the degree of severity of some signs of their disorder (Smith and Lewty, 1959; Smith, Thakurdas and Lawes, 1961).

Negative conditioning or aversion therapy is most frequently thought of in relation to the treatment of alcoholism. The article by Franks (1958) gives an excellent review of the general principles involved. However, Eysenck (1960) includes several papers in his book to illustrate the effectiveness of such treatment in cases of homosexuality, writer's cramp (Liversedge and Sylvester, 1955) and fetishism (Raymond, 1956). A suggestion made in the latter was that the fetishist may well become such because of an unusual capacity for quickly forming conditioned responses, and therefore by the same token might equally easily respond to a de-conditioning technique. For this reason, the following case was treated by behaviour therapy by a psychiatrist and clinical psychologist in collaboration, and is reported in support of Raymond's (1956) advocacy of this technique of treatment in similar cases.

Since the introduction of drug therapy in depression, a wide range of pharmacological substances has been made available. It is possible to show that many of these substances are more effective than a placebo in the treatment of depression, but it is not an easy matter to evaluate them in relation to one another.

Since the original observations in Australia by Cade (1949) and Noack and Trautner (1951) on the use of lithium salts in psychiatric practice there has been a modest but steady stream of publications on the subject. The most persistent investigator has been Schou in Denmark (1954, 1955, 1956, 1959), who, with his colleagues, has been able to present a series of manic patients, observed over a sufficient period of time and subjected to controlled conditions, in which the clinical value of the drug has been convincingly demonstrated. Other important series have been reported by Teulié et al. (1955), Rice (1956), Adreani et al. (1958), Kingstone (1960), and Gershon and Yuwiller (1960).

The psychiatric aspects of mitral valvotomy have received relatively little detailed study, and this is all the more surprising since clinicians have commented on the frequency with which mental disturbance appears to follow the operation. This investigation was undertaken in an attempt to establish more precisely than heretofore the extent and nature of the relationship.

The majority of subnormal and severely subnormal patients do not present behaviour problems provided planned daily occupation of mind and body is achieved. In a large mental deficiency hospital, however, there is usually a group of grossly disturbed patients whose behaviour is frequently or continually disturbed, and who fail to respond adequately to drug therapy. These patients present a serious nursing problem since they occupy a disproportionate amount of the nurse's time.

In recent years the development of effective anti-depressant drugs has led to much controversy and uncertainty regarding the treatment of depressive states. Indications for the primary use of E.C.T. remain obscure, whilst choice of drug seems to be determined by current personal preference rather than by any specific rationale. If reliable prognostic formulations—and so, rational lines of treatment—are to be developed, there is an urgent need for the accumulation of data from controlled trials rather than a continuing spate of “1”.

Amitriptyline, a new anti-depressant chemically resembling both imipramine and chlorpromazine has, in a blind controlled study carried out by the authors, been shown to be significantly superior to imipramine in the treatment of female patients between 30 and 70 years of age, hospitalized with primary depressive states (Burt, Gordon, Holt and Hordern, 1962). The findings in the first 74 patients were unexpectedly so much in favour of amitriptyline that to confirm them the trial was extended to include a further 65 patients conforming to the same criteria; but as two died, the total sample consisted of 137 female patients. The size of this sample facilitated (1) an investigation of the phenomenology of depressive states in women and (2) a study of the significance of a number of prognostic variables in relation to the outcome of treatment with amitriptyline and imipramine.

A spontaneous abortion is usually defined as the involuntary expulsion of the foetus before it is of viable age. A woman who has had three consecutive spontaneous abortions is called an habitual spontaneous aborter. The probability that a woman will abort a current pregnancy I call her abortion-probability. In the course of some uncontrolled studies it has been claimed that this probability can be reduced by psychotherapeutic means. For instance, Javert (1957) reported that, using an eclectic treatment, live births resulted from 81.2 per cent. of 154 pregnancies of women who had been habitual aborters. He attributed his success to the psychotherapeutic aspects of his regime.

Ever since E.C.T. was introduced it has been observed that complaints of impaired memory are very common after this form of treatment, but also that the complaints vary considerably in different patients. That memory performances—as they may be measured by means of tests—are disturbed to a varying degree after E.C.T. has been established by several authors. It is thus reasonable to assume that the varying complaints of impaired memory, at least in part, reflect true disturbances of memory abilities. It is a common impression, however, that patients who have gained an obvious release from emotional distress comparatively seldom complain of memory disturbances after E.C.T. Thus, the complaints of memory impairment seem to be determined also by another factor, acting in the opposite direction, viz., improvement of disease. No investigation of the extent to which various factors have influenced the complaints of memory disturbances after E.C.T. seems to have been made.

Benzquinamide (P2647 Pfizer) is a new benzoquinolizine derivative with the structural formula

Animal studies have shown that it is a potent suppressor of conditioned avoidance behaviour, but it does not influence the release of central amines, has little sedative action and is free from serious toxic effect (personal communication, Pfizer Ltd.). An uncontrolled pilot study found it to be effective in relieving anxiety in neurotic patients (Smith, 1962). In the present trial the effect of benzquinamide (P2647) on anxiety symptoms is compared with a placebo and amylobarbitone in the same dosage using the method of sequential analysis.

Amitriptyline, 5-(3 dimethylaminopropylidine)-dibenzo (a,d) (1,4) cycloheptadicne hydrochloride, though chemically and pharmacologically related to imipramine (Barsa and Saunders, 1961) has a tranquillizing effect which is absent with imipramine (Pressman and Weiss, 1961; Bennett, 1961); it acts simultaneously as an antidepressant through its influence on the “anxiety factor” (Freed, 1960; Dorfman, 1960). In contrast to imipramine and the monoamine oxidase inhibitors, amitriptyline has very little influence on the circulatory system and blood pressure (Jensen, 1961) and less proneness to exacerbate the symptoms of schizophrenia (Barsa and Saunders, 1961). Dunlop (1961) noticed a reduction in other symptoms, such as gastrointestinal distress, hyperventilation and vasomotor dysfunction for which amitriptyline was not primarily administered. This he attributed to an anticholinergic side-effect on the central nervous system.

A working party (B.M.J., 1961) recently formulated nine points which they felt distinguished the early childhood psychosis or schizophrenic syndrome of childhood, and this paper describes some features of 100 such patients seen at Great Ormond Street. The nine criteria, which were strictly applied, can be summarized as follows: 1. gross and sustained impairment of emotional relationships with people;