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Because of an error in the manufacture of digoxin tablets a large number of patients took tablets that contained 0·20 mg. of digitoxin and 0·05 mg. of digoxin instead of the prescribed 0·25 mg. of digoxin. The symptoms are described of 179 patients who took these tablets and suffered from digitalis intoxication. Of these patients, 125 had taken the faultily composed tablets for more than three weeks. In 48 patients 105 separate disturbances in rhythm or in atrioventricular conduction were observed on the electrocardiogram. Extreme fatigue and serious eye conditions were observed in 95% of the patients. Twelve patients had a transient psychosis. Extensive ophthalmological observations indicated that the visual complaints were most probably caused by a transient retrobulbar neuritis.

Forty-eight patients with anxiety states were treated with oxazepam (Serenid-D), which was administered in tablets of three different colours—red, yellow, and green. Every patient received one week9s treatment with each colour, according to a random programme. A latin square design was used to ensure complete balance between the colours and between the weeks. The patients9 symptoms were categorized and then assessed by both weekly physicians9 ratings and daily self-rating, which showed close agreement. Colour preference was shown on both these scales in that symptoms of anxiety were most improved with green, whereas depressive symptoms appeared to respond best to yellow. Such colour preferences, however, did not reach levels of statistical significance, except for phobias as rated on the physicians9 assessment. The results indicate that colour may play a part in the response to a drug.

Significant variations in the incidence of depression and loss of libido were found with the various types of oral contraceptives. The highest incidence occurred with strongly progestogenic compounds (especially with those containing a small amount of oestrogen) which have high monoamine oxidase activity for most of the cycle. The lowest incidence was found with the strongly oestrogenic sequential regimens which have weak monoamine oxidase activity for most of the cycle.

A self-administered questionary (the General Health Questionnaire) aimed at detecting current psychiatric disturbance was given to 553 consecutive attenders to a general practitioner9s surgery. A sample of 200 of these patients was given an independent assessment of their mental state by a psychiatrist using a standardized psychiatric interview. Over 90% of the patients were correctly classified as “well” or “ill” by the questionary, and the correlation between questionary score and the clinical assessment of severity of disturbance was found to be +0·80. The “conspicuous psychiatric morbidity” of a suburban general practice assessed by a general practitioner who was himself a psychiatrist and validated against independent psychiatric assessment was found to be 20%. “Hidden psychiatric morbidity” was found to account for one-third of all disturbed patients. These patients were similar to patients with “conspicuous illnesses” in terms both of degree of disturbance and the course of their illnesses at six-month follow-up, but were distinguished by their attitude to their illness and by usually presenting a physical symptom to the general practitioner. When 87 patients who had been assessed as psychiatric cases at the index consultation were called back for follow-up six months later, two-thirds of them were functioning in the normal range. Frequency of attendance at the surgery in the six months following index consultation was found to have only a modest relationship to severity of psychiatric disturbance. It is argued that minor affective illnesses and physical complaints often accompany each other and usually have a good prognosis.

Of 261 women who completed a self-rating scale for measuring depression, 168 were taking oral contraceptives and 93 were using physical methods of contraception. Of the group of women taking oral contraceptives 6.6% were more severely depressed than any of the control group. There was a significant variation in the depth of depression related to the day of the menstrual cycle in the control group. This association was not found in the oral contraceptive group, where premenstrual depression was limited to the one or two days preceding menstruation.Women taking a contraceptive containing lynoestrenol 2.5 mg. and mestranol 0.075 mg. showed a significantly increased incidence of pessimism, feelings of dissatisfaction, crying, and tension, compared with women taking other oral contraceptives and the control group.

Measures of subjective feeling used by five patients indicated that depression of mood occurred about four days after fenfluramine withdrawal. An experiment in which another 11 patients took fenfluramine 80 mg for 28 days confirmed the depression, maximal on the fourth withdrawal day. It also indicated that in the first week of administration there was some mood elevation, but with feelings of impaired ability to concentrate. The drug reduced appetite and weight. A comparison is drawn with imipramine, which was found to induce initial and withdrawal changes of subjective experience (of dreaming) in six volunteers. It is suggested that certain mood-influencing drugs may not be drugs of abuse because of some unpleasant initial effects, though they can be drugs of dependence.

The psychiatric inpatient population from Salford was analysed in five successive annual censuses, from 1 January 1968 to 1 January 1972. Short-stay and medium-stay patients (under one year) remained constant. Long-stay patients reduced only slowly, and the length of stay increased. Over 200 patients (60%) had been in for 20 years or more at 1 January 1972. Analysis showed that the 1968 long-stay cohort diminished by 122 patients (29%) in four years, while 54 new long-stay patients accumulated. There seems little prospect of emptying large psychiatric hospitals of their long-stay population.

Of 106 patients admitted for investigation to a neurological hospital with a presumptive diagnosis of dementia, 84 were confirmed to have intellectual impairment or loss of learning and memory function or both. A possible aetiology for the dementia was found in 36 of these 84 patients; the commonest causes discovered were intracranial mass lesions, arterial disease, and alcoholism. Fifteen of the 106 patients were found not to be demented but to have some other illness, most commonly depression. Of the whole series some 15% of the patients suffered from conditions that were amenable to treatment.

It is surprising that, so far as we can ascertain, no trial has been reported in which the efficacy of a modern "anti depressive " drug has been compared with that of a combina tion of drugs (dexamphetamine and amylobarbitone) widely used in the treatment of depressive illness before the newer drugs were introduced five or six years ago. Proprietary mixtures of dexamphetamine and amylobarbitone are still advertised as of value in depression, and the lack of any comparative trial is perhaps more surprising when it is remembered that the basic cost to the National Health Service of a week's treatment with the ingredients of such mixtures (dexamphetamine sulphate 5 mg. and amylobarbitone sodium 50 mg. t.i.d.) is 5d., while that of the currently most popular antidepressant (imipramine hydrochloride (" tofranil ") 50 mg. t.i.d.) is about 11s. 6d. In this paper we report a controlled comparative trial of imipramine and a proprietary mixture of dexamphetamine and amylobarbitone ("drinamyl"), in the treatment of depressive illness.

The increasing number of children admitted to this hospital with poisoning by tricyclic antidepressants is causing concern. Of 60 children admitted between January 1966 and July 1973, half were admitted in the last 18 months. In 60% of these patients the tricyclic compounds had been prescribed for nocturnal enuresis. One child aged 2 years and 4 months died of imipramine poisoning. It is imperative that all children with poisoning by tricyclic compounds, irrespective of the dosage, are admitted to hospital for continuous cardiac monitoring. Cardiac arrhythmias induced in children by amitriptyline and imipramine are prominent and dangerous.In the earlier years of this survey the antidepressants taken by children had usually been prescribed for adults, but recently they have been increasingly prescribed as a treatment for enuresis in children themselves. Medicine for a trivial complaint is unlikely to be regarded by parents as potentially dangerous and practitioners should therefore warn them accordingly; if, indeed, the transient effect of these potentially dangerous drugs upon the average case of bed-wetting in childhood can be justified.

Fifty patients with severe depression were separated into two groups by the responses of their plasma 11-hydroxycorticosteriod levels to a midnight dose of 2 mg. of dexamethasone. Clinical and questionary comparisons were made between the two groups of patients, who were similar as regards age, sex, and length of symptoms before admission to hospital. No differences were found between the groups of severely ill patients as regards the severity of their depression and anxiety assessed by questionary. Nevertheless, agitation was significantly greater in the patients whose corticosteroid levels were not suppressed by dexamethasone and adverse childhood experiences in those whose levels were suppressed.

Use of the midnight dexamethasone suppression test showed that the plasma 11-hydroxycorticosteroid (11-O.H.C.S.) level did not undergo its normal reduction in 14 out of 27 patients with severe depression. Resistance to dexamethasone suppression correlated with the clinical rating of the severity of depression, while recovery from depression was associated with return of normal responsiveness to dexamethasone. The explanation of these findings is unknown.

An inverse relation has been suggested between the incidence of depressive illness and the opportunity to externalize aggressive behaviour. The riot situation in Belfast in 1969-70 provided an opportunity to study this hypothesis. The incidences of depressive illness in the city and a neighbouring peaceful rural county were compared over a number of years. Data regarding age, sex, area of the city, and type of depression were obtained. The city was divided into areas and four of these were studied in detail. Similar data were obtained for persons showing aggressive behaviour. There was a significant decrease in depressive illness in Belfast in both sexes and all age groups. This was more pronounced in males but the decrease was confined to those in social groups IV and V. The decrease was more significant in riot areas. The suicide rate fell by almost 50% and there was a noticeable increase in the rates of homicide and crimes of violence. In contrast the rural county showed a sharp increase in male depressives.

Two elderly patients suffering from manic-depressive psychosis/depressive reaction had concurrently hypercalcaemia from vitamin D intoxication. They developed hypernatraemia with severe potassium and water depletion. Hypercalcaemia was pronounced, but both patients recovered quickly and their depressive symptoms resolved following water and potassium repletion and corticosteroid therapy.

Respiratory pattern and arterial blood gas tensions were assessed in patients with acute cerebrovascular accidents. Hyperventilation, low Pco(2), and high arterial pH were associated with a poor prognosis, whereas patients with normal respiratory pattern and blood gas tensions survived. Periodic and Cheyne-Stokes breathing carried an intermediate prognosis.

Electric convulsion therapy (E.C.T.) was used in the treatment of 13 women inpatients suffering from depressive symptoms. Twelve of the patients showed a significant increase in urinary excretion of 3′, 5′ cyclic adenosine monophosphate (cAMP) on the day of treatment, whereas four controls who received all or part of the preliminary treatment but no electric shock showed a reduction. The results of this study are consistent with the hypothesis that the antidepressant action of E.C.T. is mediated through an increased production of cAMP in brain tissue.

A few patients may be of normal intelligence but have difficulties in reading, writing, and spelling, which are the main precipitants of a psychiatric disorder. In seven patients this illiteracy emerged only after intensive examination, as they had hidden it from employers, friends, and children. Characteristically these patients are often very sensitive about this disability and marital friction is common. They are also often noticeably resistant to remedial help.

The limited value of plasma measurements in the management of treatment with lithium is discussed in the light of the mechanisms of its therapeutic actions and toxic effects.The plasma level of lithium usually rises twofold or threefold in the three to five hours after ingestion of each dose of delayed-release tablets and then gradually falls. The precise shape and height of the lithium curve depend on gastric emptying, which can be slowed with propantheline or speeded with metoclopramide. Depressed or demented patients may be irregular in taking their tablets and variable in food intake. Both the time of the blood test and this behaviour must be considered before changing the prescribed dose of lithium salt because of a laboratory result. A lithium tolerance curve may be a safer guide to treatment than single measures.Mild intermittent thirst is a common early side effect, and severe persistent thirst with polyuria is an uncommon later effect of daily intakes of at least 1,500 mg lithium carbonate. This diabetes insipidus is reversible, non-progressive, unrelated to plasma level, and distinct in attack from lithium-induced hypothyroidism, which may occur at low dosage but is also usually of late onset and reversible or treatable with thyroxine while lithium is continued. Obesity is another occasional effect of large doses. These side effects and the antimanic and prophylactic effects may have different mechanisms.

During a study of 72 patients submitted to jejeunoileostomy for obesity seven were found in whom compulsive, episodic overeating was associated with depressive mood disturbance. When followed up nine to 27 months after operation all seven had lost weight and had also lost the habit of compulsive eating. In all cases psychiatric symptoms improved or disappeared, and symptom substitution was not observed. Obesity rather than psychiatric disorder is usually the main problem in such patients. The implications for psychoanalytic and other concepts of obesity are discussed.

Measurements of subjective feeling in 20 patients receiving fenfluramine alternating with placebo and in 19 patients receiving phentermine alternating with placebo indicated that depression of mood occurred four days after fenfluramine withdrawal but no such depression was seen with phentermine.

A 21-tablet oral contraceptive packet containing .5 mg dl-norgestrel and .03 mg estradiol was clinically tested in 1085 women of reproductive age for a total of 7323 cycles. There was 1 pregnancy which may have been due to incorrect tablet use. 98.2% of the cycles fell within a 28-day plus or minus 3-day pattern. 21% of the women had some breakthrough bleeding at some time, but it was confined to 1 cycle in 63% and not more than 2 cycles in 82%. The contraceptive is recommended for general use on the bases of how pregnancy rate, mean intermenstrual bleeding of .54 days per cycle, and the mean total bleeding of 4.87 days per cycle. The hypothesis that an effective combined oral contraceptive using norgestrel as the progestogen can employ as little as 30 mcg of estrogen is supported.

Four patients with active Paget's disease were treated with the RNA inhibitor actinomycin D. Three were clinically improved after treatment; the fourth had multiple collapsed vertebrae and showed no symptomatic improvement. Striking changes took place in urinary calcium and hydroxyproline, in serum alkaline phosphatase, and to a less extent in serum calcium and phosphate. These studies are continuing and are being compared with the effects of mithramycin.

A ten-year follow-up of 886 shoplifters showed clear differences between women and men. Men tended to have previous convictions and to steal books (unknown in women). Of the 532 women nearly one third were foreign-born, and this group comprised 46% of offenders aged 17-30. The peak age among British women was 51-60. First offenders accounted for 80% of the women, and their reconviction rate was 11%; among those with any kind of previous conviction the rate was 50%. The rate of admission to hospital for women shoplifters is three times higher than average.

Seventy-two patients with eczema were randomly allotted to one of two treatment groups: A, those receiving dermatological treatment only, and B, those receiving the same dermatological treatment plus psychiatric treatment, limited where possible to four months. Cases were followed up at six-monthly dermatological assessments, 57 (79%) for 18 months. The findings suggest that in the presence of overt emotional disturbance, of new psychological or psychophysiological symptoms preceding the rash by up to a year, and of high motivation for it, brief psychiatric treatment improves the outcome in eczema (the proportion clear at 18 months was about doubled), whereas in their absence such treatment may worsen it, especially in the short term.

Depressed fractures, or congenital moulding depressions, of the skull in the newborn are uncommon. It is accepted that these depressions are of two types : the majority are caused by forceps or digital pressure from the obstetrician's hand, while a small number are due to extreme moulding of the foetal skull to permit its passage through the mother's pelvis. The latter appear to be extremely rare, since a search of the literature reveals only 18 cases?five in America (Ingraham and Matson, 1954 ; Rawl, 1957 ; Pike, 1958) and 13 in French journals (Paillas et al., 1955 ; Thurel and Baldacci, 1957)?although passing reference is made to them in textbooks of paediatrics and neurosurgery. In the past three years 31 cases have been seen in the Neuro surgical Unit of the Harare Central Hospital, Salisbury,A Rhodesia. . All these cases occurred in African women, delivered at the Harare Hospital Maternity Centre, at hospitals served by Harare Hospital, or unattended at their homes. In only three cases was there any obstetrical intervention, and in each one it seems doubtful that the intervention caused the depression. We estimated an approximate and somewhat high incidence of one in 4,000 births, while during the same period (three years) one instrumentally produced depression was observed in deliveries of 6,000 European women at the Lady Chancellor Maternity Hospital. In this country, therefore, spontaneous moulding depressions appear to be relatively common among African women. It is because of this, and its rarity in Europeans, and also the paucity of discussions in the literature, that our atten tion has been focused on this condition, both as a medical curiosity and from the aspects of prevention and cure. The condition commonly consists of a depression varying in size from a small groove to an indentation of the entire half of the frontal bone, running from the supraorbital ridge up to but never passing beyond the coronal suture (Figs.' 1 and 2), although other bones may be involved. Tracz (1960) points out that in most cases these are not true fractures but indentations of malleable bone without loss of continuity, and he postulates that they may be caused by pressure of the foetal skull from any of the following: the symphysis pubis, the sacral promontory, a deformed pelvis, obstetrical forceps, or the obstetrician's hand during manual rotation.

Electric aversion was administered to 14 cigarette smokers. Six of the nine who completed the treatment were still abstinent at one-year follow-up. Three cases relapsed (at one, three, and four months) and five dropped out of treatment. Depression was a troublesome side-effect and was responsible for two of the drop-outs. The overall average of 21·5 cigarettes on the day before treatment dropped to an average of 1·4 cigarettes per day after the third aversion session, and though individual response varied widely most patients stopped smoking within five sessions. It is concluded that electric aversion is a powerful suppressor of cigarette smoking, but more experience is needed to ensure its best use as a measure to achieve permanent abstinence. Its use is limited to a small group of well-motivated smokers.

The relationship between plasma concentration of nortriptyline and therapeutic effect after two weeks' treatment with the drug was investigated in 29 psychiatric inpatients. Endogenous depression was diagnosed in all patients. Amelioration of depressive symptoms was estimated as reduction in score on a rating scale, based on a psychiatric interview. Amelioration was not correlated to the patient's sex or age. There was a curved relationship between plasma level of nortriptyline and therapeutic effect. Amelioration was most pronounced in the intermediate plasma level range (50-139 ng nortriptyline/ml plasma) and was slight both at lower and at higher plasma levels. This type of relationship may be due to the dual action of tricyclic antidepressants which has been found in animal experiments. On larger dosages a phenothiazine-like blockade of the monoaminergic receptor is added to the blockade of monoamine reuptake thought to be related to the antidepressant action of the drugs.THIS STUDY THUS SUGGESTS TWO POSSIBLE REASONS FOR A THERAPEUTIC FAILURE WITH NORTRIPTYLINE: a too low or a too high plasma level. The large individual variation in the pharmacokinetics of the tricyclic antidepressants makes prediction of plasma level from dosage in a given individual virtually impossible without knowledge of rate of elimination and apparent volume of distribution. Hence monitoring plasma levels may be a way to increase the efficacy of treatment with these drugs.

Depression, headaches, and libido were rated in 272 women before starting a contraceptive method and at intervals during the first year of use—54 were fitted with an intrauterine device (I.U.D.) and 218 used one of three oral contraceptives. Side effects caused 25% of the oral contraceptive group and 13% of the I.U.D. group to stop the method. Depression, headaches, and loss of libido were the most common reasons for stopping oral contraceptives and breakthrough bleeding was the most common reason for stopping the I.U.D. The group of women who stopped or changed their oral contraceptives during the survey were compared with the group who remained on the same oral contraceptive throughout. The former had higher mean depression and neuroticism scores at the first clinic visit and contained more women with a history of premenstrual weepiness, depression during pregnancy, outpatient psychiatric treatment, and treatment with antidepressants. Changes in the depression, headache, and libido ratings throughout the survey are presented.

Sixteen patients in whom schizophrenia was initially diagnosed and who were treated with fluphenazine enanthate or decanoate developed severe depression for a short period after the injection. In five cases this depression is thought to have been responsible for suicide. In 8 out of 10 cases the depression responded to electroplexy (E.C.T.). It is recommended that patients who are treated with fluphenazine should be carefully supervised.

The clinical presentation of three patients with meningiomas at different frontal sites is described. They had been ill for 3, 25, and 43 years before the tumour was demonstrated radiologically. Apathy, incontinence, dementia, and fits were seen in association with middle and superior frontal lesions, and may be mistaken for symptoms of involutional depression or presenile cerebral atrophy. In contrast, excitement and hallucinosis were seen in association with a basal frontal lesion, and may mimic psychotic syndromes like hypomania and schizophrenia, particularly if the tumour encroaches on the third ventricle and adjacent structures. Irreversible loss of myelin and axons in the frontal areas of brain surrounding the tumour may have contributed to the clinical picture of the syndrome shown by these patients.

A controlled double-blind trial of amitriptyline at two dosage levels (75 and 150 mg/day), amylobarbitone (150 mg/day), and an inert substance for a period of four weeks was conducted on four matched groups of women attending their general practitioners and suffering from a depressive illness. Improvement at 7 and 28 days was noted on several measures of depression and anxiety in all treatment groups. Of these treatments amitriptyline 150 mg/day was the most consistent in relieving depression and anxiety. Troublesome side effects were equally distributed among the four treatments.

With the co-operation of the family doctors in five selected urban general practices the general-practitioner treatment of 73 patients suffering from a new episode of depressive illness was evaluated over a period of four months. The purpose was to test the belief that general practitioners are best fitted to manage most psychological ailments, and depression was chosen as the psychiatric illness most commonly seen in general practice. Medication was the principal treatment offered, and this was often inadequate in dosage or the patient defaulted. Drug defaulting was thought to be due partly to failure of supervision and follow-up and to too low a consultation rate. The low consultation rate was also thought to explain why few patients thought there was a therapeutic value in the doctor-patient relationship. The results of the study indicate that patients with depressive illness do not receive the best treatment in general practice. The reasons are several and responsibility must be shared by the medical practitioners, the current system of the general practice, and the patients themselves.

Two hundred patients treated by ileorectal anastomosis for ulcerative colitis were questioned about their opinion of the result of their operation. The vast majority of patients led normal business and social lives and their activities had been greatly altered for the better by this operation.