Fifty-four acutely manic patients were allocated to treatment on a double-blind basis with either carbamazepine or lithium carbonate. The short-term effects of treatment were studied over a period of six weeks and the longer term, prophylactic, effects over a period of up to a year. Additional ‘rescue’ medication was allowed when clinically indicated. There was a high drop-out rate from the trial. Despite this, it appeared that valid comparisons between the two treatments could be made. No statistically significant differences were found, but carbamazepine appeared slightly less effective as a treatment for acute mania and more effective as a prophylactic treatment in this group of patients. Possible predictors of individual responsiveness to each treatment are discussed.

There has been a growing number of reports of psychiatrists moving out into primary-care settings. We report a survey of consultant psychiatrists to assess the extent of this practice in Scotland. Some time spent in the primary-care setting was reported by 56%, the figures being highest in rural areas. An equal number of non-consultant medical staff were involved. Most schemes were initiated by psychiatrists, over half of whom had had some postgraduate general-practice experience. A similar survey in England and Wales showed that only 19% of consultant psychiatrists spent time in primary-care settings, a smaller proportion of non-consultant staff being involved. The value of working in primary-care settings has yet to be assessed.

The skin is by far the largest organ of the body and it performs a variety of important functions. In both a concrete and symbolic sense the skin serves as a boundary separating the inner person from the outer world, self from non-self. It is evident therefore that cutaneous awareness is a central part of overall body image. It should be no surprise to learn how frequently real, imaginary or factitious dermal-pathology may occur in association with psychiatric disorder. The false idea that something is alive and moving in the skin has been presented to dermatologists and, to a lesser extent, psychiatrists for many years. It has attracted a ready psychodynamic explanation based on the concept of somatisation of emotional experience, and taking into account the symbolic function of the target organ.

The efficacy of antidepressants is measured primarily by their ability to treat the acute symptoms of depression yet the underlying process may take longer to resolve. A period of emotional frailty follows resolution of the acute stage, during which the patient, although apparently symptom-free, is prone to suffer relapse of the original symptoms. Antidepressants should not be stopped immediately a response is observed, but should be given for a longer period to prevent early relapse. In those suffering from recurrent depression, long-term treatment may prevent later recurrences of new episodes of depression.

The distinction between relapse of old symptoms and recurrence of new episodes is of particular importance, both in assessing efficacy of antidepressants during the continuation phase of acute treatment and in the separate assessment of their prophylactic efficacy. Unfortunately, though, many investigations have failed to distinguish between these two distinct phenomena. Klerman & Paykel (1970) emphasised the need to distinguish between early return of depressive symptoms, which they label ‘relapses’, from the later new episodes which they term ‘recurrence’. However, there has been a general lack of systematic investigation of this question, as well as a failure to use sufficiently precise methodology to distinguish between relapse and recurrence. Some studies which purported to be of prophylaxis were in effect only examining the continuation phase of acute treatment.

A review of treatment trials with DTγE revealed widely discrepant results. Relevant variables were the variety of measures employed for monitoring psychotic symptoms, and the different criteria used to judge the degree of improvement. The authors suggest a uniform outcome criterion for early trials of new treatments, which would generate more consistent and comparable results between studies, and give a stronger indication of the value of the treatment under test. When the data from the various treatment trials of DTγE were re analysed, applying a uniform outcome criterion of improvement of a change of 80% or more on rating-scale score, the results were more consistent than would have been suspected from the original reports.

Of twelve patients consecutively admitted to the Maudsley Hospital Eating Disorders Unit, four had neuromuscular abnormality, eight haematological abnormality, and four no abnormality. All those having neuromuscular signs had concomitant haematological dysfunction. Vomiting, and food restriction with vegetarianism, appeared more likely to lead to complications than either food restriction alone or laxative abuse. The physical status of severely underweight patients admitted for refeeding needs to be carefully monitored.

A recently proposed relationship between intropunitiveness and depressive states was examined in interview intervention with parasuicidal in-patients. To test the prediction that highly intropunitive parasuicidal individuals would be most responsive to cognitive intervention, a sample of 48 parasuicidal in-patients were administered a battery of individual difference measures, including the Hostility Questionnaire. Subjects were randomly assigned to one of three interview procedures, namely a cognitive interview, an affective interview or a waiting period (control). Highly intropunitive individuals in the cognitive interview group showed the most improvements on a self-report depressive symptom change measure. In addition to supporting theoretical models of depressive state changes, the study has important clinical implications because of the need to identify parasuicidal individuals who are most likely to benefit from brief interventions.

The hypothesis that schizophrenia is a recent disease can explain why descriptions of schizophrenia-like disorders were rare before 1800, why the prevalence of insanity in the Western world increased during the 19th but remained low in the non-Western world until the 20th century, and why schizophrenia has become milder in the West during recent decades. It also explains why schizophrenia has ‘persisted’ in spite of its associated low fertility. The evidence for the hypothesis is somewhat frail, but perhaps not more so than that for alternative hypotheses.

“The good doctor can no longer be content without this knowledge – that his object is not only to save a life, but also to make the life he saves worth living” (Vasicka et al, 1958). This concept was being put forward 30 years ago by an American doctor, Vasicka, and his colleagues working in a gynaecological tumour clinic.

Family history was examined to determine whether suicide in index patients is associated with suicidal behaviour or mental disorder in their first-degree relatives. Twenty-seven suicides occurred within 5½ years among 955 affectively disordered probands. Among 5042 proband relatives aged 18 years and older, 44 had committed suicide prior to proband entry to the study; however, only one was the relative of a proband suicide. Only two of the relatives who committed suicide were themselves related. As to attempted suicide of relatives, neither the number of attempts nor the severity of attempt was predictive of suicide in probands. Comparison of diagnosis between groups of relatives showed more drug abuse among relatives of proband suicides; this appears to be related to drug abuse among the proband suicides themselves. In contrast to the clustering of suicides within biological families found in other research, these data do not support the use of family history as a clinically useful indicator of suicidal potential in affectively disordered probands.

Transcutaneous carbon dioxide monitoring has been used to investigate directly the frequency and role of hyperventilation during naturally occurring panic attacks in freely ambulant volunteers and patients. Illustrative preliminary data from healthy subjects and from four patients with panic attacks are presented. These confirm that some patients do hyperventilate during their attacks but indicate that some do not. The unreliability of traditional methods for identifying hyperventilators is demonstrated. These data indicate the potential of ambulant monitoring in research into hyperventilation and panic.

Schizophrenic patients were recruited into a trial of a prophylactic behavioural intervention with families. Families with at least one high Expressed Emotion (EE) relative were randomly allocated to one of four intervention groups: Behavioural Intervention Enactive; Behavioural Intervention Symbolic; Education Only; Routine Treatment. Patients from low-EE families were randomly allocated to two groups: Education Only or Routine Treatment. Relapse rates over nine months after discharge were significantly lower for patients in the two Behavioural Intervention, compared with Education Only and Routine Treatment groups. There was little difference between the two low-EE groups. Patients returning to high-EE relatives showed significantly higher relapse rates than those returning to low-EE relatives, in groups not receiving active intervention. Changes from high to low EE occurred in the Behavioural Intervention groups, and similar although less extensive changes occurred in the Education Only and Routine Treatment groups. Changes in criticism and marked emotional over-involvement (EOI) occurred generally in high-EE groups but were larger in magnitude in the Enactive and Symbolic groups. Reduction of hostility only occurred in the Behavioural Intervention groups. These results give partial support for the causal role of EE in relapse. There were no significant differences between the groups with respect to contact with the psychiatric services or medication.

The literature indicates that whether or not schizophrenic patients are reported to have significant lateral ventricular enlargement depends on control, and not schizophrenic-group values. This discrepancy does not result from differences in age, the ratio of males to females, the number of control subjects used in each study, or whether control groups are comprised of normal subjects or medical patients. However, medical-patient controls tend to have smaller ventricles than do normal individuals. Thus, we assessed lateral-and third-ventricle size and the degree of cortical atrophy in 30 normal volunteers, 30 medical patients, and 30 chronic schizophrenic patients. The use of a medical control group seemed to result in underestimates of ventricle and sulcal size in the normal population and, therefore, overestimates of these values in schizophrenic groups.

Previously, the addition of lithium to haloperidol has been reported to be of modest benefit to schizoaffective patients. To test this treatment on a different sample, 36 mainly schizophrenic patients were subdivided on the basis of the median of their initial depression score on the BPRS into depressive and non-depressive schizophrenic subjects. Each group randomly received haloperidol plus placebo or haloperidol plus lithium for 8 weeks. The schizophrenic patients who were on the depressive side of the median BPRS depression score were found to be the most resistant to neuroleptic treatment alone, and benefited from the addition of lithium.

Plasma renin activity (PRA), aldosterone (aldo) levels, electrolyte levels, and blood pressures were measured in 16 patients with affective disorders taking lithium prophylactically, and in 16 age and sex-matched control subjects. PRA and aldo levels were significantly elevated in the lithium-treated group. There was no difference between the groups in plasma electrolytes or erect and supine blood pressures, arguing against secondary aldosteronism. In the lithium-treated group, there was a significant positive correlation between both PRA and plasma aldo vs serum lithium. We postulate that lithium inhibits the action of aldosterone on the distal tubule in the kidney. Activation of the renin angiotensin system maintains normal blood pressure and plasma electrolytes.

Fluoxetine is a new antidepressant agent which is a selective inhibitor of neuronal serotonin uptake; it has minimal affinity for muscarinic, dopaminergic, histaminic, serotonergic, or noradrenergic receptors (Stark et al, 1985). This specificity of activity suggests that fluoxetine may have a side-effect profile which is different from previously available antidepressants.

The safety of fluoxetine has been extensively studied: several hundred patients have received the drug continuously for more than one year - some have had therapy for 5 years or more. Previous reviews of the safety of fluoxetine (Wernicke, 1985; Zerbe, 1986) have described a smaller population of patients than is now available.

This review is drawn from data pooled from comparative clinical trials, which included 4336 patients: fluoxetine - 2938, tricyclic antidepressants (TCAs) - 599, and placebo - 799 patients. The TCAs studied were amitriptyline, imipramine, and doxepin. Most patients were adults with major depressive disorder, and the most common study design was a 6-week comparative double-blind phase, followed by unblinded long-term treatment. While the core of this study is a data base of 2938 fluoxetine-treated patients, all serious adverse events reported in over 7500 fluoxetine-treated patients worldwide, as of mid-1987, have been included.

Antidepressants are associated with a variety of side-effects, ranging in severity from the merely annoying to those with significant morbidity and even potential mortality. Prominent among the latter are cardiovascular effects, which have provided much of the impetus for the development of newer antidepressants such as fluoxetine. In this paper, we will review these cardiovascular effects, but as this has been previously undertaken elsewhere (e.g. Glassman & Bigger, 1981; Marshall & Forker, 1882; Glassman, 1984a), our consideration will be selective, with emphasis on methodological issues of relevance to the evaluation of new antidepressants. Since mechanisms of cardiac side-effects are best understood in relation to tricyclic antidepressants (TCAs), these will be a major focus, and will provide a background for the consideration of newer agents.

While less is known regarding the side-effects of the newer antidepressants, examination of the evolution of knowledge and opinions regarding their safety is particularly pertinent in that it illustrates the waxing and waning of enthusiasm that typically accompanies the introduction of new therapeutic agents. We review below the growing body of data regarding fluoxetine and some of the other serotonin-selective antidepressants, as well as discussing serotonergic effects on the cardiovascular system and their implications for the clinical use of these agents. Since the interactions between antidepressants and drugs used to treat cardiovascular disorders have been reviewed by Risch et al (1982) and Glassman & Salzman (1987), these will not be considered here.

Twenty-nine overweight schizophrenic patients maintained on depot neuroleptic injections who wished to lose weight took part in a double-blind, placebo-controlled trial of 30 mg d-fenfluramine. All subjects received dietary advice. Sixteen patients completed the 12-week trial. Rate of weight loss was significantly greater in those taking d-fenfluramine. Side-effects were reported, but no deterioration in mental state was noted.

The sensations produced were those of exquisite lightness and airiness … I expected to be lifted up and carried away by the first breeze … the walls of my frame were burst outward and tumbled into ruin, and without thinking what form I wore … I felt that I existed throughout a vast extent of space. The blood pulsed from my head, sped through uncounted leagues before it reached my extremities; the air drawn into my lungs expanded into seas of limpid ether, and the arch of my skull was broader than the vault of heaven … I was a mass of transparent jelly, and a confectioner poured me into a twisted mould. (Taylor, 1856)

Although the incidence of the recurrent psychoses (bipolar affective illness and schizophrenia) in the two sexes is approximately equal, gender influences a number of aspects of major psychiatric disease: unipolar depressive illness is twice as common in females, onset of schizophrenia is earlier and outcome is worse in males, and pairs of psychotic first-degree relatives are more often than expected of the same sex. In addition, sex chromosomal aneuploidies (e.g. XXY and XXX) are more frequent in patients with psychosis. Some of these findings can be explained if there is a major locus of predisposition to psychiatric disease in the ‘pseudoautosomal’ region of the sex chromosomes – that distal segment of the short arms in which there is genetic exchange between X and Y chromosomes at male meiosis. A gene located here would be transmitted in an autosomal manner, but would be passed above chance expectation to children of the same sex when inherited through a male. In that this segment of the sex chromosomes is subject to a high rate of recombination (which could generate new mutations), and may include determinants of brain lateralisation, it appears that the pseudoautosomal region could carry the genes which predispose to the major psychoses.