Metabolism of clozapine is complex and not fully understood. Pharmacokinetic interactions with other drugs have been described but, in some cases, their mechanism is unknown.

Published trials and case reports relevant to the human metabolism of clozapine and to suspected pharmacokinetic interactions were reviewed.

Metabolism of clozapine appears to be largely controlled by the function of the hepatic cytochrome p4501A2 (CYPIA2). Compounds which induce CYPIA2 activity (carbamazepine, tobacco smoke) may reduce plasma clozapine levels. Inhibitors of CYPIA2 (caffeine, erythromycin) have the opposite effect. Drugs which inhibit the hepatic cytochrome p4502D6 (CYP2D6) have also been reported to elevate plasma clozapine levels. The mechanism of this interaction is unclear.

The co-administration of clozapine and compounds reported to alter its metabolism should be avoided where possible. A host of other interactions can be predicted and so caution should be exercised when co-administering drugs which affect the function of CYPIA2 and CYP2D6. The pharmacokinetics of clozapine require further investigation so that its safe use can be assured.

Schizophrenia is highly expensive in calculable and incalculable costs. Measures which impact the cost in the most severely affected are likely to produce the greatest cost reductions. Studies regarding clozapine in the USA have demonstrated clear cost-effectiveness, despite the high prescription costs. There are no prior UK studies.

We performed a cost-effectiveness analysis comparing the three years prior to commencing clozapine to the period following establishment of clozapine treatment (mean 36.4 months) for 26 patients with chronic schizophrenia or schizoaffective disorder.

There was a significant improvement in all clinical ratings applied (and a mean net saving of £3768 per annum). The cost-effectiveness of clozapine was double that of conventional neuroleptics (15.2 pre-, 33.0 post-clozapine, P < 0.005).

As a naturalistic study our data provide valuable information on the cost-effectiveness of clozapine in the UK. Our methodology could be applied in a community setting or in the study of another atypical neuroleptic.

The consensus statement on the treatment of depression (Paykel & Priest, 1992) advocates the use of cognitive therapy techniques as an adjunct to medication.

This paper describes a randomised controlled trial of brief cognitive therapy (BCT) plus ‘treatment as usual’ versus treatment as usual in the management of 48 patients with major depressive disorder presenting in primary care.

At the end of the acute phase, significantly more subjects (P < 0.05) met recovery criteria in the intervention group (n=15) compared with the control group (n=8). When initial neuroticism scores were controlled for, reductions in Beck Depression Inventory and Hamilton Rating Scale for Depression scores favoured the BCT group throughout the 12 months of follow-up.

BCT may be beneficial, but given the time constraints, therapists need to be more rather than less skilled in cognitive therapy. This, plus methodological limitations, leads us to advise caution before applying this approach more widely in primary care.

Exposure and response prevention is considered a treatment of choice for obsessive–compulsive disorder (OCD). Yet there have been very few randomised controlled trials employing credible placebo conditions. This study compares exposure and response prevention with a general anxiety management intervention.

Eighteen patients meeting DSM–IV criteria for OCD were randomly assigned to either exposure and response prevention or anxiety management. Both treatments involved approximately 15 hours of therapy over a three-week period.

There was a significant reduction in obsessive–compulsive symptoms following treatment with exposure and response prevention, while no change occurred in the control group. This was found to be statistically significant using a composite measure of OCD symptom severity, patient ratings of interference and therapist ratings of symptom severity.

These findings suggest that the symptom reductions associated with behaviour therapy for OCD are a result of the specific techniques of exposure and response prevention, rather than non-specific aspects of the therapy process. General anxiety management techniques are not effective in the treatment of OCD.

Several studies have reported a decline of up to 50% in the incidence of schizophrenia over recent decades. We aimed to measure changes in the incidence and diagnostic patterns of first-episode psychosis by comparing two Nottingham cohorts, identified in two equal periods separated by 14 years.

Two prospectively ascertained cohorts of first-episode psychotic disorder were identified over the time periods 1978–80 and 1992–94. The earlier cohort was of the World Health Organization Determinants of Outcome of Severe Mental Disorder (DOSMD) ten-country study. The later cohort was obtained using similar methodology. Both groups were diagnosed using ICD-10 diagnostic criteria and age-standardised incidence rates were compared.

The standardised incidence rate for all psychotic disorders rose slightly from 2.49 to 2.87 per 10 000 population per year, but the F20 classification fell significantly by over a third (1.41 to 0.87 per 10 000 per year). The second study group (1992–1994) included a greater diversity of psychotic diagnoses compared with the first, in particular an increased proportion of acute and drug-related psychoses.

Methodological considerations call for caution in interpreting such data, but we conclude that the significant fall in the narrowly defined diagnostic category of schizophrenia reflects a real change in the syndromal presentation of psychotic disorders.

It has been suggested that the increased rate of psychotic illness among African–Caribbeans living in Britain is due to an excess of pregnancy and birth complications (PBCs).

We therefore compared the frequency of PBCs in a group of White psychotic patients (n=103) and a comparable group of patients of African–Caribbean origin (n=61); the latter consisted of 30 first-generation (born in the Caribbean) and 31 second-generation (born in Britain) individuals.

White psychotic patients were more than twice as likely to have a history of PBCs as their African–Caribbean counterparts (odds ratio=2.34, 95% confidence interval (CI) 0.88–6.47, P=0.062). The same trend was observed among patients with a DSM–III diagnosis of schizophrenia (odds ratio=l.65, 95% CI 0.56–4.97, P=0.32). The rate of PBCs was similar among the first- and second-generation Caribbean psychotic patients.

The increased rate of psychotic illness that has been reported among the African–Caribbean population in Britain is not due to an increased prevalence of PBCs.

Severe tardive dyskinesia (TD) represents a serious and potentially disabling movement disorder, yet relatively little is known about the incidence of and risk factors for severeTD.

We report the results of a longitudinal prospective incidence study of severeTD in 378 middle-aged and elderly neuropsychiatric patients. Psychiatric, neuropsychological, pharmacological and motor variables were obtained at intake and at regular intervals for 36 months.

The cumulative incidence of severeTD was 2.5% after one year, 12.1% after two years, and 22.9% after three years. Individual univariable Cox regression analyses were conducted to identify demographic, psychiatric, motor and pharmacological predictors of severeTD. Results indicated that higher daily doses of neuroleptics at study entry, greater cumulative amounts of prescribed neuroleptic, and greater severity of worsening negative symptoms were predictive of severeTD Conclusions These findings suggest that conventional neuroleptics may be prescribed to older patients only when necessary and at the lowest effective dosage. Additional caution is recommended in patients exhibiting negative symptoms.

While executive (frontal lobe) dysfunction appears to be a core feature of schizophrenia, its relationship to psychopathology, age and duration of illness has yet to be explored systematically between the genders.

Executive dysfunction, positive and negative symptoms were evaluated in 27 male and 21 female in-patients who were unusually well-matched on numerous demographic and clinical measures.

Measures of executive dyscontrol and negative symptoms were highly associated in both genders. However, while both executive dyscontrol and negative symptoms increased prominently with age/duration of illness among women, no such relationship was evident among men.

The similarly prominent levels of current executive dyscontrol and negative symptoms in male and female patients appear to have emerged via processes that differ fundamentally between the genders; among males these deficits appear to emerge and become ‘locked in’ earlier in the course of illness and to show little subsequent increase, while among females these same deficits appear to be less evident early in the course but to increase in prominence thereafter.

The aim of this study was to provide information on patients' current service use which could inform future decisions on service planning and resource allocation.

Individuals with a diagnosis of schizophrenia, who had received in-patient care in the previous five years, were identified from the Lothian Case Register. Information was obtained from 193 subjects. Patients' service use over a six-month period was examined. The costs incurred in service provision were determined.

Patients differed markedly in their use of services. This was not found to be related to their mental state. Average care costs were high. In-patient care accounted for most of the overall expenditure.

There is considerable variation in the services used by patients with schizophrenia and in the costs incurred in service provision. When planning services it is therefore important that detailed information on the patient population is available if resources are to be allocated cost-effectively.

This second report of a study of service provision for patients with schizophrenia describes patients' contact with general practice and general practitioners' (GPs’) views of the mental health services.

A postal questionnaire was sent to the GPs, and patients' primary care records were examined.

Data were collected on 131 subjects. The majority of patients (96) (73%) were in regular contact with their GP and were consulting for many different reasons; 27 (21%) were posing particular difficulties for the primary care team. GPs reported that 27 (21%) patients required additional support and that the care arrangements for 50 (38%) patients could be improved if alterations were made to the roles of the professionals already involved.

GPs are central to service provision for patients with schizophrenia. Both additional resources and changes in working practices are required to improve patient care. The service implications of these findings are discussed.

Communication between secondary and primary care is an important aspect of continuity of care. We investigated communication between general practitioners (GPs) and psychiatric teams about a representative group of patients with severe mental illness (SMI). We also sought views on GP involvement in care from the patients and their GPs.

One hundred patients with SMI were randomly selected from those under the care of two psychiatric sector teams in inner London. The patients and their GPs were interviewed.

GPs' knowledge about the care their patients received was limited. Most GPs perceived their role as providing physical care and prescribing. Few patients consulted GPs for mental health care. GPs perceived themselves as less involved in the care of Black Caribbean or Black African patients.

Considerable discontinuities of care between secondary and primary care were identified. GP involvement in the care of patients with SMI appears limited. Better communication is necessary if care is to be shared.

This paper describes severe, disorders of maternal affection and behaviour and suggests that there is an early process of mother-to-infant bonding which can go seriously wrong.

Forty-four self-selected women who had suffered from at least one episode of postnatal mental illness described an unexpected and often catastrophic failure to love one or more of their babies.

These women reported absent affection, sometimes hate, rejection, neglect or impulses to harm, in relation to at least one of their children. These feelings often began immediately or very shortly after the birth, and with one exception, were specific to one child; such characteristics are best encapsulated by the term ‘maternal bonding disorder’. Twenty-nine of the women were multiparae; first-borns were not significantly more likely to be the focus for such feelings. There was no direct evidence of predisposing maternal personality traits or previous experiences. Postnatal mental illness and recalled severe pain during labour were significantly associated with such disorders which, in their severe forms, did not occur in the absence of postnatal mental illness.

The nature of the link between postnatal mental illness and disorders of maternal bonding remains unclear. Because, in multiparae, the disorder often ‘missed’ the first child, factors such as maternal personality traits or early childhood experiences cannot be regarded as sufficient causes.

Abnormalities of catecholaminergic function have been hypothesised to cause depressive illness. Plasma noradrenaline can be used as a marker of central noradrenergic activity. It is of interest to examine the change in resting plasma noradrenaline in patients with depressive illness over a course of electroconvulsive therapy (ECT) and relate this to their clinical state.

Patients referred for ECT who suffered from DSM – III – R major depressive disorder or dysthymia were recruited. Blood samples were taken before and after each treatment, during a course of ECT, to measure plasma noradrenaline and Cortisol. Clinical ratings were carried out weekly during the course of ECT.

Plasma noradrenaline fell significantly in those patients with melancholic/psychotic depressions but increased in those with non-melancholic depressive illness. There was a strong trend indicating that a fall in plasma noradrenaline was associated with improvement in depression ratings in the melancholic/psychotic patients only.

Electroconvlusive therapy decreases plasma noradrenaline in melancholic/psychotic depressive illness and this shows a trend associated with clinical improvement.