Treatment resistance causes significant burden in psychosis. Clozapine is the only evidence-based pharmacologic intervention available for people with treatment-resistant schizophrenia; current guidelines recommend commencement after two unsuccessful trials of standard antipsychotics.

This paper aims to explore the prevalence of treatment resistance and pathways to commencement of clozapine in UK early intervention in psychosis (EIP) services.

Data were taken from the National Evaluation of the Development and Impact of Early Intervention Services study (N = 1027) and included demographics, medication history and psychosis symptoms measured by the Positive and Negative Syndrome Scale (PANSS) at baseline, 6 months and 12 months. Prescribing patterns and pathways to clozapine were examined. We adopted a strict criterion for treatment resistance, defined as persistent elevated positive symptoms (a PANSS positive score ≥16, equating to at least two items of at least moderate severity), across three time points.

A total of 143 (18.1%) participants met the definition of treatment resistance of having continuous positive symptoms over 12 months, despite treatment in EIP services. Sixty-one (7.7%) participants were treatment resistant and eligible for clozapine, having had two trials of standard antipsychotics; however, only 25 (2.4%) were prescribed clozapine over the 12-month study period. Treatment-resistant participants were more likely to be prescribed additional antipsychotic medication and polypharmacy, instead of clozapine.

Prevalent treatment resistance was observed in UK EIP services, but prescription of polypharmacy was much more common than clozapine. Significant delays in the commencement of clozapine may reflect a missed opportunity to promote recovery in this critical period.

Social disability is a hallmark of severe mental illness yet individual differences and factors predicting outcome are largely unknown.

To explore trajectories and predictors of social recovery following a first episode of psychosis (FEP).

A sample of 764 individuals with FEP were assessed on entry into early intervention in psychosis (EIP) services and followed up over 12 months. Social recovery profiles were examined using latent class growth analysis.

Three types of social recovery profile were identified: Low Stable (66%), Moderate-Increasing (27%), and High-Decreasing (7%). Poor social recovery was predicted by male gender, ethnic minority status, younger age at onset of psychosis, increased negative symptoms, and poor premorbid adjustment.

Social disability is prevalent in FEP, although distinct recovery profiles are evident. Where social disability is present on entry into EIP services it can remain stable, highlighting a need for targeted intervention.

Early intervention services (EIS) comprise low-stigma, youth-friendly mental health teams for young people undergoing first-episode psychosis (FEP). Engaging with the family of the young person is central to EIS policy and practice.

By analysing carers' accounts of their daily lives and affective challenges during a relative's FEP against the background of wider research into EIS, this paper explores relationships between carers' experiences and EIS.

Semi-structured longitudinal interviews with 80 carers of young people with FEP treated through English EIS.

Our data suggest that EIS successfully aid carers to support their relatives, particularly through the provision of knowledge about psychosis and medications. However, paradoxical ramifications of these user-focused engagements also emerge; they risk leaving carers' emotions unacknowledged and compounding an existing lack of help-seeking.

By focusing on EIS's engagements with carers, this paper draws attention to an urgent broader question: as a continuing emphasis on care outside the clinic space places family members at the heart of the care of those with severe mental illness, we ask: who can, and should, support carers, and in what ways?

Interventions to reduce treatment delay in first-episode psychosis have met with mixed results. Systematic reviews highlight the need for greater understanding of delays within the care pathway if successful strategies are to be developed.

To document the care-pathway components of duration of untreated psychosis (DUP) and their link with delays in accessing specialised early intervention services (EIS). To model the likely impact on efforts to reduce DUP of targeted changes in the care pathway.

Data for 343 individuals from the Birmingham, UK, lead site of the National EDEN cohort study were analysed.

A third of the cohort had a DUP exceeding 6 months. The greatest contribution to DUP for the whole cohort came from delays within mental health services, followed by help-seeking delays. It was found that delay in reaching EIS was strongly correlated with longer DUP.

Community education and awareness campaigns to reduce DUP may be constrained by later delays within mental health services, especially access to EIS. Our methodology, based on analysis of care pathways, will have international application when devising strategies to reduce DUP.

None.

A major reason for interest in early intervention for psychotic disorders is the hypothesised relationship between longer duration of untreated psychosis (DUP) and poorer outcome of treatment.

To critically examine the evidence concerning DUP being related to treatment outcome and possible mediators of any such relationship.

A systematic review of studies in which DUP is assessed and its relationship to treatment outcome is examined. In addition, studies relevant to possible neurotoxic effects of DUP were reviewed.

The research is entirely of a correlational nature and, therefore, firm conclusions regarding causation are not possible. There is, however, substantial evidence of DUP being an independent predictor of treatment outcome, particularly remission of positive symptoms, over the first year or so of treatment. Findings regarding the possible neurotoxic effects of DUP are inconsistent.

There continues to be evidence consistent with DUP influencing aspects of treatment outcome. Non-correlational studies, such as quasi-experimental designs, could provide stronger evidence regarding causality.

A recent review suggested an association between using unpublished scales in clinical trials and finding significant results.

To determine whether such an association existed in schizophrenia trials.

Three hundred trials were randomly selected from the Cochrane Schizophrenia Group's Register. All comparisons between treatment groups and control groups using rating scales were identified. The publication status of each scale was determined and claims of a significant treatment effect were recorded.

Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison (relative risk 1.37 (95% C11.12–1.68)). This effect increased when a ‘gold-standard’ definition of treatment superiority was applied (RR 1.94 (95% C11.35–2.79)). In non-pharmacological trials, one-third of ‘gold-standard’ claims of treatment superiority would not have been made if published scales had been used.

Unpublished scales are a source of bias in schizophrenia trials.

Case management has become the statutory basis of community care in the UK for people with long-term mental disorders, although a randomised controlled trial found no important improvements over standard care. Here we compare the costs and cost consequences of this intervention with standard care.

Resource-use data were collected over a six-month baseline period and for 14 months after randomisation on all patients in the trial.

At 14 months the ratio of control group to treatment group weekly costs was 1.09 (95% CI 0.86–1.38) for total costs; 1.12 (0.76–1.65) for state benefits, and 1.21 (0.61–2.42) for health care costs. Costs were thus lower in the treatment group, but these differences were not significant.

Retrospective power calculations indicated that the trial could have detected differences of 30% in total cost, but would have required 700 patients per arm to detect a 20% difference in health care costs. Hence this study, which had adequate power to detect clinically meaningful differences, was found to be far too small to detect large differences in costs. Funding agencies increasingly request that clinical trials include economic alongside clinical end-points: these findings may have important lessons for that policy.