Antipsychotic medication for people with first episode schizophrenia: an exploratory economic analysis of alternative treatment algorithms

Available clinical evidence suggests that the newer antipsychotics are similar to conventional antipsychotics for positive symptom control. It has been suggested that they may also be superior for negative symptoms and side effects, but the evidence for this is unclear (Duggan et al, 1999, Kennedy et al, 1999, Srisurapanont et al, 1999, Thornley et al, 1999, Tuunainen and Gilbody, 1999, Wahlbeck et al, 1999). These differences if they exist, may lead to improvements in quality of life and patient satisfaction and subsequent rates of compliance with therapy. If the latter occurs, there may also be improvements in the overall level of symptom control and rate of relapse. Economic evaluations of risperidone suggest that these differences could lead to savings in the use of hospital inpatient care compared to conventional antipsychotics (Guest et al, 1996, Glennie, 1997). The available economic evidence suggests that the use of clozapine has the potential to improve the efficient use of health and social service resources in some patients (Revicki et al, 1990, Davies & Drummond, 1993, Meltzer et al, 1993, Aitchison & Kerwin, 1997, Glennie, 1997, Rosenheck et al, 1997). All of these studies indicate that overall, clozapine is associated with lower rates of hospital inpatient admissions and lower duration of inpatient stay. These are due to earlier discharge from the index inpatient admission and lower rates of relapse. These differences in the use of inpatient care are sufficient to offset the additional costs of purchasing clozapine. However, the designs of all the economic studies raise several issues of concern, such as control for biases, sources of data and methods of data collection, measurement of outcomes, the type and dose regimes of comparator drugs. In addition, the clinical and economic data for these evaluations were collected for a patient population with a long duration of illness and/or who are treatment resistant or intolerant of typical antipsychotic therapy. It is not clear that these are applicable to people with early schizophrenia or those who have not had problems with previous antipsychotics. Patients currently categorised as treatment resistant or treatment intolerant are likely to have a long history of schizophrenia. This is partly due to historical factors, such as the limited number of antipsychotics available, concerns about the safety of clozapine and the restricted use of expensive atypical antipsychotics. These factors may be associated with a relatively poor quality of life and more intensive use of health care services in patients with a longer duration of illness. Any improvements in clinical outcome as a result of a change in antipsychotic may also result in relatively important changes in health status and intensity of ealth service utilisation, compared to those with a recent diagnosis of schizophrenia. In addition, there is some limited evidence that the use of services following entry to a clinical trial is related to the level of resource use prior to entry (Rosenheck et al, 1999). Furthermore, there is a trend to reduce reliance on inpatient or institutional care for people with acute or chronic mental illness. The total number of commissioned hospital bed days for people with mental illness decreased from 14 million to 11.5 million between 1992-3 and 1997-8 and the number of ward attendees fell from 124000 to 93000 (Department of Health, 1998a). Over the same period the number of daily available hospital beds for people with mental illness declined from 47000 to 37000, while the number of outpatient attendances rose from 1.8 million to 2.1 million (HPSS, 1998). Creed et al (1997) suggest that approximately 40% of people with acute episodes of mental illness (including schizophrenia) can be treated by attending psychiatric day hospitals rather then with hospital inpatient admissions. These factors may over estimate the likely value for money of the atypical antipsychotics, in cohorts of people with first episode schizophrenia in the current UK mental health service (Rosenheck et al, 1999). Given the constraints on health and social care budgets, purchasers and providers need to ensure that resources are used efficiently. A variety of guidelines and treatment protocols have been published, or developed for use at a local level to support decisions about the choice of antipsychotic for people with a first episode of schizophrenia. In addition, there are wide variations in the availability and use of the atypical antipsychotics in the UK. Current published literature is not sufficient to address all the economic issues of concern and there is a need for evaluation of the relative efficiency of clozapine and the new antipsychotics. The NHS R&D HTA has funded primary research to assess the relative costs and utility of typical and atypical antipsychotics for people who are resistant to or intolerant of at least two antipsychotics. However, the results of the research will not be available for at least 3 years. In addition, it is also important to assess the value of the new drugs in the context of alternative prescribing guidelines, and for people with a first episode of schizophrenia. This paper presents the results of secondary research to explore the potential economic impact of atypical antipsychotics for people in the context of current clinical guidelines.schizophrenia, QALYs

Schizotypy and psychosis-like experiences from recreational cannabis in a non-clinical sample

Background. The relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use. Method. In a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the psychometric properties of the CEQ. Results. We replicated our previously reported findings that schizotypy was associated with increased psychosis-like experiences and after-effects, but also found that high-scoring schizotypes reported more pleasurable experiences when smoking cannabis. Using new subscales derived from principal components analysis (PCA), we found that the psychosis-like items were most related to varying rates of schizotypy both during the immediate use of cannabis and in the after-effects of cannabis use. High-scoring schizotypes who used cannabis experienced more psychosis-like symptoms during and after use.Conclusions. Our results suggest that cannabis use may reveal an underlying vulnerability to psychosis in those with high schizotypal traits

Endophytic bacterial diversity in the phyllosphere of Amazon Paullinia cupana associated with asymptomatic and symptomatic anthracnose

Background Acting on harmful command hallucinations is a major clinical concern. Our COMMAND CBT trial approximately halved the rate of harmful compliance (OR = 0.45, 95% CI 0.23–0.88, p = 0.021). The focus of the therapy was a single mechanism, the power dimension of voice appraisal, was also significantly reduced. We hypothesised that voice power differential (between voice and voice hearer) was the mediator of the treatment effect. Methods The trial sample (n = 197) was used. A logistic regression model predicting 18-month compliance was used to identify predictors, and an exploratory principal component analysis (PCA) of baseline variables used as potential predictors (confounders) in their own right. Stata's paramed command used to obtain estimates of the direct, indirect and total effects of treatment. Results Voice omnipotence was the best predictor although the PCA identified a highly predictive cognitive-affective dimension comprising: voices’ power, childhood trauma, depression and self-harm. In the mediation analysis, the indirect effect of treatment was fully explained by its effect on the hypothesised mediator: voice power differential. Conclusion Voice power and treatment allocation were the best predictors of harmful compliance up to 18 months; post-treatment, voice power differential measured at nine months was the mediator of the effect of treatment on compliance at 18 months

The COMMAND trial of cognitive therapy for harmful compliance with command hallucinations (CTCH) : a qualitative study of acceptability and tolerability in the UK

Objectives To explore service user experiences of a 9-month cognitive behavioural therapy for command hallucinations in the context of a randomised controlled trial including their views on acceptability and tolerability of the intervention. Design Qualitative study using semistructured interviews. Setting The study took place across three sites: Birmingham, Manchester and London. Interviews were carried out at the sites where therapy took place which included service bases and participants’ homes. Participants Of 197 patients who consented to the trial, 98 received the Cognitive Behavior Therapy for Command Hallucinations (CTCH) intervention; 25 (15 males) of whom were randomly selected and consented to the qualitative study. The mean age of the sample was 42 years, and 68% were white British. Results Two superordinate themes were identified: participants’ views about the aspects of CTCH they found most helpful; and participants’ concerns with therapy. Helpful aspects of the therapy included gaining control over the voices, challenging the power and omniscience of the voices, following a structured approach, normalisation and mainstreaming of the experience of voices, and having peer support alongside the therapy. Concerns with the therapy included anxiety about completing CTCH tasks, fear of talking back to voices, the need for follow-up and ongoing support and concerns with adaptability of the therapy. Conclusions Interpretation: CTCH was generally well received and the narratives validated the overall approach. Participants did not find it an easy therapy to undertake as they were challenging a persecutor they believed had great power to harm; many were concerned, anxious and occasionally disappointed that the voices did not disappear altogether. The trusting relationship with the therapist was crucial. The need for continued support was expressed

Integrating mobile-phone based assessment for psychosis into people\u27s everyday lives and clinical care: a qualitative study

Background: Over the past decade policy makers have emphasised the importance of healthcare technology in the management of long-term conditions. Mobile-phone based assessment may be one method of facilitating clinically- and cost-effective intervention, and increasing the autonomy and independence of service users. Recently, text-message and smartphone interfaces have been developed for the real-time assessment of symptoms in individuals with schizophrenia. Little is currently understood about patients\u27 perceptions of these systems, and how they might be implemented into their everyday routine and clinical care. Method: 24 community based individuals with non-affective psychosis completed a randomised repeated-measure cross-over design study, where they filled in self-report questions about their symptoms via text-messages on their own phone, or via a purpose designed software application for Android smartphones, for six days. Qualitative interviews were conducted in order to explore participants\u27 perceptions and experiences of the devices, and thematic analysis was used to analyse the data. Results: Three themes emerged from the data: i) the appeal of usability and familiarity, ii) acceptability, validity and integration into domestic routines, and iii) perceived impact on clinical care. Although participants generally found the technology non-stigmatising and well integrated into their everyday activities, the repetitiveness of the questions was identified as a likely barrier to long-term adoption. Potential benefits to the quality of care received were seen in terms of assisting clinicians, faster and more efficient data exchange, and aiding patient-clinician communication. However, patients often failed to see the relevance of the systems to their personal situations, and emphasised the threat to the person centred element of their care. Conclusions: The feedback presented in this paper suggests that patients are conscious of the benefits that mobile-phone based assessment could bring to clinical care, and that the technology can be successfully integrated into everyday routine. However, it also suggests that it is important to demonstrate to patients the personal, as well as theoretical, benefits of the technology. In the future it will be important to establish whether clinical practitioners are able to use this technology as part of a personalised mental health regime

Culturally-adapted Family Intervention (CaFI) for African-Caribbeans diagnosed with schizophrenia and their families : a feasibility study protocol of implementation and acceptability

Background African-Caribbeans in the UK have the highest schizophrenia incidence and greatest inequity in access to mental health services of all ethnic groups. The National Institute for Health and Care Excellence (NICE) highlights this crisis in care and urgent need to improve evidence-based mental healthcare, experiences of services and outcomes for this group. Family intervention (FI) is clinically and cost-effective for the management of schizophrenia but it is rarely offered. Evidence for FI with minority ethnic groups generally, and African-Caribbeans in particular, is lacking. This study aims to test the feasibility and acceptability of delivering Culturally-adapted Family Intervention (CaFI) to African-Caribbean service users diagnosed with schizophrenia. Methods/Design This is a feasibility cohort design study. Over a 12-month intervention period, 30 service users and their families, recruited from hospital and community settings, will receive ten one-hourly sessions of CaFI. Where biological families are absent, access to the intervention will be optimised through ‘family support members’; trusted individuals nominated by service users or study volunteers. We shall collect data on eligibility, uptake, retention and attrition and assess the utility and feasibility of collecting various outcome measures including readmission, service engagement, working alliance, clinical symptoms and functioning, perceived criticism, psychosis knowledge, familial stress and economic costs. Measures will be collected at baseline, post-intervention and at 3-month follow-up using validated questionnaires and standardised interviews. Admission rates and change in care management will be rated by independent case note examination. Variability in the measures will inform sample size estimates for a future trial. Independent raters will assess fidelity to the intervention in 10 % of sessions. Feedback at the end of each session along with thematically-analysed qualitative interviews will examine CaFI’s acceptability to service users, families and healthcare professionals. Discussion This innovative response to inequalities in mental healthcare experienced by African-Caribbeans diagnosed with schizophrenia might improve engagement in services, access to evidence-based interventions and clinical outcomes. Successful implementation of CaFI in this group could pave the way for better engagement and provision across marginalised groups and therefore has potentially important implications for commissioning and service delivery in ethnically diverse populations. This study will demonstrate whether the approach is feasible and acceptable and can be implemented with fidelity in different settings

Treatment resistance NMDA receptor pathway polygenic score is associated with brain glutamate in schizophrenia

Dysfunction of glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia and may be particularly relevant in severe, treatment-resistant symptoms. The underlying mechanism may involve hypofunction of the NMDA receptor. We investigated whether schizophrenia-related pathway polygenic scores, composed of genetic variants within NMDA receptor encoding genes, are associated with cortical glutamate in schizophrenia. Anterior cingulate cortex (ACC) glutamate was measured in 70 participants across 4 research sites using Proton Magnetic Resonance Spectroscopy (1H-MRS). Two NMDA receptor gene sets were sourced from the Molecular Signatories Database and NMDA receptor pathway polygenic scores were constructed using PRSet. The NMDA receptor pathway polygenic scores were weighted by single nucleotide polymorphism (SNP) associations with treatment-resistant schizophrenia, and associations with ACC glutamate were tested. We then tested whether NMDA receptor pathway polygenic scores with SNPs weighted by associations with non-treatment-resistant schizophrenia were associated with ACC glutamate. A higher NMDA receptor complex pathway polygenic score was significantly associated with lower ACC glutamate (β = −0.25, 95 % CI = −0.49, −0.02, competitive p = 0.03). When SNPs were weighted by associations with non-treatment-resistant schizophrenia, there was no association between the NMDA receptor complex pathway polygenic score and ACC glutamate (β = 0.05, 95 % CI = −0.18, 0.27, competitive p = 0.79). These results provide initial evidence of an association between common genetic variation implicated in NMDA receptor function and ACC glutamate levels in schizophrenia. This association was specific to when the NMDA receptor complex pathway polygenic score was weighted by SNP associations with treatment-resistant schizophrenia