The role of psychosis and clozapine load in excessive checking in treatment-resistant schizophrenia: longitudinal observational study.

BACKGROUND: A significant proportion of people with clozapine-treated schizophrenia develop 'checking' compulsions, a phenomenon yet to be understood. AIMS: To use habit formation models developed in cognitive neuroscience to investigate the dynamic interplay between psychosis, clozapine dose and obsessive-compulsive symptoms (OCS). METHOD: Using the anonymised electronic records of a cohort of clozapine-treated patients, including longitudinal assessments of OCS and psychosis, we performed longitudinal multi-level mediation and multi-level moderation analyses to explore associations of psychosis with obsessiveness and excessive checking. Classic bivariate correlation tests were used to assess clozapine load and checking compulsions. The influence of specific genetic variants was tested in a subsample. RESULTS: A total of 196 clozapine-treated individuals and 459 face-to-face assessments were included. We found significant OCS to be common (37.9%), with checking being the most prevalent symptom. In mediation models, psychosis severity mediated checking behaviour indirectly by inducing obsessions (r = 0.07, 95% CI 0.04-0.09; P < 0.001). No direct effect of psychosis on checking was identified (r = -0.28, 95% CI -0.09 to 0.03; P = 0.340). After psychosis remission (n = 65), checking compulsions correlated with both clozapine plasma levels (r = 0.35; P = 0.004) and dose (r = 0.38; P = 0.002). None of the glutamatergic and serotonergic genetic variants were found to moderate the effect of psychosis on obsession and compulsion (SLC6A4, SLC1A1 and HTR2C) survived the multiple comparisons correction. CONCLUSIONS: We elucidated different phases of the complex interplay of psychosis and compulsions, which may inform clinicians' therapeutic decisions.

Clozapine-related obsessive-compulsive symptoms and their impact on wellbeing: a naturalistic longitudinal study.

BACKGROUND: Obsessive-compulsive symptoms (OCS) are commonly associated with clozapine treatment but are frequently overlooked by clinicians despite their potential impact on patients' quality of life. In this study, we explored whether OCS severity impacted subjective wellbeing and general functioning, independently of depressive and psychotic symptoms. METHODS: We used anonymised electronic healthcare records from a large cohort of patients who were treated with clozapine and assessed annually for OCS, wellbeing, general functioning, and psychopathology using standardised scales as part of routine clinical practice. We used statistical mixed linear model techniques to evaluate the longitudinal influence of OCS severity on wellbeing and general functioning. RESULTS: A total of 184 patients were included, with 527 face-to-face assessments and 64.7% evaluated three or more times. Different linear mixed models demonstrated that OCS in patients treated with clozapine were associated with significantly worse wellbeing scores, independently of depression and psychotic symptoms, but OCS did not impair general functioning. Obsessional thinking and hoarding behaviour, but not compulsions, were significantly associated with the impact on wellbeing, which may be attributable to the ego-syntonic nature of the compulsions. CONCLUSIONS: Given the frequent occurrence of OCS and their negative impact on wellbeing, we encourage clinicians to routinely assess and treat OCS in patients who are taking clozapine.

The Early Youth Engagement in first episode psychosis (EYE-2) study: pragmatic cluster randomised controlled trial of implementation, effectiveness and cost-effectiveness of a team-based motivational engagement intervention to improve engagement.

BACKGROUND: Early Intervention in Psychosis (EIP) services improve health outcomes for young people with psychosis in the medium-long term, but 25% of young people disengage in the first 12 months with costs to their mental health, families, society and the NHS. This study will evaluate the effectiveness, cost-effectiveness and implementation of a team-based motivational Early Youth Engagement (EYE-2) intervention. METHOD: The study design is a cluster randomised controlled trial (RCT) with economic evaluation, comparing the EYE-2 intervention + standardised EIP service to standardised EIP service alone, with randomisation at the team level. A process evaluation will evaluate the delivery of the intervention qualitatively and quantitatively across contexts. The setting is 20 EIP teams in 5 sites: Manchester, South London, East Anglia, Thames Valley and Hampshire. Participants are young people (14-35 years) with first episode psychosis, and EIP staff. The intervention is the team-based motivational engagement (EYE-2) intervention, delivered alongside standardised EIP services, and supported by additional training, website, booklets and social groups. The comparator is the standardised EIP service. Both interventions are delivered by EIP clinicians. The primary outcome is time to disengagement (time in days from date of allocation to care coordinator to date of last contact following refusal to engage with EIP service, or lack of response to EIP contact for a consecutive 3-month period). Secondary outcomes include mental and physical health, deaths, social and occupational function, recovery, satisfaction and service use at 6, 12, 18 and 24 months. A 12-month within-trial economic evaluation will investigate cost-effectiveness from a societal perspective and from an NHS perspective. DISCUSSION: The trial will provide the first test of an engagement intervention in standardised care, with the potential for significant impact on the mental health and wellbeing of young people and their families, and economic benefits for services. The intervention will be highly scalable, supported by the toolkit including manuals, commissioning guide, training and resources, adapted to meet the needs of the diverse EIP population, and based on an in-depth process evaluation. TRIAL REGISTRATION: ISRCTN 51629746 prospectively registered 7th May 2019. Date assigned 10th May 2019.

Multilevel ordinal factor analysis of the positive and negative syndrome scale (PANSS).

Clinical assessments of the presence and severity of psychopathology are often collected by health care professionals in mental health services or clinical researchers trained to use semi-structured interviews. Clustering by interviewer or rater needs to be considered when performing psychometric analyses such as factor analysis or item response modelling as non-independence of observations arises in these situations. We apply more suitable multilevel methods to analyse ordinally scored Positive and Negative Syndrome Scale (PANSS) items. Our aim is to highlight the differences in results that occur when the data are analysed using a hierarchically sensitive approach rather than using a traditional (aggregated) analysis. Our sample (n = 507) consisted of patients diagnosed with schizophrenia who participated in a multi-centre randomized control clinical trial, the DIALOG study. Analyses reported and compared include an exploratory factor analysis as well as several recently published multifactor models re-estimated within a confirmatory analysis framework. Our results show that the fit of the model and the parsimony of the exploratory factor analysis (EFA) models indicated by the number of factors necessary to explain the inter-correlation among PANSS items improved significantly when data clustering is taken into account through multilevel analysis. Our modeling results support the pentagonal PANSS model first proposed by White et al. (1997). Copyright © 2014 John Wiley & Sons, Ltd.

Young people's views of UK mental health services.

AIMS AND METHOD: Adolescence is the period of highest risk for the development of mental illness, but also the age group least likely to seek help from mental health services. We undertook a systematic review of the published literature on the views of young people of mental health services in the UK and a thematic analysis of the findings to explore the reasons behind this to guide those developing services for young people. RESULTS: Thirty-one studies were identified, which captured the views of 13 605 young people including 625 young people who had experience of mental health services. Positive views to emerge were of qualities of mental health workers and encouraging self-reliance. Negative views were of stigma, lack of information, medicalization of their problems and a lack of continuity of care. CONCLUSIONS: Young people have consistent views of the positive and negative aspects of mental health services, which could be helpfully incorporated in the design of services. The views of some groups of young people have not been well represented, however, and the views of minority ethnic groups and those who have disengaged from services in particular need to be actively sought.