CLEAR - clozapine in early psychosis: study protocol for a multi-centre, randomised controlled trial of clozapine vs other antipsychotics for young people with treatment resistant schizophrenia in real world settings.

BACKGROUND: Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. METHODS AND DESIGN: This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12-24 years old). AIM AND OBJECTIVES: The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. DISCUSSION: The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. TRIAL REGISTRATION: ISRCTN Number: 37176025, IRAS Number: 1004947. TRIAL STATUS: In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

Impact of hospitalisation on the outcome of adolescent anorexia nervosa.

BACKGROUND: Owing to the lack of controlled trials of treatment setting in adolescent anorexia nervosa, the benefits and costs of in-patient treatment are not established. AIMS: To clarify the relationship between a range of presenting features, treatment received and medium- to long-term outcome in adolescent anorexia nervosa. METHOD: A range of presenting variables were rated for 75 cases of DSM-III-R anorexia nervosa at presentation to an adolescent service, including the Morgan-Russell Global Assessment Score. Cases were followed up at 2-7 years and outcome rated according to reliable methods. Setting of treatment received was also recorded. RESULTS: Two out of 75 cases had died by the time of follow-up. Adequate data for 72 enabled an outcome category to be assigned. The 21 who had received inpatient treatment had a significantly worse outcome than the 51 never admitted to hospital. Multivariate analysis suggests admission to be the major predictor of poor outcome. CONCLUSIONS: The benefits and costs of admission to hospital require further investigation, ideally in a randomised-controlled trial. The negative consequences of in-patient treatment are neglected in research.

Attitudes to people with mental handicap.

Nurses working with mentally handicapped people may have much to learn from the work and theories of social psychologists. Ron Elvins' wide-ranging article explores some of these theories and looks at how prejudices arise; examples from socio-psychological research serve as illustrations of the problems which integration of population groups present, and perhaps offer models of how integration can be successfully facilitated.