Identifying types of problems and relative priorities in the problem lists of participants in CBT for psychosis trials.

BACKGROUND: There is wide variation in the problems prioritised by people with psychosis in cognitive behavioural therapy for psychosis (CBTp). While research trials and mental health services have often prioritised reduction in psychiatric symptoms, service users may prioritise issues not directly related to psychosis. This discrepancy suggests potential challenges in treatment outcome research. AIMS: The present study aimed to examine the types of problems that were recorded on problem lists generated in CBTp trials. METHOD: Problem and goals lists for 110 participants were extracted from CBTp therapy notes. Subsequently, problems were coded into 23 distinct categories by pooling together items that appeared thematically related. RESULTS: More than half of participants (59.62%) listed a non-psychosis-related priority problem, and 22.12% did not list any psychosis related problems. Chi-square tests indicated there was no difference between participants from early intervention (EI) and other services in terms of priority problem (χ2 = 0.06, p = .804), but that those from EI were more likely to include any psychosis-related problems in their lists (χ2 = 6.66, p = .010). CONCLUSIONS: The findings of this study suggest that psychiatric symptom reduction is not the primary goal of CBTp for most service users, particularly those who are not under the care of EI services. The implications for future research and clinical practice are discussed.

Adapting cognitive behavioural therapy for adolescents with psychosis: insights from the Managing Adolescent first episode in psychosis study (MAPS).

Background: Onset of psychosis commonly occurs in adolescence, and long-term prognosis can be poor. There is growing evidence, largely from adult cohorts, that Cognitive Behavioural Therapy for Psychosis (CBTp) and Family Interventions (FI) can play a role in managing symptoms and difficulties associated with psychosis. However, adolescents have distinct developmental needs that likely impact their engagement and response to talking therapy. There is limited guidance on adapting CBTp to meet the clinical needs of under-eighteens experiencing psychosis. Method: This educational clinical practice article details learnings from therapists and supervisors working with young people (aged 14-18 years) with psychosis during the Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) randomised clinical treatment trial, supplemented by findings from nested qualitative interviews with young people receiving CBTp. Results: Suggested are given for tailoring CBTp assessment, formulation and interventions to meet the developmental and clinical needs of adolescents with psychosis. Developmentally appropriate techniques and resources described. Conclusions: Early indications from MAPS study indicate this developmentally tailored approach is an acceptable, safe and helpful treatment for young people with psychosis. Further research is needed to develop empirically grounded and evaluated CBTp for adolescents.

A psychological intervention for engaging dialogically with auditory hallucinations (Talking With Voices): A single-site, randomised controlled feasibility trial.

There is growing clinical interest in addressing relationship dynamics between service-users and their voices. The Talking With Voices (TwV) trial aimed to establish feasibility and acceptability of a novel dialogical intervention to reduce distress associated with voices amongst adults diagnosed with schizophrenia spectrum disorders. The single-site, single-blind (rater) randomised controlled trial recruited 50 participants who were allocated 1:1 to treatment as usual (TAU), or TAU plus up to 26 sessions of TwV therapy. Participants were assessed at baseline and again at end of treatment (six-months). The primary outcomes were quantitative and qualitative assessments of feasibility and acceptability. Secondary outcomes involved clinical measures, including targeted instruments for voice-hearing, dissociation, and emotional distress. The trial achieved 100 % of the target sample, 24 of whom were allocated to therapy and 26 to TAU. The trial had high retention (40/50 [80 %] participants at six-months) and high intervention adherence (21/24 [87.5 %] receiving ≥8 sessions). Signals of efficacy were shown in targeted measures of voice-hearing, dissociation, and perceptions of recovery. Analysis on the Positive and Negative Syndrome Scale indicated that there were no differences in means of general psychosis symptom scores in TwV compared to the control group. There were four serious adverse events in the therapy group and eight in TAU, none of which were related to study proceedings. The trial demonstrates the acceptability of the intervention and the feasibility of delivering it under controlled, randomised conditions. An adequately powered definitive trial is necessary to provide robust evidence regarding efficacy evaluation and cost-effectiveness. Trial registration: ISRCTN 45308981.

Multisite randomised controlled trial of trauma-focused cognitive behaviour therapy for psychosis to reduce post-traumatic stress symptoms in people with co-morbid post-traumatic stress disorder and psychosis, compared to treatment as usual: study protocol for the STAR (Study of Trauma And Recovery) trial.

BACKGROUND: People with psychosis have high rates of trauma, with a post-traumatic stress disorder (PTSD) prevalence rate of approximately 15%, which exacerbates psychotic symptoms such as delusions and hallucinations. Pilot studies have shown that trauma-focused (TF) psychological therapies can be safe and effective in such individuals. This trial, the largest to date, will evaluate the clinical effectiveness of a TF therapy integrated with cognitive behaviour therapy for psychosis (TF-CBTp) on post-traumatic stress symptoms in people with psychosis. The secondary aims are to compare groups on cost-effectiveness; ascertain whether TF-CBTp impacts on a range of other meaningful outcomes; determine whether therapy effects endure; and determine acceptability of the therapy in participants and therapists. METHODS: Rater-blind, parallel arm, pragmatic randomised controlled trial comparing TF-CBTp + treatment as usual (TAU) to TAU only. Adults (N = 300) with distressing post-traumatic stress and psychosis symptoms from five mental health Trusts (60 per site) will be randomised to the two groups. Therapy will be manualised, lasting 9 months (m) with trained therapists. We will assess PTSD symptom severity (primary outcome); percentage who show loss of PTSD diagnosis and clinically significant change; psychosis symptoms; emotional well-being; substance use; suicidal ideation; psychological recovery; social functioning; health-related quality of life; service use, a total of four times: before randomisation; 4 m (mid-therapy); 9 m (end of therapy; primary end point); 24 m (15 m after end of therapy) post-randomisation. Four 3-monthly phone calls will be made between 9 m and 24 m assessment points, to collect service use over the previous 3 months. Therapy acceptability will be assessed through qualitative interviews with participants (N = 35) and therapists (N = 5-10). An internal pilot will ensure integrity of trial recruitment and outcome data, as well as therapy protocol safety and adherence. Data will be analysed following intention-to-treat principles using generalised linear mixed models and reported according to Consolidated Standards of Reporting Trials-Social and Psychological Interventions Statement. DISCUSSION: The proposed intervention has the potential to provide significant patient benefit in terms of reductions in distressing symptoms of post-traumatic stress, psychosis, and emotional problems; enable clinicians to implement trauma-focused therapy confidently in this population; and be cost-effective compared to TAU through reduced service use. TRIAL REGISTRATION: ISRCTN93382525 (03/08/20).

A treatment protocol to guide the delivery of dialogical engagement with auditory hallucinations: Experience from the Talking With Voices pilot trial.

PURPOSE: To present a treatment protocol for delivering Talking With Voices, a novel intervention for people with psychosis that involves dialogical engagement with auditory hallucinations. METHOD: This paper presents a manualized approach to therapy employed in the Talking With Voices trial, a feasibility and acceptability randomized control trial of 50 adult participants. A rationale for following a treatment manual is provided, followed by the theoretical underpinnings of the intervention and its principles and values, including the main tenet that voices can often be understood as dissociated parts of the self which serve a protective function by indicating social-emotional vulnerabilities. The four therapy phases for improving the relationship between the voice-hearer and their voices are outlined: (1) engagement and psychoeducation, (2) creating a formulation, (3) dialoguing with voices, and (4) consolidating outcomes, including key milestones at each phase. Implementation issues are discussed, as well as recommendations for best practice and future research. RESULTS: The Talking With Voices treatment protocol indicates that it is feasible to manualize a dissociation-based approach to support service users who are distressed by hearing voices. CONCLUSION: For some individuals, it is possible to engage in productive dialogue with even extremely hostile or distressing voices. Developing coping strategies, creating a formulation, and ultimately establishing a dialogue with voices has the potential to improve the relationship between voice(s) and voice-hearer. Further research is now required to evaluate feasibility, acceptability, and efficacy. PRACTITIONER POINTS: It is feasible to integrate a dissociation model of voice-hearing within a psychological intervention for people with psychosis. Combining psychosocial education, formulation and direct dialogue can be used to facilitate a more peaceful relationship between clients and their voices. Practitioners trained in other therapeutic modalities can draw on existing transferrable skills to dialogue with their clients' voices. The input of those with lived experience of mental health difficulties has an important role in guiding treatment design and delivery.

Psychological intervention, antipsychotic medication or a combined treatment for adolescents with a first episode of psychosis: the MAPS feasibility three-arm RCT.

BACKGROUND: When psychosis emerges in young people there is a risk of poorer outcomes, and access to evidence-based treatments is paramount. The current evidence base is limited. Antipsychotic medications show only a small benefit over placebo, but young people experience more side effects than adults. There is sparse evidence for psychological intervention. Research is needed to determine the clinical effectiveness and cost-effectiveness of psychological intervention versus antipsychotic medication versus a combined treatment for adolescents with psychosis. OBJECTIVES: The objective of Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS) was to determine the feasibility of conducting a definitive trial to answer the question of clinical effectiveness and cost-effectiveness of these three treatment options. DESIGN: This was a prospective, randomised, open-blinded, evaluation feasibility trial with a single blind. Participants were allocated 1 : 1 : 1 to receive antipsychotic medication, psychological intervention or a combination of both. A thematic qualitative study explored the acceptability and feasibility of the trial. SETTING: Early intervention in psychosis services and child and adolescent mental health services in Manchester, Oxford, Lancashire, Sussex, Birmingham, Norfolk and Suffolk, and Northumberland, Tyne and Wear. PARTICIPANTS: People aged 14-18 years experiencing a first episode of psychosis either with an International Classification of Diseases, Tenth Revision, schizophrenia spectrum diagnosis or meeting the entry criteria for early intervention in psychosis who had not received antipsychotic medication or psychological intervention within the last 3 months. INTERVENTIONS: Psychological intervention involved up to 26 hours of cognitive-behavioural therapy and six family intervention sessions over 6 months, with up to four booster sessions. Antipsychotic medication was prescribed by the participant's psychiatrist in line with usual practice. Combined treatment was a combination of psychological intervention and antipsychotic medication. MAIN OUTCOME MEASURES: The primary outcome was feasibility (recruitment, treatment adherence and retention). We used a three-stage progression criterion to determine feasibility. Secondary outcomes were psychosis symptoms, recovery, anxiety and depression, social and educational/occupational functioning, drug and alcohol use, health economics, adverse/metabolic side effects and adverse/serious adverse events. RESULTS: We recruited 61 out of 90 (67.8%; amber zone) potential participants (psychological intervention, n = 18; antipsychotic medication, n = 22; combined treatment, n = 21). Retention to follow-up was 51 out of 61 participants (83.6%; green zone). In the psychological intervention arm and the combined treatment arm, 32 out of 39 (82.1%) participants received six or more sessions of cognitive-behavioural therapy (green zone). In the combined treatment arm and the antipsychotic medication arm, 28 out of 43 (65.1%) participants received antipsychotic medication for 6 consecutive weeks (amber zone). There were no serious adverse events related to the trial and one related adverse event. Overall, the number of completed secondary outcome measures, including health economics, was small. LIMITATIONS: Medication adherence was determined by clinician report, which can be biased. The response to secondary outcomes was low, including health economics. The small sample size obtained means that the study lacked statistical power and there will be considerable uncertainty regarding estimates of treatment effects. CONCLUSIONS: It is feasible to conduct a trial comparing psychological intervention with antipsychotic medication and a combination treatment in young people with psychosis with some adaptations to the design, including adaptations to collection of health economic data to determine cost-effectiveness. FUTURE WORK: An adequately powered definitive trial is required to provide robust evidence. TRIAL REGISTRATION: Current Controlled Trials ISRCTN80567433. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 4. See the NIHR Journals Library website for further project information.

Psychosis is a mental health problem that can involve hearing, seeing or believing things that others do not. Although many young people who experience psychosis recover well from their first episode of psychosis, others can have more serious, longer-lasting problems. There has not been a large amount of research into the treatment of psychosis in young people; therefore, it is important to test different treatments against each other in clinical trials. 'Feasibility' trials, such as the one we carried out [Managing Adolescent first-episode Psychosis: a feasibility Study (MAPS)], test whether or not it is possible to run larger trials. MAPS was a small trial that was run in seven locations in the UK. People who were aged 14­18 years and experiencing psychosis were able to take part. Each participant was randomly assigned to receive psychological treatment (cognitive­behavioural therapy and optional family therapy), antipsychotic medication or a combination of both. All of the participants met with a trial research assistant three times for assessments about well-being and symptoms. Some clinicians, participants and family members were interviewed about their opinions of the trial and treatments. The trial also had patient and public involvement; service user researchers were involved in design, interview data collection, analysis and report writing. Sixty-one young people took part in MAPS, which was around 68% of our target number. In total, 84% completed the assessments with research assistants. The results showed that, overall, all treatments were acceptable to young people and their family members. However, a higher percentage of young people actually received the 'minimum dose' of psychological treatment than the 'minimum dose' of antipsychotic medication (82% vs. 65%). Results showed that it was possible to run a larger trial such as this. However, some changes would be required to run a larger trial, such as location (focusing on urban areas with well established early intervention in psychosis teams), increasing involvement of psychiatrists and increasing the age limit for participation to 25 years.

Targeting dissociation using cognitive behavioural therapy in voice hearers with psychosis and a history of interpersonal trauma: A case series.

OBJECTIVES: Previous studies have suggested that dissociation might represent an important mechanism in the maintenance of auditory verbal hallucinations (i.e., voices) in people who have a history of traumatic life experiences. This study investigated whether a cognitive behavioural therapy (CBT) intervention for psychosis augmented with techniques specifically targeting dissociative symptoms could improve both dissociation and auditory hallucination severity in a sample of voice hearers with psychosis and a history of interpersonal trauma (e.g., exposure to sexual, physical, and/or emotional abuse). DESIGN: Case series. METHODS: A total of 19 service users with psychosis were offered up to 24 therapy sessions over a 6-month intervention window. Participants were assessed four times over a 12-month period using measures of dissociation, psychotic symptoms severity, and additional secondary mental-health and recovery measures. RESULTS: Sixteen participants engaged in the intervention and were included in last-observation-carried-forward analyses. Dropout rates were in line with those of other CBT for psychosis trials (26.3%). Repeated measures ANOVAs revealed large and significant improvements in dissociation (drm  = 1.23) and hallucination severity (drm  = 1.09) by the end of treatment; treatment gains were maintained 6 months following the end of therapy. Large and statistically significant gains were also observed on measures of post-traumatic symptoms, delusion severity, emotional distress, and perceived recovery from psychosis. CONCLUSIONS: The findings of this case series suggest that the reduction of dissociation represents a valuable and acceptable treatment target for clients with auditory verbal hallucinations and a trauma history. Future clinical trials might benefit from considering targeting dissociative experiences as part of psychological interventions for distressing voices. PRACTITIONER POINTS: Practitioners should consider the role of dissociation when assessing and formulating the difficulties of voice hearers with a history of trauma. Techniques to reduce dissociation can be feasibly integrated within psychological interventions for voices. Voice hearers with histories of trauma can benefit from psychological interventions aimed at reducing dissociation.

A guide to behavioural experiments in bipolar disorder.

Behavioural experiments are an important component of cognitive-behavioural therapy. However, there exists little up-to-date guidance on how to conduct these in people with a diagnosis of bipolar disorder. This paper provides recommendations on how to conduct behavioural experiments in this population. The aim is to upskill and empower clinicians to conduct behavioural experiments. The paper combines the expertise of senior clinicians working in the United Kingdom. The article starts by providing general advice on conducting behavioural experiments in people with bipolar disorder. It then offers specific examples of behavioural experiments targeting cognitions around the uncontrollability and danger of affective states, and related behavioural strategies, which have been implicated in the maintenance of bipolar mood swings. The article finishes by providing examples of behavioural experiments for non-mood related difficulties that commonly occur with bipolar experiences including perfectionistic thinking, need for approval, and intrusive memories. Behavioural experiments offer a useful therapeutic technique for instigating cognitive and behavioural change in bipolar disorder. Conducted sensitively and collaboratively, in line with people's recovery-focused goals, behavioural experiments can be used to overcome mood- and non-mood related difficulties.

Cognitive-behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT.

BACKGROUND: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of cognitive-behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. DESIGN: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). SETTING: Secondary care mental health services in five cities in the UK. PARTICIPANTS: People with CRS aged ≥ 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. INTERVENTIONS: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. MAIN OUTCOME MEASURES: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. RESULTS: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) -3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (-2.40 points, 95% CI -4.79 to -0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI -£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). CONCLUSIONS: Cognitive-behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99672552. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 7. See the NIHR Journals Library website for further project information.

Metacognitive Therapy for Individuals at High Risk of Developing Psychosis: A Pilot Study.

Developing effective interventions for preventing first episode psychosis have been an important research focus in the last decade. Cognitive behavioral therapy is a currently indicated treatment for people at ultra-high risk of psychosis, however, access and resource issues limit its delivery within the NHS. Treatments which partial out potential active ingredients and are aimed at a range of psychological difficulties seen within this population have the potential to be more efficacious and efficient. We conducted a single-arm exploratory pilot trial, designed to investigate the feasibility and acceptability of Metacognitive therapy for individuals at ultra-high risk (UHR) of developing psychosis. Trial uptake was good, with 11 out of 12 referred individuals meeting for an eligibility assessment (one individual was excluded prior to the assessment). Of these, 10 individuals were eligible and included in the trial. Retention to treatment was high with 80% treatment adherence gained and an overall average of 8 sessions completed. All participants were offered follow-up assessments immediately post-treatment and at 6 months, which comprised measures of psychotic like experiences, anxiety and depression, and metacognitive processes implicated in the model. Retention to the post-treatment (12-week) follow-up was good, with 80% completion; however retention to the 6-month follow-up was lower at 60%. Clinically significant results were observed in psychotic like experiences, anxiety, depression and functioning with medium to large effect sizes. Measures related to beliefs and processes targeted within MCT showed clinically significant change with medium to large effect sizes. Our results suggest that MCT based upon a specific metacognitive model for individuals meeting ARMS criteria may be an important treatment target and warrants further attention. Limitations and possible focuses for future research are discussed. Registration: ISRCTN53190465 http://www.isrctn.com/ISRCTN53190465.

Cognitive behavioural therapy in clozapine-resistant schizophrenia (FOCUS): an assessor-blinded, randomised controlled trial.

BACKGROUND: Although clozapine is the treatment of choice for treatment-refractory schizophrenia, 30-40% of patients have an insufficient response, and others are unable to tolerate it. Evidence for any augmentation strategies is scarce. We aimed to determine whether cognitive behavioural therapy (CBT) is an effective treatment for clozapine-resistant schizophrenia. METHODS: We did a pragmatic, parallel group, assessor-blinded, randomised controlled trial in community-based and inpatient mental health services in five sites in the UK. Patients with schizophrenia who were unable to tolerate clozapine, or whose symptoms did not respond to the drug, were randomly assigned 1:1 by use of randomised-permuted blocks of size four or six, stratified by centre, to either CBT plus treatment as usual or treatment as usual alone. Research assistants were masked to allocation to protect against rater bias and allegiance bias. The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months, which provides a continuous measure of symptoms of schizophrenia; PANSS total was also assessed at the end of treatment (9 months). The primary analysis was by randomised treatment based on intention to treat, for all patients for whom data were available. This study was prospectively registered, number ISRCTN99672552. The trial is closed to accrual. FINDINGS: From Jan 1, 2013, to May 31, 2015, we randomly assigned 487 participants to either CBT and treatment as usual (n=242) or treatment as usual alone (n=245). Analysis included 209 in the CBT group and 216 in the treatment as usual group. No difference occurred in the primary outcome (PANSS total at 21 months, mean difference -0·89, 95% CI -3·32 to 1·55; p=0·48), although the CBT group improved at the end of treatment (PANSS total at 9 months, mean difference -2·40, -4·79 to -0·02; p=0·049). During the trial, 107 (44%) of 242 participants in the CBT arm and 104 (42%) of 245 in the treatment as usual arm had at least one adverse event (odds ratio 1·09, 95% CI 0·81 to 1·46; p=0·58). Only two (1%) of 242 participants in the CBT arm and one (<1%) of 245 in the treatment as usual arm had a trial-related serious adverse event. INTERPRETATION: At 21-month follow-up, CBT did not have a lasting effect on total symptoms of schizophrenia compared with treatment as usual; however, CBT produced statistically, though not clinically, significant improvements on total symptoms by the end of treatment. There was no indication that the addition of CBT to treatment as usual caused adverse effects. The results of this trial do not support a recommendation to routinely offer CBT to all people who meet criteria for clozapine-resistant schizophrenia; however, a pragmatic individual trial might be indicated for some. FUNDING: National Institute for Health Research Technology Assessment programme.

Antipsychotic drugs versus cognitive behavioural therapy versus a combination of both in people with psychosis: a randomised controlled pilot and feasibility study.

BACKGROUND: Little evidence is available for head-to-head comparisons of psychosocial interventions and pharmacological interventions in psychosis. We aimed to establish whether a randomised controlled trial of cognitive behavioural therapy (CBT) versus antipsychotic drugs versus a combination of both would be feasible in people with psychosis. METHODS: We did a single-site, single-blind pilot randomised controlled trial in people with psychosis who used services in National Health Service trusts across Greater Manchester, UK. Eligible participants were aged 16 years or older; met ICD-10 criteria for schizophrenia, schizoaffective disorder, or delusional disorder, or met the entry criteria for an early intervention for psychosis service; were in contact with mental health services, under the care of a consultant psychiatrist; scored at least 4 on delusions or hallucinations items, or at least 5 on suspiciousness, persecution, or grandiosity items on the Positive and Negative Syndrome Scale (PANSS); had capacity to consent; and were help-seeking. Participants were assigned (1:1:1) to antipsychotics, CBT, or antipsychotics plus CBT. Randomisation was done via a secure web-based randomisation system (Sealed Envelope), with randomised permuted blocks of 4 and 6, stratified by gender and first episode status. CBT incorporated up to 26 sessions over 6 months plus up to four booster sessions. Choice and dose of antipsychotic were at the discretion of the treating consultant. Participants were followed up for 1 year. The primary outcome was feasibility (ie, data about recruitment, retention, and acceptability), and the primary efficacy outcome was the PANSS total score (assessed at baseline, 6, 12, 24, and 52 weeks). Non-neurological side-effects were assessed systemically with the Antipsychotic Non-neurological Side Effects Rating Scale. Primary analyses were done by intention to treat; safety analyses were done on an as-treated basis. The study was prospectively registered with ISRCTN, number ISRCTN06022197. FINDINGS: Of 138 patients referred to the study, 75 were recruited and randomly assigned-26 to CBT, 24 to antipsychotics, and 25 to antipsychotics plus CBT. Attrition was low, and retention high, with only four withdrawals across all groups. 40 (78%) of 51 participants allocated to CBT attended six or more sessions. Of the 49 participants randomised to antipsychotics, 11 (22%) were not prescribed a regular antipsychotic. Median duration of total antipsychotic treatment was 44·5 weeks (IQR 26-51). PANSS total score was significantly reduced in the combined intervention group compared with the CBT group (-5·65 [95% CI -10·37 to -0·93]; p=0·019). PANSS total scores did not differ significantly between the combined group and the antipsychotics group (-4·52 [95% CI -9·30 to 0·26]; p=0·064) or between the antipsychotics and CBT groups (-1·13 [95% CI -5·81 to 3·55]; p=0·637). Significantly fewer side-effects, as measured with the Antipsychotic Non-neurological Side Effects Rating Scale, were noted in the CBT group than in the antipsychotics (3·22 [95% CI 0·58 to 5·87]; p=0·017) or antipsychotics plus CBT (3·99 [95% CI 1·36 to 6·64]; p=0·003) groups. Only one serious adverse event was thought to be related to the trial (an overdose of three paracetamol tablets in the CBT group). INTERPRETATION: A head-to-head clinical trial of CBT versus antipsychotics versus the combination of the two is feasible and safe in people with first-episode psychosis. FUNDING: National Institute for Health Research.

Design and protocol for the Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial: a randomised controlled trial.

BACKGROUND: For around a third of people with a diagnosis of schizophrenia, the condition proves to respond poorly to treatment with many typical and atypical antipsychotics. This is commonly referred to as treatment-resistant schizophrenia. Clozapine is the only antipsychotic with convincing efficacy for people whose symptoms are considered treatment-resistant to antipsychotic medication. However, 30-40 % of such conditions will have an insufficient response to the drug. Cognitive behavioural therapy has been shown to be an effective treatment for schizophrenia when delivered in combination with antipsychotic medication, with several meta-analyses showing robust support for this approach. However, the evidence for the effectiveness of cognitive behavioural therapy for people with a schizophrenia diagnosis whose symptoms are treatment-resistant to antipsychotic medication is limited. There is a clinical and economic need to evaluate treatments to improve outcomes for people with such conditions. METHODS/DESIGN: A parallel group, prospective randomised, open, blinded evaluation of outcomes design will be used to compare a standardised cognitive behavioural therapy intervention added to treatment as usual versus treatment as usual alone (the comparator group) for individuals with a diagnosis of schizophrenia for whom an adequate trial of clozapine has either not been possible due to tolerability problems or was not associated with a sufficient therapeutic response. The trial will be conducted across five sites in the United Kingdom. DISCUSSION: The recruitment target of 485 was achieved, with a final recruitment total of 487. This trial is the largest definitive, pragmatic clinical and cost-effectiveness trial of cognitive behavioural therapy for people with schizophrenia whose symptoms have failed to show an adequate response to clozapine treatment. Using a prognostic risk model, baseline information will be used to explore whether there are identifiable subgroups for which the treatment effect is greatest. TRIAL REGISTRATION: Current Controlled Trials ISRCTN99672552 . Registered 29(th) November 2012.

Cognitive therapy for internalised stigma in people experiencing psychosis: A pilot randomised controlled trial.

We aimed to evaluate the feasibility of Cognitive Therapy (CT) as an intervention for internalised stigma in people with psychosis. We conducted a single-blind randomised controlled pilot trial comparing CT plus treatment as usual (TAU) with TAU only. Participants were assessed at end of treatment (4 months) and follow-up (7 months). Twenty-nine participants with schizophrenia spectrum disorders were randomised. CT incorporated up to 12 sessions over 4 months (mean sessions=9.3). Primary outcome was the Internalised Stigma of Mental Illness Scale - Revised (ISMI-R) total score, which provides a continuous measure of internalised stigma associated with mental health problems. Secondary outcomes included self-rated recovery, internalised shame, emotional problems, hopelessness and self-esteem. Recruitment rates and retention for this trial were good. Changes in outcomes were analysed following the intention-to-treat principle, using ANCOVAs adjusted for baseline symptoms. There was no effect on our primary outcome, with a sizable reduction observed in both groups, but several secondary outcomes were significantly improved in the group assigned to CT, in comparison with TAU, including internalised shame, hopelessness and self-rated recovery. Stigma-focused CT appears feasible and acceptable in people with psychosis who have high levels of internalised stigma. A larger, definitive trial is required.

Prevalence of violence risk factors in people at ultra-high risk of developing psychosis: a service audit.

BACKGROUND: There is little data available on the prevalence of violence risk factors in people at ultra-high risk of developing psychosis. AIM: The aim of this study was to provide an estimate of the cross-sectional prevalence of violence risk factors in those attending a routine clinical service for people at ultra-high risk of developing psychosis. METHODS: The case notes of all 34 clients receiving treatment over a 4-week period were reviewed and all clinicians were interviewed. Information was gathered regarding gender, current violent ideation, history of violence (including convictions), expressions of concern from others, problems with alcohol or substance misuse, jealousy, suspiciousness, irritability, anger and relevant subthreshold psychotic symptoms. Information on protective factors, including treatment engagement, was also gathered. RESULTS: Thirty-eight per cent (n = 13) had a history of violent behaviour, 79.4% (n = 27) were thought to be currently experiencing significant levels of suspiciousness and 47.1% (n = 16) were thought to have problems with anger. Twenty-nine per cent (n = 10) had previous known convictions for violence. Two-thirds (n = 8) of those where risk of violence was identified were described as being engaged with treatment. CONCLUSION: There was a high prevalence of violence risk factors in this small sample. Further research with larger samples and better methodology is urgently required to investigate risk of violence in this group and determine the contribution, if any, of subclinical psychotic symptoms.

Prevalence of suicide risk factors in people at ultra-high risk of developing psychosis: a service audit.

BACKGROUND: Little data is available on the prevalence of suicide risk factors in people at ultra-high risk (UHR) of developing psychosis. AIM: The aim of this study was to provide an estimate of the cross-sectional prevalence of possible suicide risk factors in those attending a routine clinical service for people at UHR of developing psychosis. METHODS: For all patients in treatment (n=34) over a 4-week period, levels of suicidal ideation and depression upon entry to the service were assessed by auditing intake scores on the Beck Depression Inventory, second edition. Level of engagement with services, social isolation, substance and alcohol misuse, ready access to means, current suicidal ideation, previous suicide attempts, current or previous self-harm, expressions of concern from others, depression, agitation, hopelessness, worthlessness, suspiciousness and fears of mental disintegration were all assessed by case note review and interview with the treating clinician. RESULTS: There was a high prevalence of at least mild suicidal ideation (58.8%, n=20) and severe depressed mood (47%, n=16) in this client group at point of entry to the service. Seven people (20.6%) had engaged in serious self-harm (including attempted suicide) during the time they were in contact with the service. Forty-seven per cent (n=16) reported at least 27 suicide attempts between them; the mean number of attempts being 1.69 (standard deviation=1.08). CONCLUSION: Suicide risk was high in this small sample of people at UHR of developing psychosis. Controlled research with larger samples and better methodology is urgently required to inform legal, ethical and scientific debates surrounding this group.

Interpretations of voices in patients with hallucinations and non-patient controls: a comparison and predictors of distress in patients.

BACKGROUND: This study tested the hypotheses that interpretations of voices will be associated with distress linked to auditory hallucinations, and that patients experiencing hallucinations will exhibit higher levels of negative interpretations in comparison with non-patients. METHOD: The Interpretation of Voices Inventory (British Journal of Clinical Psychology 41 (2002) 259) was administered to patients who met DSM-IV criteria for schizophrenia spectrum disorders with auditory hallucinations and non-patients. Patients were also assessed using a semi-structured interview to asses clinical dimensions of their voices. RESULTS: The results showed that people with psychosis who experience auditory hallucinations did exhibit higher levels of positive and negative interpretations of voices, in comparison to non-patients. Correlational analyses revealed that interpretations of voices were significantly associated with emotional, physical and cognitive characteristics of voices. Regression analyses demonstrated that physical characteristics of voices and metaphysical beliefs were significant predictors of emotional characteristics of voices. CONCLUSIONS: The theoretical and clinical implications of these findings are discussed.