Discerning the adverse effects of psychological therapy: Consensus between experts by experience and therapists.

Measurement of adverse effects of psychological therapy is inconsistent due to ambiguity about the concept. The perspective of people undertaking psychological therapy (that is, experts by experience) has largely been overlooked. This study will investigate whether there is consensus between the opinions of professionals and experts by experience. The Delphi method was used. In Round 1 thematic analysis was used to analyse qualitative responses. Wilcoxon rank-sum tests were used to examine group differences in Rounds 2 and 3. The study protocol was prospectively registered, reference osf.io/f9wp7. Fifty-one professionals and 51 experts by experience generated 147 potential adverse effects in Round 1, across 9 themes; including 'therapy amplifies problem', 'emotional lability' and 'sense of self'. Each item was rated for overall consensus in Rounds 2 (n = 62) and 3 (n = 63). Thirty-eight items were rated as essential, very important or important to include on a list of potential adverse effects. A further 12 items were rated as important by the expert by experience group only. Professionals were more conservative in their ratings. There appeared to be consensus between professionals and experts by experience on what to include in a list of adverse effects of psychological therapy (the EDAPT), including novel adverse effects which have not been previously considered. Further research is required to understand which adverse effects are necessary, unnecessary, or indeed harmful to psychotherapy outcomes.

Decision-making ability in psychosis: a systematic review and meta-analysis of the magnitude, specificity and correlates of impaired performance on the Iowa and Cambridge Gambling Tasks.

To identify factors which may help or hinder decision-making ability in people with psychosis, we did a systematic review and meta-analysis of their performance on the Iowa and Cambridge Gambling Tasks. Analysis of 47 samples found they had moderately poorer performance than healthy individuals (N = 4264, g = -0.57, 95% confidence interval (CI) -0.66 to -0.48). Few studies (k = 8) used non-psychotic clinical comparator groups, although very low-quality evidence (k = 3) found people with bipolar disorder may perform better. Negative symptoms (k = 13, N = 648, r = -0.17, 95% CI -0.26 to -0.07) and lower IQ (k = 11, N = 525, r = 0.20, 95% CI 0.29-0.10), but not positive symptoms (k = 10, N = 512, r = -0.01, 95% CI -0.11 to 0.08), each had small-moderate associations with poorer decision-making. Lower quality evidence suggested general symptoms, working memory, social functioning, awareness of emotional responses to information, and attentional bias towards gain are associated with decision-making, but not education, executive functioning or overall symptoms. Meta-regression suggested an inverse association between decision-making and depression severity (k = 6, Q = 6.41, R2 100%, p = 0.01). Those taking first-generation (k = 6, N = 305, g = -0.17, 95% CI -0.40 to 0.06, p = 0.147) or low-dose antipsychotics (k = 5, N = 442, g = -0.19, 95% CI -0.44 to 0.06, p = 0.139) had unimpaired decision-making. Although meta-regression found no linear association between dose and performance, non-reporting of the dose was common and associated with larger impairments (k = 46, Q = 4.71, R2 14%, p = 0.03). Those supporting people with psychosis to make decisions, including treatment decisions, should consider the potential effect of these factors. Interventionist-causal trials are required to test whether reducing antipsychotic dose and treating anxiety and depression can improve decision-making in this group.

Psychological interventions for ICD-11 complex PTSD symptoms: systematic review and meta-analysis.

BACKGROUND: The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions. METHODS: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality. RESULTS: Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = -0.90 (CBT; k = 27, 95% CI -1.11 to -0.68; moderate quality) to g = -1.26 (EMDR; k = 4, 95% CI -2.01 to -0.51; low quality). CBT and EA each had moderate-large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate-large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome. CONCLUSIONS: The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences.

A feasibility study of a cross-diagnostic, CBT-based psychological intervention for acute mental health inpatients: Results, challenges, and methodological implications.

OBJECTIVES: Acute psychiatric inpatient wards are characterized by minimal provision of therapeutic activities and high readmission rates. Implementation of a comprehensive inpatient psychological intervention service has been recommended to overcome these problems; however, whether this is feasible or effective remains unclear. METHODS: This non-randomized parallel cluster feasibility trial examined the feasibility of delivering and evaluating cross-diagnostic psychologically informed acute psychiatric care the Edinburgh-Acute Psychological Inpatient Therapy Service (EDAPTS) and gathered preliminary clinical outcome data. Patients able to consent and complete questionnaires were recruited from two adult acute wards (i.e., clusters) and received either EDAPTS plus TAU or TAU. RESULTS: Between October 2015 and October 2016, 96 inpatients were recruited. Findings suggested that there were good data completion rates for several clinical outcomes, that several EDAPTS components were successfully delivered, and that some initial effects appeared to favour the intervention, depending on outcome. However, difficulties relating to the recruitment process were also identified, as well as problems relating to adequate delivery of group therapies, participant engagement in some intervention components, and data completion at follow-up. CONCLUSION: These issues, and the feasibility of randomization and rater-blinding, have important implications for the design of future trials. Overall, this study provides an important insight into the challenges and complexities of developing and evaluating a comprehensive psychological intervention service in an acute psychiatric setting. PRACTITIONER POINTS: Individual therapy sessions can be delivered in the acute environment. The EDAPTS intervention showed some promise on outcomes of distress and self-efficacy. Delivery of nurse-led groups was challenging and may need to be embedded into routine clinical practice to increase intervention and outcome reach. More parameters, for example, randomization at cluster level, should be tested before progressing to an adequately powered, single-blind, definitive cluster RCT.

Spontaneous CD4+ and CD8+ T-cell responses directed against cancer testis antigens are present in the peripheral blood of testicular cancer patients.

Cancer/testis antigen (CTAg) expression is restricted to spermatogenic cells in an immune-privileged site within the testis. However, these proteins are expressed aberrantly by malignant cells and T-cell responses against CTAgs develop in many cancer patients. We investigated the prevalence, magnitude and phenotype of CTAg-specific T cells in the blood of patients with testicular germ cell tumors (TGCTs). CD8+ and CD4+ T-cell responses against MAGE-A family antigens were present in 44% (20/45) of patients' samples assayed by ex vivo IFN-γ ELISPOT. The presence of MAGE-specific CD8+ T cells was further determined following short-term in vitro expansion through the use of pMHC-I multimers containing known immunogenic peptides. Longitudinal analysis revealed that the frequency of MAGE-specific T cells decreased by 89% following orchidectomy suggesting that persistence of tumor antigen is required to sustain CTAg-specific T-cell immunity. Notably, this decrease correlated with a decline in the global effector/memory T-cell pool following treatment. Spontaneous T-cell immunity against CTAg proteins therefore develops in many patients with testicular cancer and may play an important role in the excellent clinical outcome of patients with this tumor subtype.

Practitioner Review: Therapist variability, patient-reported therapeutic alliance, and clinical outcomes in adolescents undergoing mental health treatment - a systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses have only found small correlations (r = .10 to r = .19) between therapeutic alliance and clinical outcomes in samples of adolescents receiving psychological therapy. Although study-level variables have been found to moderate this, little is known about the impact of therapist variability. The present meta-analysis aimed to address this gap by using patient-therapist ratio as a moderator variable. METHODS: Contrary to previous reviews of adolescent alliance, individual effect sizes were extracted using a preregistered conceptual hierarchy. Controlling for treatment-level confounds, a random effects meta-analysis assessed the moderating effect of patient-therapist ratio on the alliance-outcome relationship in predefined single-predictor and multipredictor meta-regressions. RESULTS: The alliance-outcome relationship was found to be larger than previously thought (k = 28, N = 2,911, r = .29, 95% Confidence Interval 0.21, 0.37; p < .0001, I2  = 80%). When study samples exceeding the adolescent 12-19 age range were removed, the correlation rose (k = 15, N = 1,797, r = .34, 95% Confidence Interval 0.23, 0.45; p < .0001, I2  = 83%). In contrast to research with adults, patient-therapist ratio did not moderate this relationship in either single-predictor (p = .26) or multi-predictor (p = .22) models. CONCLUSIONS: The alliance-outcome relationship for adolescents was larger than previously thought, and comparable to estimates in adult samples. The failure of patient-therapist ratio to moderate its strength, however, challenges the hypothesis that variability in therapist characteristics is an important determinant of the alliance-outcome effect in this age group.

Psychological therapy for inpatients receiving acute mental health care: A systematic review and meta-analysis of controlled trials.

OBJECTIVES: The effectiveness of psychological therapies for those receiving acute adult mental health inpatient care remains unclear, partly because of the difficulty in conducting randomized controlled trials (RCTs) in this setting. The aim of this meta-analysis was to synthesize evidence from all controlled trials of psychological therapy carried out with this group, to estimate its effects on a number of important outcomes and examine whether the presence of randomization and rater blinding moderated these estimates. METHOD: A systematic review and meta-analysis of all controlled trials of psychological therapy delivered in acute inpatient settings was conducted, with a focus on psychotic symptoms, readmissions or emotional distress (anxiety and depression). Studies were identified through ASSIA, EMBASE, CINAHL, Cochrane, MEDLINE, and PsycINFO using a combination of the key terms 'inpatient', 'psychological therapy', and 'acute'. No restriction was placed on diagnosis. The moderating effect of the use of assessor-blind RCT methodology was examined via subgroup and sensitivity analyses. RESULTS: Overall, psychological therapy was associated with small-to-moderate improvements in psychotic symptoms at end of therapy but the effect was smaller and not significant at follow-up. Psychological therapy was also associated with reduced readmissions, depression, and anxiety. The use of single-blind randomized controlled trial methodology was associated with significantly reduced benefits on psychotic symptoms and was also associated with reduced benefits on readmission and depression; however, these reductions were not statistically significant. CONCLUSIONS: The provision of psychological therapy to acute psychiatric inpatients is associated with improvements; however, the use of single-blind RCT methodology was associated with reduced therapy-attributable improvements. Whether this is a consequence of increased internal validity or reduced external validity is unclear. Trials with both high internal and external validity are now required to establish what type, format, and intensity of brief psychological therapy is required to achieve sustained benefits. PRACTITIONER POINTS: Clinical implications: This review provides the first meta-analytical synthesis of brief psychological therapy delivered in acute psychiatric inpatient settings. This review suggests that brief psychological therapy may be associated with reduced emotional distress and readmissions. LIMITATIONS: The evidence in this review is of limited quality. The type, format, and intensity of brief psychological therapy required to achieve sustained benefits are yet to be established.

Systematic review and meta-analysis of factors that help or hinder treatment decision-making capacity in psychosis.

BackgroundThe evidence on factors that may influence treatment decisional capacity ('capacity') in psychosis has yet to be comprehensively synthesised, which limits the development of effective strategies to improve or support it.AimsTo determine the direction, magnitude and reliability of the relationship between capacity in psychosis and a range of clinical, demographic and treatment-related factors, thus providing a thorough synthesis of current knowledge.MethodWe conducted a systematic review, meta-analytical and narrative synthesis of factors that help or hinder treatment decision-making capacity in psychosis, assessing the direction, magnitude, significance and reliability of reported associations.ResultsWe identified 23 relevant studies (n = l823). Psychotic symptoms had small, moderate and strong associations with appreciation, understanding and reasoning respectively. Both verbal cognitive functioning and duration of education had small to moderate correlations with understanding and reasoning. Better capacity was also associated with better insight, better metacognitive ability, higher anxiety and lower perceived coercion. No linear relationship with depression was observed. Interventions linked to improved capacity over time were in-patient care, information simplification, shared decision-making and metacognitive training.ConclusionsAlthough much is known about the role of symptoms and other clinical variables, effective and acceptable psychological interventions to support capacity in this group are lacking.

Shared treatment decision-making and empowerment-related outcomes in psychosis: systematic review and meta-analysis.

BACKGROUND: In the UK almost 60% of people with a diagnosis of schizophrenia who use mental health services say they are not involved in decisions about their treatment. Guidelines and policy documents recommend that shared decision-making should be implemented, yet whether it leads to greater treatment-related empowerment for this group has not been systematically assessed. AIMS: To examine the effects of shared decision-making on indices of treatment-related empowerment of people with psychosis. METHOD: We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of shared decision-making concerning current or future treatment for psychosis (PROSPERO registration CRD42013006161). Primary outcomes were indices of treatment-related empowerment and objective coercion (compulsory treatment). Secondary outcomes were treatment decision-making ability and the quality of the therapeutic relationship. RESULTS: We identified 11 RCTs. Small beneficial effects of increased shared decision-making were found on indices of treatment-related empowerment (6 RCTs; g = 0.30, 95% CI 0.09-0.51), although the effect was smaller if trials with >25% missing data were excluded. There was a trend towards shared decision-making for future care leading to reduced use of compulsory treatment over 15-18 months (3 RCTs; RR = 0.59, 95% CI 0.35-1.02), with a number needed to treat of approximately 10 (95% CI 5-∞). No clear effect on treatment decision-making ability (3 RCTs) or the quality of the therapeutic relationship (8 RCTs) was found, but data were heterogeneous. CONCLUSIONS: For people with psychosis the implementation of shared treatment decision-making appears to have small beneficial effects on indices of treatment-related empowerment, but more direct evidence is required.

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 people with schizophrenia spectrum disorders not taking antipsychotic drugs: a single-blind randomised controlled trial.

BACKGROUND: Antipsychotic drugs are usually the first line of treatment for schizophrenia; however, many patients refuse or discontinue their pharmacological treatment. We aimed to establish whether cognitive therapy was effective in reducing psychiatric symptoms in people with schizophrenia spectrum disorders who had chosen not to take antipsychotic drugs. METHODS: We did a single-blind randomised controlled trial at two UK centres between Feb 15, 2010, and May 30, 2013. Participants aged 16-65 years with schizophrenia spectrum disorders, who had chosen not to take antipsychotic drugs for psychosis, were randomly assigned (1:1), by a computerised system with permuted block sizes of four or six, to receive cognitive therapy plus treatment as usual, or treatment as usual alone. Randomisation was stratified by study site. Outcome assessors were masked to group allocation. Our primary outcome was total score on the positive and negative syndrome scale (PANSS), which we assessed at baseline, and at months 3, 6, 9, 12, 15, and 18. Analysis was by intention to treat, with an ANCOVA model adjusted for site, age, sex, and baseline symptoms. This study is registered as an International Standard Randomised Controlled Trial, number 29607432. FINDINGS: 74 individuals were randomly assigned to receive either cognitive therapy plus treatment as usual (n=37), or treatment as usual alone (n=37). Mean PANSS total scores were consistently lower in the cognitive therapy group than in the treatment as usual group, with an estimated between-group effect size of -6.52 (95% CI -10.79 to -2.25; p=0.003). We recorded eight serious adverse events: two in patients in the cognitive therapy group (one attempted overdose and one patient presenting risk to others, both after therapy), and six in those in the treatment as usual group (two deaths, both of which were deemed unrelated to trial participation or mental health; three compulsory admissions to hospital for treatment under the mental health act; and one attempted overdose). INTERPRETATION: Cognitive therapy significantly reduced psychiatric symptoms and seems to be a safe and acceptable alternative for people with schizophrenia spectrum disorders who have chosen not to take antipsychotic drugs. Evidence-based treatments should be available to these individuals. A larger, definitive trial is needed. FUNDING: National Institute for Health Research.

Quetiapine immediate release v. placebo for schizophrenia: systematic review, meta-analysis and reappraisal.

BACKGROUND: Immediate-release (IR) quetiapine has been used to treat schizophrenia since 1997, although all the principal placebo-controlled trials have >50% missing outcome data. New studies with relatively lower rates of participant withdrawal have since been published. AIMS: To assess the efficacy and adverse effects of quetiapine IR for schizophrenia, with consideration of outcome quality and clinical meaningfulness of results, and to examine the potential impact of missing data on the main efficacy findings. METHOD: We conducted a systematic review and meta-analysis of randomised controlled trials comparing quetiapine IR and placebo (or subtherapeutic dose in relapse prevention trials) for the treatment of schizophrenia (PROSPERO registration CRD4201100165). Primary outcomes were change in overall symptoms and response rates. We also examined whether high rates of participant withdrawal (≥50%) attenuated effect sizes, and assessed the impact of making different assumptions about these people's outcomes. RESULTS: We identified 15 relevant trials (including 2 unpublished), providing the first 12-week data for this drug and the first data on self-reported quality of life. We found quetiapine IR to have a weighted mean difference (WMD) of 6.5 points (95% CI -8.9 to -4) on Positive and Negative Syndrome Scale (PANSS) total scores, which corresponds to a standardised mean difference (SMD) of -0.33 (95% CI -0.46 to -0.21). Longer trials reported larger mean differences favouring quetiapine IR, but the overall estimate was smaller if more conservative assumptions about the outcomes of people who left the trial early were made. Approximately 21 people needed to take quetiapine IR for 1 person to experience at least a 50% improvement in PANSS score. No difference in quality of life was observed (two RCTs), although small to moderate improvements in social functioning were found (three RCTs). Quetiapine IR caused sedation and increased rates of clinically significant weight gain, but no extrapyramidal effects were observed. CONCLUSIONS: Quetiapine IR has a small beneficial effect on overall psychotic symptoms over 2-12 weeks, but also leads to weight gain and sedation.

Confirming the structure of negative beliefs about psychosis and bipolar disorder: A confirmatory factor analysis study of the Personal Beliefs about Experience Questionnaire and Personal Beliefs about Illness Questionnaire.

OBJECTIVES: Negative beliefs about psychosis and other mental health difficulties may contribute to depression and distress in individuals with these experiences. The Personal Beliefs about Experience Questionnaire (PBEQ) and Personal Beliefs about Illness Questionnaire (PBIllQ) are two widely used measures of these beliefs. It is currently uncertain how the items on these measures map onto different underlying factors. This study therefore aimed to test the factor structure of these two measures. METHODS: Confirmatory factor analysis (CFA) was used to test three alternative, pre-specified, factor structures for the PBIllQ and PBEQ in a sample of individuals diagnosed with bipolar disorder (n = 202) and a sample of individuals with experien-ces of psychosis (n = 362). Associations with depressive symptoms were also examined. RESULT: A three-factor structure was supported for both measures, which included Negative Expectations/Appraisals (NEA), Internal Shame/Defectiveness (ISD) and External Shame (ES) factors. The NEA and ISD subscales also had consistent independent associations with depressive symptoms. CONCLUSIONS: The results suggest that the PBIllQ and PBEQ may capture three distinct sets of negative beliefs in individuals with psychosis or bipolar disorder and that these beliefs may have important consequences for subsequent difficulties in these populations such as depression. Both measures may be helpful in supporting assessment and formulation in clinical practice and in evaluating belief change in intervention trials. However, when used in these settings, the three subscales identified in this study may be the most valid way of calculating scores on these measures. PRACTITIONER POINTS: Negative personal beliefs about the causes, meaning and consequences of psychosis and bipolar disorder are associated with greater distress and depression. Two related measures, the PBIllQ and PBEQ, have been developed to assess these beliefs. Our analyses suggest that scores on these questionnaires are best broken down into three subscales which capture perceptions of internal shame or defectiveness, general negative appraisals and perceptions of external shame. These subscales may capture key underlying sets of negative beliefs within individuals with psychosis or bipolar disorder, which in turn impact upon well-being, such as being associated with greater depression. These subscales can be used to aid assessment and formulation within clinical practice but may also provide a valuable means of assessing changes in negative beliefs following interventions.

Metacognitive therapy in treatment-resistant psychosis: a multiple-baseline study.

BACKGROUND: More effective psychological treatments for psychosis are required. Case series data and pilot trials suggest metacognitive therapy (MCT) is a promising treatment for anxiety and depression. Other research has found negative metacognitive beliefs and thought-control strategies may be involved in the development and maintenance of hallucinations and delusions. The potential of MCT in treating psychosis has yet to be investigated. AIMS: Our aim was to find out whether a short number of MCT sessions would be associated with clinically significant and sustained improvements in delusions, hallucinations, anxiety, depression and subjective recovery in patients with treatment-resistant long-standing psychosis. METHOD: Three consecutively referred patients, each with a diagnosis of paranoid schizophrenia and continuing symptoms, completed a series of multiple baseline assessments. Each then received between 11 and 13 sessions of MCT and completed regular assessments of progress, during therapy, post-therapy and at 3-month follow-up. RESULTS: Two out of 3 participants achieved clinically significant reductions across a range of symptom-based outcomes at end-of-therapy. Improvement was sustained at 3-month follow-up for one participant. CONCLUSIONS: Our study demonstrates the feasibility of using MCT with people with medication-resistant psychosis. MCT was acceptable to the participants and associated with meaningful change. Some modifications may be required for this population, after which a controlled trial may be warranted.

Accelerating the development of a psychological intervention to restore treatment decision-making capacity in patients with schizophrenia-spectrum disorder: a study protocol for a multi-site, assessor-blinded, pilot Umbrella trial (the DEC:IDES trial).

BACKGROUND: A high proportion of patients diagnosed with schizophrenia-spectrum disorders will at some point in their lives be assessed as not having the capacity to make their own decisions about pharmacological treatment or inpatient care ('capacity'). Few will be helped to regain it before these interventions proceed. This is partly because effective and safe methods to do so are lacking. Our aim is to accelerate their development by testing, for the first time in mental healthcare, the feasibility, acceptability and safety of running an 'Umbrella' trial. This involves running, concurrently and under one multi-site infrastructure, multiple assessor-blind randomised controlled trials, each of which is designed to examine the effect on capacity of improving a single psychological mechanism ('mechanism'). Our primary objectives are to demonstrate feasibility of (i) recruitment and (ii) data retention on the MacArthur Competence Assessment Tool-Treatment (MacCAT-T; planned primary outcome for a future trial) at end-of-treatment. We selected three mechanisms to test: 'self-stigma', low self-esteem and the 'jumping to conclusions' bias. Each is highly prevalent in psychosis, responsive to psychological intervention, and hypothesised to contribute to impaired capacity. METHODS: Sixty participants with schizophrenia-spectrum diagnoses, impaired capacity and one or more mechanism(s) will be recruited from outpatient and inpatient mental health services in three UK sites (Lothian, Scotland; Lancashire and Pennine; North West England). Those lacking capacity to consent to research could take part if the key criteria were met, including either proxy consent (Scotland) or favourable Consultee advice (England). They will be allocated to one of three randomised controlled trials, depending on which mechanism(s) they have. They will then be randomised to receive, over an 8-week period and in addition to treatment as usual (TAU), 6 sessions of either a psychological intervention which targets the mechanism, or 6 sessions of assessment of the causes of their incapacity (control condition). Participants are assessed at 0 (baseline), 8 (end-of-treatment) and 24 (follow-up) weeks post-randomisation using measures of capacity (MacCAT-T), mechanism, adverse events, psychotic symptoms, subjective recovery, quality of life, service use, anxiety, core schemata and depression. Two nested qualitative studies will be conducted; one to understand participant and clinician experiences and one to investigate the validity of MacCAT-T appreciation ratings. DISCUSSION: This will be the first Umbrella trial in mental healthcare. It will produce the first 3 single-blind randomised controlled trials of psychological interventions to support treatment decision-making in schizophrenia-spectrum disorder. Demonstrating feasibility will have significant implications not only for those seeking to support capacity in psychosis, but also for those who wish to accelerate the development of psychological interventions for other conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT04309435 . Pre-registered on 16 March 2020.

Antipsychotics: is it time to introduce patient choice?

Evidence regarding overestimation of the efficacy of antipsychotics and underestimation of their toxicity, as well as emerging data regarding alternative treatment options, suggests it may be time to introduce patient choice and reconsider whether everyone who meets the criteria for a schizophrenia spectrum diagnosis requires antipsychotics in order to recover.

Brief cognitive behavioural therapy for hallucinations: can it help people who decide not to take antipsychotic medication? A case report.

BACKGROUND: Cognitive behavioural therapy (CBT) can be helpful for many people who experience psychosis; however most research trials have been conducted with people also taking antipsychotic medication. There is little evidence to know whether CBT can help people who choose not to take this medication, despite this being a very frequent event. Developing effective alternatives to antipsychotics would offer service users real choice. AIMS: To report a case study illustrating how brief CBT may be of value to a young person experiencing psychosis and not wishing to take antipsychotic medication. METHOD: We describe the progress of brief CBT for a young man reporting auditory and visual hallucinations in the form of a controlling and dominating invisible companion. We describe the formulation process and discuss the impact of key interventions such as normalising and detached mindfulness. RESULTS: Seven sessions of CBT resulted in complete disappearance of the invisible companion. The reduction in frequency and duration followed reduction in conviction in key appraisals concerning uncontrollability and unacceptability. CONCLUSIONS: This case adds to the existing evidence base by suggesting that even short-term CBT might lead to valued outcomes for service users experiencing psychosis but not wishing to take antipsychotic medication.

A network meta-analysis of psychological interventions for schizophrenia and psychosis: Impact on symptoms.

BACKGROUND: Evidence for the effectiveness of psychological interventions for schizophrenia/psychosis is growing, however there is no consensus on the psychological intervention most likely to reduce symptoms. METHODS: A network meta-analysis was conducted to identify all randomised controlled trials (RCTs) of psychological interventions for adults with schizophrenia/psychosis. A systematic review of the literature using MEDLINE, PsycINFO, EMBASE and CENTRAL led to an analysis of 90 RCTs with 8440 randomised participants across 24 psychological intervention, and control groups. Psychological interventions were categorised and rated for treatment fidelity and risk of bias. Data for total symptoms were extracted and network meta-analysis, using a frequentist approach, was undertaken using Stata SE v15 to compare the direct and indirect evidence for the effectiveness of each psychological intervention. FINDINGS: Psychological interventions were more likely to reduce symptoms than control groups, and one intervention, mindfulness-based psychoeducation, was consistently ranked as most likely to reduce total symptoms. Subgroup analyses identified differential effectiveness in different settings and for different subgroups. INTERPRETATION: Mindfulness-based psychoeducation was consistently ranked as most likely to reduce symptoms; however all studies were based in China. More RCTs in a variety of cultural contexts would help to elucidate whether these findings generalise internationally. A number of psychological interventions could potentially be more effective than interventions recommended by NICE guidelines, such as CBT and family therapy, and additional RCTs and meta-analyses are needed to generate more conclusive evidence in this regard.

The 111 Study: A Single-arm, Phase 3 Trial Evaluating One Cycle of Bleomycin, Etoposide, and Cisplatin as Adjuvant Chemotherapy in High-risk, Stage 1 Nonseminomatous or Combined Germ Cell Tumours of the Testis.

BACKGROUND: Standard management in the UK for high-risk stage 1 nonseminoma germ cell tumours of the testis (NSGCTT) is two cycles of adjuvant bleomycin, etoposide (360 mg/m2), and cisplatin (BE360P) chemotherapy, or surveillance. OBJECTIVE: To test whether one cycle of BE500P achieves similar recurrence rates to two cycles of BE360P. DESIGN, SETTING, AND PARTICIPANTS: A total of 246 patients with vascular invasion-positive stage 1 NSGCTT or combined seminoma + NSGCTT were centrally registered in a single-arm prospective study. INTERVENTION: One cycle comprising bleomycin 30000 IU on days 1, 8, and 15, etoposide 165 mg/m2 on days 1-3, and cisplatin 50 mg/m2 on days 1-2, plus antibacterial and granulocyte colony stimulating factor prophylaxis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was 2-yr malignant recurrence (MR); the aim was to exclude a rate of ≥5%. Participants had regular imaging and tumour marker (TM) assessment for 5 yr. RESULTS AND LIMITATIONS: The median follow-up was 49 mo (interquartile range 37-60). Ten patients with rising TMs at baseline were excluded. Four patients had MR at 6, 7, 13, and 27 mo; all received second-line chemotherapy and surgery and three remained recurrence-free at 5 yr. The 2-yr MR rate was 1.3% (95% confidence interval 0.3-3.7%). Three patients developed nonmalignant recurrences with localised teratoma differentiated, rendered disease-free after surgery. Grade 3-4 febrile neutropenia occurred in 6.8% of participants. CONCLUSIONS: BE500P is safe and the 2-yr MR rate is consistent with that seen following two BE360P cycles. The 111 study is the largest prospective trial investigating one cycle of adjuvant BE500P in high-risk stage 1 NSGCTT. Adoption of one cycle of BE500P as standard would reduce overall exposure to chemotherapy in this young population. PATIENT SUMMARY: Removing the testicle fails to cure many patients with high-risk primary testicular cancer since undetectable cancers are often present elsewhere. A standard additional treatment in Europe is two cycles of chemotherapy to eradicate these. This trial shows one cycle has few adverse effects and comparable outcomes to those seen with two cycles.