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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. 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. 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). 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. National Institute for Health Research.

Background People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. Methods A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). Discussion There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options. Trial registration ISRCTN33079589. Registered on June 20, 2022.

Background Adolescent-onset psychosis is associated with more severe symptoms and poorer outcomes than adult-onset psychosis. The National Institute for Clinical Excellence (NICE) recommend that adolescents with first episode psychosis (FEP) should be offered a combination of antipsychotic medication (APs), cognitive behavioural therapy (CBT) and family intervention (FI). The evidence for APs in treating psychosis is limited in adolescents compared to adults. Nevertheless, it indicates that APs can reduce overall symptoms in adolescents but may cause more severe side effects, including cardiovascular and metabolic effects, than in adults. CBT and FI can improve outcomes in adults, but there are no studies of psychological interventions (PI) in patients under 18 years old. Given this limited evidence base, NICE made a specific research recommendation for determining the clinical and cost effectiveness of APs versus PI versus both treatments for adolescent FEP. Methods/design The current study aimed to establish the feasibility and acceptability of conducting such a trial by recruiting 14–18-year-olds with a first episode of psychosis into a feasibility prospective randomised open blinded evaluation (PROBE) design, three-arm, randomised controlled trial of APs alone versus PI alone versus a combination of both treatments. We aimed to recruit 90 participants from Early Intervention and Child and Adolescent Mental Health Teams in seven UK sites. APs were prescribed by participants’ usual psychiatrists. PI comprised standardised cognitive behavioural therapy and family intervention sessions. Discussion This is the first study to compare APs to PI in an adolescent population with FEP. Recruitment finished on 31 October 2018. The study faced difficulties with recruitment across most sites due to factors including clinician and service-user treatment preferences. Trial registration Current controlled trial with ISRCTN, ISRCTN80567433 . Registered on 27 February 2017.

Abstract Background There is little head-to-head data comparing cognitive behavior therapy for psychosis (CBTp) and antipsychotic medication (APs). However, several recent trials have been conducted in first episode psychosis. We report a pre-specified individual participant data (IPD) pooled analysis utilizing data from two randomized controlled trials (RCTs) with similar designs to examine relative effectiveness. Study Design The outcomes were psychiatric symptoms (Positive and Negative Syndrome Scale: PANSS) and recovery (Questionnaire about the Process of Recovery: QPR) at 6 months. One-stage and two-stage IPD meta-analyses were performed based on the intention-to-treat principle. Serious adverse events are also summarized. Study Results Two RCTs were included in the pooled IPD analysis which provided 136 participants. For PANSS total at 6 months, the one-stage meta-analysis found no evidence of a difference between CBTp alone and APs alone (mean difference 2.58, 95% CI, -2.83 to 7.98; P-value 0.35) and CBTp alone compared with APs plus CBTp (MD -5.91; 95% CI, -12.14 to 0.31; P-value 0.063). For APs alone compared to CBTp plus APs there was evidence of a difference (MD -8.49; 95% CI, -14.65 to -2.33; P-value 0.007) favoring the combined treatment. For user-defined recovery (QPR), there was a difference favoring CBTp plus APs in comparison to both CBTp alone (P-value 0.029) and APs alone (P-value 0.026), but no difference between the monotherapies (P-value 0.91). The most common serious adverse events were psychiatric hospital admissions. Conclusions Cognitive behavior therapy for psychosis and APs did not differ in their effects on symptoms or recovery, but there were suggestions that the combined treatment may be superior. A definitive RCT is warranted.

This study aimed to describe the causal beliefs of individuals experiencing psychosis, specifically exploring how they are developed and maintained. Individuals with experience of psychosis were recruited from mental health services for in-depth interviews. A thematic analysis was used to analyse transcripts and key themes were identified. Fifteen interviews were conducted. Individuals were engaged in the process of exploring explanations for their experiences and reported sophisticated models of causation. Participants described a change in their beliefs, with the cause of their experiences not immediately clear. Individuals generated their models via external (family, professionals) and internal (evaluative, positive affect) processes and reported differing levels of conviction in relation to their beliefs. Clinicians should take the opportunity to explore the causal beliefs of their service-users, as they are able to provide intelligent and thoughtful explanatory models. In particular, clinicians should be aware of the emotional impact of different aetiological models and their personal role in the development of a client’s beliefs.

Stigma of mental health conditions hinders recovery and well-being. The Honest, Open, Proud (HOP) program shows promise in reducing stigma but there is uncertainty about the feasibility of a randomized trial to evaluate a peer-delivered, individual adaptation of HOP for psychosis (Let's Talk). A multi-site, Prospective Randomized Open Blinded Evaluation (PROBE) design, feasibility randomised controlled trial (RCT) comparing the peer-delivered intervention (Let's Talk) to treatment as usual (TAU). Follow-up was 2.5 and 6 months. Randomization was via a web-based system, with permuted blocks of random size. Up to 10 sessions of the intervention over 10 weeks were offered. The primary outcome was feasibility data (recruitment, retention, intervention attendance). Primary outcomes were analyzed by intention to treat. Safety outcomes were reported by as treated status. The study was prospectively registered: https://doi.org/10.1186/ISRCTN17197043. 149 patients were referred to the study and 70 were recruited. 35 were randomly assigned to intervention + TAU and 35 to TAU. Recruitment was 93% of the target sample size. Retention rate was high (81% at 2.5 months primary endpoint), and intervention attendance rate was high (83%). 21% of 33 patients in Let's talk + TAU had an adverse event and 16% of 37 patients in TAU. One serious adverse event (pre-randomization) was partially related and expected. This is the first trial to show that it is feasible and safe to conduct a RCT of HOP adapted for people with psychosis and individual delivery. An adequately powered trial is required to provide robust evidence.

Background Hearing voices (“auditory hallucinations”) is associated with numerous negative outcomes, including hospitalisation, suicidality, and impaired functioning. Currently, the main treatment approaches are antipsychotic medication and cognitive behavioural therapy (CBT), yet both have variable effectiveness and are often unavailable to those without a schizophrenia diagnosis. Furthermore, CBT does not consistently address the role of trauma in voice onset and maintenance. In response to these unmet needs, a feasibility/acceptability trial of a new intervention, Talking With Voices (TWV), was conducted. TWV involves a therapist speaking to the voice(s) while the client repeats its response verbatim, with the aim of promoting recovery and reducing voice-related distress. This prior pilot study ( N  = 50) found excellent feasibility/acceptability data amongst participants with schizophrenia, and signals of positive change in measures of personal recovery and voice relating. The next step is to evaluate treatment mechanisms and clinical efficacy of TWV in a transdiagnostic population. Methods We aim to establish TWV’s clinical efficacy in a multisite RCT for adults with serious mental health problems (SMHP) who hear persistent, distressing voices, and to assess whether improved measures of personal recovery and negative voice impact are mediated via key psychological mechanisms (improved relating to, and beliefs about, voices; and reductions in dissociation and negative self-beliefs). We aim to recruit 296 participants from psychiatric services across 4 UK sites (Manchester, London, Newcastle, and Oxford) who will be randomised to either treatment (TWV + treatment as usual [TAU]) or control (TAU only). The primary outcome is total score on the Questionnaire About the Process of Recovery. Secondary outcomes include overall voice severity and other relevant dimensions of voices and trauma sequalae, with mediational and outcome variables collected at baseline, 8 months (post-treatment), and 14 months. Discussion The study will investigate the clinical efficacy of a novel intervention deliverable within healthcare services, including hypothesised mechanisms of change to identify key psychological targets for ameliorating distressing voices in a transdiagnostic population. Potential benefits include improving the effectiveness and accessibility of evidence-based psychosocial interventions for SMHP. Trial registration ISRCTN, ISRCTN15897915. Registered 13 July 2023.

People with serious mental health problems (SMHP) are more likely to be admitted to psychiatric hospital following contact with crisis services. Admissions can have significant personal costs, be traumatic and are the most expensive form of mental health care. There is an urgent need for treatments to reduce suicidal thoughts and behaviours and reduce avoidable psychiatric admissions. A multi-stage, multi-arm (MAMS) randomised controlled trial (RCT) with four arms conducted over two stages to determine the clinical and cost effectiveness of three psychosocial treatments, compared to treatment as usual (TAU), for people with SMHP who have had recent suicidal crisis. Primary outcome is any psychiatric hospital admissions over a 6-month period. We will assess the impact on suicidal thoughts and behaviour, hope, recovery, anxiety and depression. The remote treatments delivered over 3 months are structured peer support (PREVAIL); a safety planning approach (SAFETEL) delivered by assistant psychologists; and a CBT-based suicide prevention app accessed via a smartphone (BrighterSide). Recruitment is at five UK sites. Stage 1 includes an internal pilot with a priori progression criteria. In stage 1, the randomisation ratio was 1:1:1:2 in favour of TAU. This has been amended to 2:2:3 in favour of TAU following an unplanned change to remove the BrighterSide arm following the release of efficacy data from an independent RCT. Randomisation is via an independent remote web-based randomisation system using randomly permuted blocks, stratified by site. An interim analysis will be performed using data from the first 385 participants from PREVAIL, SAFETEL and TAU with outcome data at 6 months. If one arm is dropped for lack of benefit in stage 2, the allocation ratio of future participants will be 1:1. The expected total sample size is 1064 participants (1118 inclusive of BrighterSide participants). There is a need for evidence-based interventions to reduce psychiatric admissions, via reduction of suicidality. Our focus on remote delivery of established brief psychosocial interventions, utilisation of different modalities of delivery that can provide sustainable and scalable solutions, which are also suitable for a pandemic or national crisis context, will significantly advance treatment options.

Internalised stigma in young people meeting criteria for at-risk mental states (ARMS) has been highlighted as an important issue, and it has been suggested that provision of cognitive therapy may increase such stigma. To investigate the effects of cognitive therapy on internalised stigma using a secondary analysis of data from the EDIE-2 trial. Participants meeting criteria for ARMS were recruited as part of a multisite randomised controlled trial of cognitive therapy for prevention and amelioration of psychosis. Participants were assessed at baseline and at 6, 12, 18 and 24 months using measures of psychotic experiences, symptoms and internalised stigma. Negative appraisals of experiences were significantly reduced in the group assigned to cognitive therapy (estimated difference at 12 months was -1.36 (95% CI -2.69 to -0.02), P = 0.047). There was no difference in social acceptability of experiences (estimated difference at 12 months was 0.46, 95% CI -0.05 to 0.98, P = 0.079). These findings suggest that, rather than increasing internalised stigma, cognitive therapy decreases negative appraisals of unusual experiences in young people at risk of psychosis; as such, it is a non-stigmatising intervention for this population.

The claim that missing data is over 50% at follow-up points is based on use of the randomised number as denominator, rather than the number who could have potentially provided outcome assessments given the planned variable length of follow-up (adopted to provide value for money to the funder, allowing maximal recruitment, and the most complete data we could gather in the lifetime of the trial).