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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., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Research meta-analyses have found that cognitive-behavioral therapy (CBT) is beneficial for persistent symptoms of schizophrenia. This review describes and updates the evidence base for this statement. A review of the existing literature (Medline, PsychInfo, and Embase) was carried out according to the guidelines for systematic reviews. Based on the findings of this review, the updated conclusion is that CBT has emerged as an effective adjuvant to antipsychotic medication in the treatment of persistent symptoms of schizophrenia. Studies of the use of CBT in the prodromal phase of psychosis and in combination with family therapy are currently underway.

When clinicians adopt the standard 16–26 session maximum suggested by CBTp efficacy research, clients with long-term medication resistant psychosis may receive an inadequate dose of therapy. Building engagement and trust can take significantly longer for clients who have been given a stigmatizing medical explanation for their difficulties. We present a case study of successful long-term CBTp consisting of 200 sessions over a 6-year period. Supervision aided the recovery process over the last 2 years of therapy. A client with a 30-year history of medication resistant persecutory delusions, voices, stigma and prominent negative symptoms gradually formed a working alliance with the therapist. A CBT formulation emphasizing activating the adaptive mode led to later targeted work to reduce distress and social avoidance and address underlying trauma. Social recovery was achieved with increased independence and enhanced creativity. A commentary is provided by a senior clinician from a psychodynamic perspective. Clients with long-term medication resistant psychosis often need an increased number of CBT sessions but can still recover. Ongoing supportive supervision prevents early discharge and a failure to achieve a recovery trajectory. We should not accept that medication resistant clients are CBT resistant following a brief course of therapy. [ABSTRACT FROM AUTHOR]

Between 5% and 10% of people with psychosis will die by suicide, a rate which is 20–75 times higher than the general population. This risk is even greater in those not taking antipsychotic medication. We examined whether negative appraisals of psychotic experiences and negative metacognitive beliefs about losing mental control mediated a relationship between psychotic symptoms and suicidal ideation in this group. Participants were diagnosed with schizophrenia spectrum disorders, antipsychotic-free for 6 months at baseline, and were participating in an 18-month randomized controlled trial of cognitive therapy vs treatment as usual. We conducted a series of mediation analyses with bootstrapping on baseline (N = 68), follow-up data (9–18 mo; n = 49), and longitudinal data (n = 47). Concurrent general symptoms were directly associated with suicidal ideation at baseline, and concurrent negative symptoms were directly associated with suicidal ideation at 9–18 months. Concurrent positive, negative, general, and overall symptoms were each indirectly associated with suicidal ideation via negative appraisals and/or negative metacognitive beliefs, at baseline and 9–18 months, except for negative symptoms at baseline. Controlling for baseline suicidal ideation and treatment allocation, baseline general symptoms were indirectly associated with later suicidal ideation, via baseline negative appraisals and negative metacognitive beliefs. Baseline negative metacognitive beliefs also had a direct association with later suicidal ideation. These findings suggest the clinical assessment of suicidal ideation in psychosis may be enhanced by considering metacognitive beliefs about the probability and consequences of losing mental control. [ABSTRACT FROM AUTHOR]

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 29th November 2012. [ABSTRACT FROM AUTHOR]

This study explores relationships between internalised stereotypes (IS) and emotional dysfunction in people with psychosis who are not taking antipsychotic medication. Cross-sectional and longitudinal data for 66 participants were tested for relationships between IS, emotional dysfunction and insight at baseline and three months. IS and insight at baseline were compared between those with psychological and other causal models of psychosis. High levels of IS were associated with depression and social anxiety at baseline. Internalised stereotypes contributed to the variance in depression over time. Participants who reported a psychological causal model for their psychotic experiences had significantly lower levels of stigma. Findings support a stigma model of emotional dysfunction in people with psychosis replicating previous findings in an antipsychotic free group. Research is required to demonstrate effective interventions for IS in those with psychosis. [ABSTRACT FROM AUTHOR]

Little is known about the types of coping strategies activated by clients suffering from distressing hallucinatory voices and even less about models of coping. This study categorises those coping approaches as distraction, focusing or metacognitive and reports on their frequency in a community sample of voice hearers using thematic analysis. A non-engagement style was found to be predominant and this was linked to coping by distraction and the use of safety behaviours. This study suggests that coping strategies naturally utilised by voice hearers tend to be of limited benefit and may perpetuate the voice hearing experience. It is suggested that hearing voices groups, mental health and CBT training programmes need to stress the importance of voice hearers moving towards focusing and metacognitive styles of coping. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Cognitive behaviour therapy (CBT) has been shown to be effective in an open trial for people with psychotic disorders who have not been taking antipsychotic medication. There is little known about predictors of outcome in CBT for psychosis and even less about hypothesised mechanisms of change. Method: 20 participants with schizophrenia spectrum disorders received CBT in an exploratory trial. Our primary outcome was psychiatric symptoms measured using the PANSS. Secondary outcomes were dimensions of hallucinations and delusions, self-rated recovery and social functioning, and hypothesised mechanisms of change included appraisals of psychotic experiences, dysfunctional attitudes and cognitive insight. We also measured patient characteristics that may be associated with outcome. Results: T-tests revealed that several of the hypothesised mechanisms did significantly change over the treatment and follow-up periods. Correlational analyses showed that reductions in negative appraisals of psychotic experiences were related to improvements on outcome measures and that shorter duration of psychosis and younger age were associated with greater changes in symptoms. Conclusions: CBT based on a specific cognitive model appears to change the hypothesised cognitive mechanisms, and these changes are associated with good outcomes. CBT may be more effective for those who are younger with shorter histories of psychosis. [Copyright &y& Elsevier]

Objective: A growing body of evidence supports the use of cognitive behavior therapy for the treatment of schizophrenia. A course of cognitive behavior therapy, added to the antipsychotic regimen, is now considered to be an appropriate standard of care in the United Kingdom. The objective of this article is to offer a broad perspective on the subject of cognitive behavior therapy for schizophrenia for the American reader. Method: The authors summarize current practice and data supporting the use of cognitive behavior therapy for schizophrenia, Results: Five aspects of cognitive behavior therapy for schizophrenia are addressed: 1) evidence from randomized clinical trials, 2) currently accepted core techniques, 3) similarities to and differences from other psychosocial interventions for schizophrenia, 4) differences between the United States and United Kingdom in implementation, and 5) current directions of research. Conclusions: The strength of the evidence supporting cognitive behavior therapy for schizophrenia suggests that this technique should have more attention and support in the United States. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The aim of the study was to investigate whether a scale based on 10 selected items from the Comprehensive Psychopathological Rating Scale (CPRS) correlated with the widely used Schedule for the Assessment of Negative Symptoms (SANS) in measuring symptom severity and change in a group of patients suffering from chronic schizophrenia. METHOD: Ninety patients with a diagnosis of schizophrenia were recruited from five British clinical services. The patients were all resistant to conventional antipsychotic medication. The patients were divided into two groups that received Befriending (BF) or Cognitive-behavioural therapy (CBT). The patients were scored on the CPRS and the SANS three times, before and after the therapy and again at 9 months follow-up. Tests for normality or skewness confirmed a normal distribution and therefore Pearson's correlation coefficient was used. RESULTS: The initial assessment showed a correlation of 0.56, the second had a correlation of 0.57, whilst the last follow-up correlation had increased to 0.87. CONCLUSION: The correlations at all three assessment points were acceptable. The new rating scale is (a) shorter than the SANS; (b) a valid measure of negative symptom severity; (c) sensitive to change; and (d) allows negative symptom scores to be abstracted from CPRS ratings. [ABSTRACT FROM AUTHOR]

This study investigated the effect of "dose" and the components of Cognitive Behavioral Therapy (CBT) on treatment effects. It is a secondary analysis of the ACTION (Assessment of Cognitive Therapy Instead of Neuroleptics) trial which investigated CBT for people with schizophrenia spectrum disorders that chose not to take antipsychotic medication. Using instrumental variable methods, we found a "dose-response" such that each CBT session attended, reduced the primary outcome measure (the PANSS total score) by approximately 0.6 points (95% CI -1.20 to -0.06, p = 0.031). This suggests that length of therapy is important for those that receive CBT in the absence of antipsychotic medication. Secondly, using principal stratification we examined the process variables that modified treatment effects. Findings revealed that those who received a longitudinal formulation in the first 4 sessions of CBT had poorer treatment effects than those who did not, however this finding was not statistically significant (95% CI -37.244, 6.677, p = 0.173). However, it is important to note that these findings were evident in an exploratory analysis with a small sample. Future larger scale studies are needed to help understand components of effective treatment. [ABSTRACT FROM AUTHOR]