Protocol for individual participant data meta-analysis of randomised controlled trials of patients with psychosis to investigate treatment effect modifiers for CBT versus treatment as usual or other psychosocial interventions.

INTRODUCTION: Aggregate data meta-analyses have shown heterogeneous treatment effects for cognitive-behavioural therapy (CBT) for patients with schizophrenia spectrum diagnoses. This heterogeneity could stem from specific intervention or patient characteristics that could influence the clinical effectiveness of CBT, termed treatment effect modifiers. This individual participant data meta-analysis will investigate a range of potential treatment effect modifiers of the efficacy of CBT. METHODS AND ANALYSIS: We will perform a systematic review and meta-analysis of studies investigating CBT versus treatment as usual, or CBT versus other psychosocial interventions, for patients with schizophrenia spectrum diagnoses. The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE and the online clinical trials registers of the US government, European Union, WHO and Current Controlled Trials will be searched. Two researchers will screen titles and abstracts identified by the search. Individual participant data will be requested for any eligible study, for the primary outcome (overall psychotic symptoms), secondary outcomes and treatment effect modifiers. Data will be checked and recoded according to an established statistical analysis plan. One-stage and two-stage random effects meta-analyses investigating potential treatment effect modifiers will be conducted. A list of potential treatment effect modifiers for CBT will be produced, motivating future research into particular modifiers. ETHICS AND DISSEMINATION: This study does not require ethical approval as it is based on data from existing studies, although best ethical practice for secondary analysis of clinical data will be followed. The findings will be submitted for publication in peer-reviewed journals, and promoted to relevant stakeholders. PROSPERO REGISTRATION NUMBER: CRD42017060068.

Long-term outcomes of psychological interventions on children and young people's mental health: A systematic review and meta-analysis.

BACKGROUND: Over 600 RCTs have demonstrated the effectiveness of psychosocial interventions for children and young people's mental health, but little is known about the long-term outcomes. This systematic review sought to establish whether the effects of selective and indicated interventions were sustained at 12 months. METHOD: We conducted a systematic review and meta-analysis focusing on studies reporting medium term outcomes (12 months after end of intervention). FINDINGS: We identified 138 trials with 12-month follow-up data, yielding 165 comparisons, 99 of which also reported outcomes at end of intervention, yielding 117 comparisons. We found evidence of effect relative to control at end of intervention (K = 115, g = 0.39; 95% CI: 0.30-0.47 I2 = 84.19%, N = 13,982) which was maintained at 12 months (K = 165, g = 0.31, CI: 0.25-0.37, I2 = 77.35%, N = 25,652) across a range of diagnostic groups. We explored the impact of potential moderators on outcome, including modality, format and intensity of intervention, selective or indicated intervention, site of delivery, professional/para-professional and fidelity of delivery. We assessed both risk of study bias and publication bias. CONCLUSIONS: Psychosocial interventions provided in a range of settings by professionals and paraprofessionals can deliver lasting benefits. High levels of heterogeneity, moderate to high risk of bias for most studies and evidence of publication bias require caution in interpreting the results. Lack of studies in diagnostic groups such as ADHD and self-harm limit the conclusions that can be drawn. Programmes that increase such interventions' availability are justified by the benefits to children and young people and the decreased likelihood of disorder in adulthood.

Individual Placement and Support (IPS) in England.

OBJECTIVE: The purpose of this report is to provide an overview of the current provision and policy focus on Individual Placement and Support (IPS) in England. METHOD: This report reviews current and future national developments shaping the future direction of IPS in England. RESULTS: Recent government policy announcements have led to an increased interest and focus on IPS nationally throughout England, leading to an expected growth in the numbers of people with a serious mental illness able to access employment support. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: England has the potential to become an exemplar of the supported employment approach and helping people with mental health problems get back to work, allowing individuals the opportunity to recover and access the benefits that employment can bring. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Self-management interventions for people with severe mental illness: systematic review and meta-analysis.

BACKGROUND: Self-management is intended to empower individuals in their recovery by providing the skills and confidence they need to take active steps in recognising and managing their own health problems. Evidence supports such interventions in a range of long-term physical health conditions, but a recent systematic synthesis is not available for people with severe mental health problems.AimsTo evaluate the effectiveness of self-management interventions for adults with severe mental illness (SMI). METHOD: A systematic review of randomised controlled trials was conducted. A meta-analysis of symptomatic, relapse, recovery, functioning and quality of life outcomes was conducted, using RevMan. RESULTS: A total of 37 trials were included with 5790 participants. From the meta-analysis, self-management interventions conferred benefits in terms of reducing symptoms and length of admission, and improving functioning and quality of life both at the end of treatment and at follow-up. Overall the effect size was small to medium. The evidence for self-management interventions on readmissions was mixed. However, self-management did have a significant effect compared with control on subjective measures of recovery such as hope and empowerment at follow-up, and self-rated recovery and self-efficacy at both time points. CONCLUSION: There is evidence that the provision of self-management interventions alongside standard care improves outcomes for people with SMI. Self-management interventions should form part of the standard package of care provided to people with SMI and should be prioritised in guidelines: research on best methods of implementing such interventions in routine practice is needed.Declaration of interestsNone.

Effectiveness of CBT for children and adolescents with depression: A systematic review and meta-regression analysis.

BACKGROUND: Cognitive-behavioral therapy (CBT) is first choice of treatment for depressive symptoms and disorders in adolescents, however improvements are necessary because overall efficacy is low. Insights on CBT components and contextual and structural characteristics might increase the efficacy. The aim of our approach is to evaluate the efficacy of CBT for youth with depression and investigate the influence of specific components, contextual and structural factors that could improve effects. METHODS: A systematic review of randomized controlled trials was conducted, searches were undertaken in CINAHL, CENTRAL, EMBASE, MEDLINE/PubMed and PsycINFO. Outcomes were meta-analyzed and confidence in results was assessed using the GRADE-method. Meta-regression was used to pinpoint components or other factors that were associated with an in- or decrease of effects of CBT. RESULTS: We included 31 trials with 4335 participants. Moderate-quality evidence was found for CBT reducing depressive symptoms at the end of treatment and at follow-up, and CBT as indicated prevention resulted in 63% less risk of being depressed at follow-up. CBT containing a combination of behavioral activation and challenging thoughts component (as part of cognitive restructuring) or the involvement of caregiver(s) in intervention were associated with better outcomes for youth on the long term. CONCLUSIONS: There is evidence that CBT is effective for youth with a (subclinical) depression. Our analyses show that effects might improve when CBT contains the components behavioral activation and challenging thoughts and also when the caregiver(s) are involved. However, the influential effects of these three moderators should be further tested in RCTs.

Specialized psychotherapies for adults with borderline personality disorder: A systematic review and meta-analysis.

OBJECTIVE: Borderline personality disorder affects up to 2% of the population and is associated with poor functioning, low quality of life and increased mortality. Psychotherapy is the treatment of choice, but it is unclear whether specialized psychotherapies (dialectical behavior therapy, mentalization-based treatment, transference-focused therapy and schema therapy) are more effective than non-specialized approaches (e.g. protocolized psychological treatment, general psychiatric management). The aim of this systematic review is to investigate the effectiveness of these psychotherapies. METHODS: PubMed, PsycINFO, CINAHL, EMBASE and CENTRAL were searched from inception to November 2017. Included randomized controlled trials were assessed on risk of bias and outcomes were meta-analyzed. Confidence in the results was assessed using the Grading of Recommendations Assessment, Development and Evaluation method. The review has been reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: A total of 20 studies with 1375 participants were included. Specialized psychotherapies, when compared to treatment as usual or community treatment by experts, were associated with a medium effect based on moderate quality evidence on overall borderline personality disorder severity (standardized mean difference = -0.59 [95% confidence interval: -0.90, -0.28]), and dialectical behavior therapy, when compared to treatment as usual, with a small to medium effect on self-injury (standardized mean difference = -0.40 [95% confidence interval: -0.66, -0.13]). Other effect estimates were often inconclusive, mostly due to imprecision. CONCLUSION: There is moderate quality evidence that specialized psychotherapies are effective in reducing overall borderline personality disorder severity. However, further research should identify which patient groups profit most of the specialized therapies.

Treatments for bulimia nervosa: a network meta-analysis.

BACKGROUND: Bulimia nervosa (BN) is a severe eating disorder that can be managed using a variety of treatments including pharmacological, psychological, and combination treatments. We aimed to compare their effectiveness and to identify the most effective for the treatment of BN in adults. METHODS: A search was conducted in Embase, Medline, PsycINFO, and Central from their inception to July 2016. Studies were included if they reported on treatments for adults who fulfilled diagnostic criteria for BN. Only randomised controlled trials (RCTs) that examined available psychological, pharmacological, or combination therapies licensed in the UK were included. We conducted a network meta-analysis (NMA) of RCTs. The outcome analysed was full remission at the end of treatment. RESULTS: We identified 21 eligible trials with 1828 participants involving 12 treatments, including wait list. The results of the NMA suggested that individual cognitive behavioural therapy (CBT) (specific to eating disorders) was most effective in achieving remission at the end of treatment compared with wait list (OR 3.89, 95% CrI 1.19-14.02), followed by guided cognitive behavioural self-help (OR 3.81, 95% CrI 1.51-10.90). Inconsistency checks did not identify any significant inconsistency between the direct and indirect evidence. CONCLUSIONS: The analysis suggested that the treatments that are most likely to achieve full remission are individual CBT (specific to eating disorders) and guided cognitive behavioural self-help, although no firm conclusions could be drawn due to the limited evidence base. There is a need for further research on the maintenance of treatment effects and the mediators of treatment outcome.

Paracrine cellular senescence exacerbates biliary injury and impairs regeneration.

Cellular senescence is a mechanism that provides an irreversible barrier to cell cycle progression to prevent undesired proliferation. However, under pathological circumstances, senescence can adversely affect organ function, viability and regeneration. We have developed a mouse model of biliary senescence, based on the conditional deletion of Mdm2 in bile ducts under the control of the Krt19 promoter, that exhibits features of biliary disease. Here we report that senescent cholangiocytes induce profound alterations in the cellular and signalling microenvironment, with recruitment of myofibroblasts and macrophages causing collagen deposition, TGFß production and induction of senescence in surrounding cholangiocytes and hepatocytes. Finally, we study how inhibition of TGFß-signalling disrupts the transmission of senescence and restores liver function. We identify cellular senescence as a detrimental mechanism in the development of biliary injury. Our results identify TGFß as a potential therapeutic target to limit senescence-dependent aggravation in human cholangiopathies.

Predicting suicide following self-harm: systematic review of risk factors and risk scales.

BACKGROUND: People with a history of self-harm are at a far greater risk of suicide than the general population. However, the relationship between self-harm and suicide is complex. AIMS: To undertake the first systematic review and meta-analysis of prospective studies of risk factors and risk assessment scales to predict suicide following self-harm. METHOD: We conducted a search for prospective cohort studies of populations who had self-harmed. For the review of risk scales we also included studies examining the risk of suicide in people under specialist mental healthcare, in order to broaden the scope of the review and increase the number of studies considered. Differences in predictive accuracy between populations were examined where applicable. RESULTS: Twelve studies on risk factors and 7 studies on risk scales were included. Four risk factors emerged from the meta-analysis, with robust effect sizes that showed little change when adjusted for important potential confounders. These included: previous episodes of self-harm (hazard ratio (HR) = 1.68, 95% CI 1.38-2.05, K = 4), suicidal intent (HR = 2.7, 95% CI 1.91-3.81, K = 3), physical health problems (HR = 1.99, 95% CI 1.16-3.43, K = 3) and male gender (HR = 2.05, 95% CI 1.70-2.46, K = 5). The included studies evaluated only three risk scales (Beck Hopelessness Scale (BHS), Suicide Intent Scale (SIS) and Scale for Suicide Ideation). Where meta-analyses were possible (BHS, SIS), the analysis was based on sparse data and a high heterogeneity was observed. The positive predictive values ranged from 1.3 to 16.7%. CONCLUSIONS: The four risk factors that emerged, although of interest, are unlikely to be of much practical use because they are comparatively common in clinical populations. No scales have sufficient evidence to support their use. The use of these scales, or an over-reliance on the identification of risk factors in clinical practice, may provide false reassurance and is, therefore, potentially dangerous. Comprehensive psychosocial assessments of the risks and needs that are specific to the individual should be central to the management of people who have self-harmed.

Practitioner Review: Treatments for Tourette syndrome in children and young people - a systematic review.

BACKGROUND: Tourette syndrome (TS) and chronic tic disorder (CTD) affect 1-2% of children and young people, but the most effective treatment is unclear. To establish the current evidence base, we conducted a systematic review of interventions for children and young people. METHODS: Databases were searched from inception to 1 October 2014 for placebo-controlled trials of pharmacological, behavioural, physical or alternative interventions for tics in children and young people with TS or CTD. Certainty in the evidence was assessed with the GRADE approach. RESULTS: Forty trials were included [pharmacological (32), behavioural (5), physical (2), dietary (1)]. For tics/global score there was evidence favouring the intervention from four trials of α2-adrenergic receptor agonists [clonidine and guanfacine, standardised mean difference (SMD) = -0.71; 95% CI -1.03, -0.40; N = 164] and two trials of habit reversal training (HRT)/comprehensive behavioural intervention (CBIT) (SMD = -0.64; 95% CI -0.99, -0.29; N = 133). Certainty in the effect estimates was moderate. A post hoc analysis combining oral clonidine/guanfacine trials with a clonidine patch trial continued to demonstrate benefit (SMD = -0.54; 95% CI -0.92, -0.16), but statistical heterogeneity was high. Evidence from four trials suggested that antipsychotic drugs improved tic scores (SMD = -0.74; 95% CI -1.08, -0.40; N = 76), but certainty in the effect estimate was low. The evidence for other interventions was categorised as low or very low quality, or showed no conclusive benefit. CONCLUSIONS: When medication is considered appropriate for the treatment of tics, the balance of clinical benefits to harm favours α2-adrenergic receptor agonists (clonidine and guanfacine) as first-line agents. Antipsychotics are likely to be useful but carry the risk of harm and so should be reserved for when α2-adrenergic receptor agonists are either ineffective or poorly tolerated. There is evidence that HRT/CBIT is effective, but there is no evidence for HRT/CBIT alone relative to combining medication and HRT/CBIT. There is currently no evidence to suggest that the physical and dietary interventions reviewed are sufficiently effective and safe to be considered as treatments.

NICE v. SIGN on psychosis and schizophrenia: same roots, similar guidelines, different interpretations.

A recent editorial claimed that the 2014 National Institute for Health and Care Excellence (NICE) guideline on psychosis and schizophrenia, unlike its equivalent 2013 Scottish Intercollegiate Guidelines Network (SIGN) guideline, is biased towards psychosocial treatments and against drug treatments. In this paper we underline that the NICE and SIGN guidelines recommend similar interventions, but that the NICE guideline has more rigorous methodology. Our analysis suggests that the authors of the editorial appear to have succumbed to bias themselves.

Psychological interventions for adults with bipolar disorder: systematic review and meta-analysis.

BACKGROUND: Psychological interventions may be beneficial in bipolar disorder. AIMS: To evaluate the efficacy of psychological interventions for adults with bipolar disorder. METHOD: A systematic review of randomised controlled trials was conducted. Outcomes were meta-analysed using RevMan and confidence assessed using the GRADE method. RESULTS: We included 55 trials with 6010 participants. Moderate-quality evidence associated individual psychological interventions with reduced relapses at post-treatment (risk ratio (RR) = 0.66, 95% CI 0.48-0.92) and follow-up (RR = 0.74, 95% CI 0.63-0.87), and collaborative care with a reduction in hospital admissions (RR = 0.68, 95% CI 0.49-0.94). Low-quality evidence associated group interventions with fewer depression relapses at post-treatment and follow-up, and family psychoeducation with reduced symptoms of depression and mania. CONCLUSIONS: There is evidence that psychological interventions are effective for people with bipolar disorder. Much of the evidence was of low or very low quality thereby limiting our conclusions. Further research should identify the most effective (and cost-effective) interventions for each phase of this disorder.

Clinical effectiveness and patient perspectives of different treatment strategies for tics in children and adolescents with Tourette syndrome: a systematic review and qualitative analysis.

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental condition characterised by chronic motor and vocal tics affecting up to 1% of school-age children and young people and is associated with significant distress and psychosocial impairment. OBJECTIVE: To conduct a systematic review of the benefits and risks of pharmacological, behavioural and physical interventions for tics in children and young people with TS (part 1) and to explore the experience of treatment and services from the perspective of young people with TS and their parents (part 2). DATA SOURCES: For the systematic reviews (parts 1 and 2), mainstream bibliographic databases, The Cochrane Library, education, social care and grey literature databases were searched using subject headings and text words for tic* and Tourette* from database inception to January 2013. REVIEW/RESEARCH METHODS: For part 1, randomised controlled trials and controlled before-and-after studies of pharmacological, behavioural or physical interventions in children or young people (aged < 18 years) with TS or chronic tic disorder were included. Mixed studies and studies in adults were considered as supporting evidence. Risk of bias associated with each study was evaluated using the Cochrane tool. When there was sufficient data, random-effects meta-analysis was used to synthesize the evidence and the quality of evidence for each outcome was assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. For part 2, qualitative studies and survey literature conducted in populations of children/young people with TS or their carers or in health professionals with experience of treating TS were included in the qualitative review. Results were synthesized narratively. In addition, a national parent/carer survey was conducted via the Tourettes Action website. Participants included parents of children and young people with TS aged under 18 years. Participants (young people with TS aged 10-17 years) for the in-depth interviews were recruited via a national survey and specialist Tourettes clinics in the UK. RESULTS: For part 1, 70 studies were included in the quantitative systematic review. The evidence suggested that for treating tics in children and young people with TS, antipsychotic drugs [standardised mean difference (SMD) -0.74, 95% confidence interval (CI) -1.08 to -0.41; n = 75] and noradrenergic agents [clonidine (Dixarit(®), Boehringer Ingelheim) and guanfacine: SMD -0.72, 95% CI -1.03 to -0.40; n = 164] are effective in the short term. There was little difference among antipsychotics in terms of benefits, but adverse effect profiles do differ. Habit reversal training (HRT)/comprehensive behavioural intervention for tics (CBIT) was also shown to be effective (SMD -0.64, 95% CI -0.99 to -0.29; n = 133). For part 2, 295 parents/carers of children and young people with TS contributed useable survey data. Forty young people with TS participated in in-depth interviews. Four studies were in the qualitative review. Key themes were difficulties in accessing specialist care and behavioural interventions, delay in diagnosis, importance of anxiety and emotional symptoms, lack of provision of information to schools and inadequate information regarding medication and adverse effects. LIMITATIONS: The number and quality of clinical trials is low and this downgrades the strength of the evidence and conclusions. CONCLUSIONS: Antipsychotics, noradrenergic agents and HRT/CBIT are effective in reducing tics in children and young people with TS. The balance of benefits and harms favours the most commonly used medications: risperidone (Risperdal(®), Janssen), clonidine and aripiprazole (Abilify(®), Otsuka). Larger and better-conducted trials addressing important clinical uncertainties are required. Further research is needed into widening access to behavioural interventions through use of technology including mobile applications ('apps') and video consultation. STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002059. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Perceptions of treatment for tics among young people with Tourette syndrome and their parents: a mixed methods study.

BACKGROUND: Tourette syndrome (TS) among young people is associated with psychosocial difficulties and parents play an important role in the management of the condition. Clinical guidelines have been developed for the treatment of TS and tics, but little is known about how young people and their parents perceive their treatment options or their desired outcomes of treatment. The aim of this study is to explore perceptions of treatments for tics among young people with TS and their parents. METHODS: In-depth interviews with 42 young people with TS and a mixed-methods, online survey of 295 parents of young people with TS. Participant recruitment was conducted through Tourettes Action (TA): a non-profit UK organisation for the support of people with TS. Interview transcripts were analysed using thematic analysis and responses to survey open-ended questions were analysed using content analysis. Triangulation of qualitative and quantitative data from the parents' survey and qualitative data from the interviews with young people was used to increase the validity and depth of the findings. RESULTS: A strong theme was the perception that health professionals have limited knowledge of TS and its treatment. Medication was a common treatment for tics and both young people and parents described benefits of medication. However, adverse effects were frequently described and these were a common reason for stopping medication among young people. Aripiprazole was viewed most positively. Access to behavioural interventions for tics was limited and 76% of parents wanted this treatment to be available for their child. Some young people had reservations about the effectiveness or practicality of behavioural interventions. Reduction and abolition of tics were desired outcomes of treatment, but both parents and young people also identified the importance of increasing control over tics and reducing anxiety-related symptoms. For young people, managing the urge to tic was an important outcome of treatment. CONCLUSIONS: The results suggest a need for more training in the identification and management of TS and wider availability of behavioural treatments. Clinical trials could explore the effectiveness of Aripiprazole used in combination with psycho-educational interventions to reduce anxiety and promote a sense of control.

Interventions to improve the experience of caring for people with severe mental illness: systematic review and meta-analysis.

BACKGROUND: Informal caregiving is an integral part of the care of people with severe mental illness, but the support needs of those providing such care are not often met. AIMS: To determine whether interventions provided to people caring for those with severe mental illness improve the experience of caring and reduce caregiver burden. METHOD: We conducted a systematic review and meta-analyses of randomised controlled trials (RCTs) of interventions delivered by health and social care services to informal carers (i.e. family or friends who provide support to someone with severe mental illness). RESULTS: Twenty-one RCTs with 1589 carers were included in the review. There was evidence suggesting that the carers' experience of care was improved at the end of the intervention by psychoeducation (standardised mean difference -1.03, 95% CI -1.69 to -0.36) and support groups (SMD = -1.16, 95% CI -1.96 to -0.36). Psychoeducation had a benefit on psychological distress more than 6 months later (SMD = -1.79, 95% CI -3.01 to -0.56) but not immediately post-intervention. Support interventions had a beneficial effect on psychological distress at the end of the intervention (SMD = -0.99, 95% CI -1.48 to -0.49) as did problem-solving bibliotherapy (SMD = -1.57, 95% CI -1.79 to -1.35); these effects were maintained at follow-up. The quality of the evidence was mainly low and very low. Evidence for combining these interventions and for self-help and self-management was inconclusive. CONCLUSIONS: Carer-focused interventions appear to improve the experience of caring and quality of life and reduce psychological distress of those caring for people with severe mental illness, and these benefits may be gained in first-episode psychosis. Interventions for carers should be considered as part of integrated services for people with severe mental health problems.

Computerised therapies for anxiety and depression in children and young people: a systematic review and meta-analysis.

One quarter of children and young people (CYP) experience anxiety and/or depression before adulthood, but treatment is sometimes unavailable or inadequate. Self-help interventions may have a role in augmenting treatment and this work aimed to systematically review the evidence for computerised anxiety and depression interventions in CYP aged 5-25 years old. Databases were searched for randomised controlled trials and 27 studies were identified. For young people (12-25 years) with risk of diagnosed anxiety disorders or depression, computerised CBT (cCBT) had positive effects for symptoms of anxiety (SMD -0.77, 95% CI -1.45 to -0.09, k = 6, N = 220) and depression (SMD -0.62, 95% CI -1.13 to -0.11, k = 7, N = 279). In a general population study of young people, there were small positive effects for anxiety (SMD -0.15, 95% CI -0.26 to -0.03; N = 1273) and depression (SMD -0.15, 95% CI -0.26 to -0.03; N = 1280). There was uncertainty around the effectiveness of cCBT in children (5-11 years). Evidence for other computerised interventions was sparse and inconclusive. Computerised CBT has potential for treating and preventing anxiety and depression in clinical and general populations of young people. Further program development and research is required to extend its use and establish its benefit in children.