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.