Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

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.

Recovery-based staff training intervention within mental health rehabilitation units: a two-stage analysis using realistic evaluation principles and framework approach.

BACKGROUND: Long-term change in recovery-based practice in mental health rehabilitation is a research priority. METHODS: We used a qualitative case study analysis using a blend of traditional 'framework' analysis and 'realist' approaches to carry out an evaluation of a recovery-focused staff training intervention within three purposively selected mental health rehabilitation units. We maximised the validity of the data by triangulating multiple data sources. RESULTS: We found that organisational culture and embedding of a change management programme in routine practice were reported as key influences in sustaining change in practice. The qualitative study generated 10 recommendations on how to achieve long-term change in practice including addressing pre-existing organisational issues and synergising concurrent change programmes. CONCLUSIONS: We propose that a recovery-focused staff training intervention requires clear leadership and integration with any existing change management programmes to facilitate sustained improvements in routine practice.

Clinical outcomes and costs for people with complex psychosis; a naturalistic prospective cohort study of mental health rehabilitation service users in England.

BACKGROUND: Mental health rehabilitation services in England focus on people with complex psychosis. This group tend to have lengthy hospital admissions due to the severity of their problems and, despite representing only 10-20 % of all those with psychosis, they absorb 25-50 % of the total mental health budget. Few studies have investigated the effectiveness of these services and there is little evidence available to guide clinicians working in this area. As part of a programme of research into inpatient mental health rehabilitation services, we carried out a prospective study to investigate longitudinal outcomes and costs for patients of these services and the predictors of better outcome. METHOD: Inpatient mental health rehabilitation services across England that scored above average (median) on a standardised quality assessment tool used in a previous national survey were eligible for the study. Unit quality was reassessed and costs of care and patient characteristics rated using standardised tools at recruitment. Multivariable regression modelling was used to investigate the relationship between service quality, patient characteristics and the following clinical outcomes at 12 month follow-up: social function; length of admission in the rehabiliation unit; successful community discharge (without readmission or community placement breakdown) and costs of care. RESULTS: Across England, 50 units participated and 329 patients were followed over 12 months (94 % of those recruited). Service quality was not associated with patients' social function or length of admission (median 16 months) at 12 months but most patients were successfully discharged (56 %) or ready for discharge (14 %), with associated reductions in the costs of care. Factors associated with successful discharge were the recovery orientation of the service (OR 1.04, 95 % CI 1.00-1.08), and patients' activity (OR 1.03, 95 % CI 1.01-1.05) and social skills (OR 1.13, 95 % CI 1.04-1.24) at recruitment. CONCLUSION: Inpatient mental health rehabilitation services in England are able to successfully discharge over half their patients within 18 months, reducing the costs of care for this complex group. Provision of recovery orientated practice that promotes patients' social skills and activities may further enhance the effectiveness of these services.

Barriers to the sustainability of an intervention designed to improve patient engagement within NHS mental health rehabilitation units: a qualitative study nested within a randomised controlled trial.

BACKGROUND: We undertook a cluster randomised controlled trial to assess the effectiveness of a staff training intervention to improve patient engagement in activities in inpatient mental health rehabilitation units. Concurrently, we undertook a qualitative study to investigate the experiences of staff within the intervention units and the contextual issues that may have influenced the effectiveness of the intervention. METHOD: We conducted focus groups with staff working in the inpatient units that received the intervention, sampled using a maximum variation strategy. RESULTS: The intervention was accepted by staff. However, the skills gained, and changes to the unit's processes and structures that were agreed with the intervention team were not sustained after they left. The main reasons for this were a) external factors (economic recession, resource limitations); b) organisation level factors (lack of senior staff support; competing priorities); c) limitations of the intervention itself (length of intensive training period; reinforcement of skills). CONCLUSION: This study illustrates some of the inter-related factors which operate at different levels within and outside of NHS organisations that may impact on the success of complex interventions. These factors need to be considered when designing interventions to ensure adequate buy-in from senior staff. TRIAL REGISTRATION: Current Controlled Trials ISRCTN25898179 (Registered 23 April 2010).

Single-dose psilocybin for U.S. military Veterans with severe treatment-resistant depression - A first-in-kind open-label pilot study.

BACKGROUND: The enduring and severe depression often suffered by Veterans causes immense suffering and is associated with high rates of suicide and disability. This is the first study to evaluate the efficacy and safety of psilocybin in Veterans with severe treatment-resistant depression (TRD). METHODS: 15 Veterans with severe TRD (major depressive episode failing to respond to ≥5 treatments, or lasting >2 years) received 25 mg of psilocybin. Primary outcome was change in Montgomery-Åsberg Depression Rating scale (MADRS) at 3 weeks posttreatment. Response was defined s ≥ 50 % reduction in MADRS, and remission as ≤10 MADRS score. Psychedelic experience was assessed using the Five-Dimensional Altered States of Consciousness scale (5D-ASC). Safety measures included assessment of suicidality and adverse events. Participants on antidepressants were tapered to avoid drug interactions. RESULTS: Of 15 participants, 60 % met response and 53 % met remission criteria at Week 3. At 12 weeks, 47 % maintained response, and 40 % remission. Co-morbid PTSD did not significantly influence study outcomes. The psychedelic experience reported in 5D-ASC did not correlate with response. Participants judged to need antidepressants were restarted and considered non-responders from that timepoint (n = 4). No unexpected adverse events occurred. LIMITATIONS: Limitations include the small sample size, and the uncontrolled and unblinded nature of the study. CONCLUSIONS: In this first study on psilocybin for Veterans with severe TRD, a surprising response and remission was seen. Many Veterans had PTSD though no moderating impact of response was observed. The degree of psychedelic experience did not correlate with depression changes. Further study is warranted. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04433858.

Service quality and clinical outcomes: an example from mental health rehabilitation services in England.

BACKGROUND: Current health policy assumes better quality services lead to better outcomes. AIMS: To investigate the relationship between quality of mental health rehabilitation services in England, local deprivation, service user characteristics and clinical outcomes. METHOD: Standardised tools were used to assess the quality of mental health rehabilitation units and service users' autonomy, quality of life, experiences of care and ratings of the therapeutic milieu. Multiple level modelling investigated relationships between service quality, service user characteristics and outcomes. RESULTS: A total of 52/60 (87%) National Health Service trusts participated, comprising 133 units and 739 service users. All aspects of service quality were positively associated with service users' autonomy, experiences of care and therapeutic milieu, but there was no association with quality of life. CONCLUSIONS: Quality of care is linked to better clinical outcomes in people with complex and longer-term mental health problems. Thus, investing in quality is likely to show real clinical gains.

Training early psychosis community clinicians in CBT for psychosis: Implementation and feasibility.

OBJECTIVE: Cognitive behavioural therapy (CBT) has demonstrated efficacy for treating of psychotic symptoms and is recommended as an evidence-based practice (EBP) in early psychosis services. Despite this recommendation, there is limited information about the feasibility of training community clinicians, working in an early psychosis service, to competence in the delivery of this intervention. METHOD: Fifty clinicians working in an early psychosis service across five programs in Northern California were trained in CBT for psychosis (CBTp) between 2010 and 2014. Following the training, clinicians attended weekly group consultation and submitted taped sessions for review. Tapes were rated for competency using the Cognitive Therapy Scale-Revised (CTS-R). Clinicians who achieved competence were engaged in a train-the-trainer model to support ongoing sustainability of the training program. RESULTS: Data from 40 clinicians were reviewed for achievement of competence. Over the training period 18 clinicians achieved competence while 20 clinicians left the service before achieving competence and 12 were still in the process of achieving competence at the point of data analysis. It took on average 54 weeks (range 17-130 weeks) and an average of six tape reviews (range 3-18) to train clinicians to competency. CONCLUSIONS: Community clinicians working in an early psychosis program can be trained to competence in CBTp following an initial didactic period and ongoing weekly group consultation, although staff turnover hindered implementation. Challenges and opportunities for future implementation in community sites are presented in the context of further expansion of early psychosis services in the United States.

Clinical effectiveness of a staff training intervention in mental health inpatient rehabilitation units designed to increase patients' engagement in activities (the Rehabilitation Effectiveness for Activities for Life [REAL] study): single-blind, cluster-randomised controlled trial.

BACKGROUND: Mental health inpatient rehabilitation services focus on people with complex psychosis who have, for example, treatment-refractory symptoms, cognitive impairment, and severe negative symptoms, which impair functioning and require lengthy admission. Engagement in activities could lead to improvement in negative symptoms and function, but few trials have been done. We aimed to investigate the effectiveness of a staff training intervention to increase patients' engagement in activities. METHODS: We did a single-blind, two-arm, cluster-randomised controlled trial in 40 mental health inpatient rehabilitation units across England. Units were randomly allocated to either a manual-based staff training programme delivered by a small intervention team (intervention group, n=20) or standard care (control group, n=20). The primary outcome was patients' engagement in activities 12 months after randomisation, measured with the time use diary. With this measure, both the degree of engagement in an activity and its complexity are recorded four times a day for a week, rated on a scale of 0-4 for every period (maximum score of 112). Analysis was by intention-to-treat. Random-effects models were used to compare outcomes between study groups. Cost-effectiveness was assessed by combining service costs with the primary outcome. This study is registered with Current Controlled Trials (ISRCTN25898179). FINDINGS: Patients' engagement in activities did not differ between study groups (coefficient 1·44, 95% CI -1·35 to 4·24). An extra £101 was needed to achieve a 1% increase in patients' engagement in activities with the study intervention. INTERPRETATION: Our training intervention did not increase patients' engagement in activities after 12 months of follow-up. This failure could be attributable to inadequate implementation of the intervention, a high turnover of patients in the intervention units, competing priorities on staff time, high levels of patients' morbidity, and ceiling effects because of the high quality of standard care delivered. Further studies are needed to identify interventions that can improve outcomes for people with severe and complex psychosis. FUNDING: National Institute for Health Research.