Cost-effectiveness of psilocybin-assisted therapy for severe depression: exploratory findings from a decision analytic model.

BACKGROUND: There is growing evidence to support the use of the psychedelic drug psilocybin for difficult-to-treat depression. This paper compares the cost-effectiveness of psilocybin-assisted psychotherapy (PAP) with conventional medication, cognitive behavioural therapy (CBT), and the combination of conventional medication and CBT. METHODS: A decision model simulated patient events (response, remission, and relapse) following treatment. Data on probabilities, costs and quality-adjusted life years (QALYs) were derived from previous studies or from best estimates. Expected healthcare and societal costs and QALYs over a 6-month time period were calculated. Sensitivity analyses were used to address uncertainty in parameter estimates. RESULTS: The expected healthcare cost of PAP varied from £6132 to £7652 depending on the price of psilocybin. This compares to £3528 for conventional medication alone, £4250 for CBT alone, and £4197 for their combination. QALYs were highest for psilocybin (0.310), followed by CBT alone (0.283), conventional medication alone (0.278), and their combination (0.287). Psilocybin was shown to be cost-effective compared to the other therapies when the cost of therapist support was reduced by 50% and the psilocybin price was reduced from its initial value to £400 to £800 per person. From a societal perspective, psilocybin had improved cost-effectiveness compared to a healthcare perspective. CONCLUSIONS: Psilocybin has the potential to be a cost-effective therapy for severe depression. This depends on the level of psychological support that is given to patients receiving psilocybin and the price of the drug itself. Further data on long-term outcomes are required to improve the evidence base.

Treating common mental disorder including psychotic experiences in the primary care improving access to psychological therapies programme (the TYPPEX study): protocol for a stepped wedge cluster randomised controlled trial with nested economic and process evaluation of a training package for therapists.

INTRODUCTION: At least one in four people treated by the primary care improving access to psychological therapies (IAPT) programme in England experiences distressing psychotic experiences (PE) in addition to common mental disorder (CMD). These individuals are less likely to achieve recovery. IAPT services do not routinely screen for nor offer specific treatments for CMD including PE. The Tailoring evidence-based psychological therapY for People with common mental disorder including Psychotic EXperiences study will evaluate the clinical and cost-effectiveness of an enhanced training for cognitive behavioural therapists that aims to address this clinical gap. METHODS AND ANALYSIS: This is a multisite, stepped-wedge cluster randomised controlled trial. The setting will be IAPT services within three mental health trusts. The participants will be (1) 56-80 qualified IAPT cognitive behavioural therapists and (2) 600 service users who are triaged as appropriate for cognitive behavioural therapy in an IAPT service and have PE according to the Community Assessment of Psychic Experiences-Positive 15-items Scale. IAPT therapists will be grouped into eight study clusters subsequently randomised to the control-intervention sequence. We will obtain pseudonymous clinical outcome data from IAPT clinical records for eligible service users. We will invite service users to complete health economic measures at baseline, 3, 6, 9 and 12-month follow-up. The primary outcome will be the proportion of patients with common mental disorder psychotic experiences who have recovered by the end of treatment as measured by the official IAPT measure for recovery. ETHICS AND DISSEMINATION: The study received the following approvals: South Central-Berkshire Research Ethics Committee on 28 April 2020 (REC reference 20/SC/0135) and Health Research Authority (HRA) on 23 June 2020. An amendment was approved by the Ethics Committee on 01 October 2020 and HRA on 27 October 2020. Results will be made available to patients and the public, the funders, stakeholders in the IAPT services and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN93895792.

On Dimensionality, Measurement Invariance, and Suitability of Sum Scores for the PHQ-9 and the GAD-7.

In psychiatry, severity of mental health conditions and their change over time are usually measured via sum scores of items on psychometric scales. However, inferences from such scores can be biased if psychometric properties such as unidimensionality and temporal measurement invariance for instruments are not met. Here, we aimed to evaluate these properties for common measures of depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder Assessment-7) in a large clinical sample (N = 22,362) undergoing psychotherapy. In addition, we tested consistency in dimensionality results across different methods (parallel analysis, factor analysis, explained common variance, the partial credit model, and the Mokken model). Results showed that while both Patient Health Questionnaire-9 and Generalized Anxiety Disorder Assessment-7 are multidimensional instruments with highly correlated factors, there is justification for sum scores as measures of severity. Temporal measurement invariance across 10 therapy sessions was evaluated. Strict temporal measurement invariance was established in both scales, allowing researchers to compare sum scores as severity measures across time.

Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

BACKGROUND: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting. METHODS: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery. RESULTS: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria). CONCLUSIONS: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.

More sensitive identification of psychotic experiences in common mental disorder by primary mental healthcare services - effect on prevalence and recovery: casting the net wider.

BACKGROUND: Psychotic experiences may emerge in more severe cases of common mental disorders (CMD). Previous work identified that 30% of patients treated by mental health services in primary healthcare, specifically the Improving Access to Psychological Therapies (IAPT) programme in England, reported psychotic experiences, began treatment with more severe CMD and were less likely to reach recovery. AIMS: To replicate our previous assessment of psychotic experiences in the IAPT programme using a more sensitive threshold and determine its impact on the prevalence of psychotic experience and likelihood of recovery. Additionally, to compare recovery rates between patients with and without psychotic experiences at the end of therapy. METHOD: The Community Assessment of Psychic Experiences (CAPE-P15) with a cut-off of 1.30 was used to determine the prevalence of psychotic experiences. Recovery rates were determined using measures collected in the IAPT programme for depression (PHQ-9) and anxiety (GAD-7). Multi-group growth models estimated improvement trajectories. RESULTS: In total, 2042 patients with CMD completed the CAPE-P15. The mean age was 39.8. The prevalence of psychotic experiences was 18% higher when using a lower threshold. The recovery rate for patients with psychotic experiences was lower (36%) than for those without (64%). Despite sharing similar improvement trajectories, the higher initial severity of CMD among patients with psychotic experiences impeded likelihood of recovery. CONCLUSIONS: As psychotic experiences may be a marker of severity in CMD, the benefits of identifying these in IAPT populations may also apply to patients with milder experiences. Further investigation of the consequential demands on service provision and how this would affect clinical practice is recommended.

Prevalence of and recovery from common mental disorder including psychotic experiences in the UK Primary Care Improving Access to Psychological Therapies (IAPT) Programme.

BACKGROUND: Psychotic experiences (PE) may co-occur with common mental disorders (CMD), such as depression and anxiety. However, we know very little about the prevalence of and recovery from PE in primary mental health care settings, such as the Improving Access to Psychological Therapies (IAPT) services in the UK National Health Service (NHS), where most CMD are treated. METHODS: We used the Community Assessment of Psychic Experiences - Positive 15-item Scale (CAPE-P15) to determine the prevalence of PE in patients receiving treatment from IAPT services. Patient-reported measures of depression (PHQ-9) and anxiety (GAD-7) are routinely collected and establish recovery in IAPT services. We studied recovery rates according to the absence and presence of PE. Multi-group growth models estimated improvement trajectories for each group. RESULTS: A total of 2,042 patients with CMD completed the CAPE-P15. The mean age was 39.8. The overall prevalence of PE was 29.68%. The recovery rate was 27.43% compared to 62.08% for those without PE. Although patients with or without PE shared similar improvement trajectories, the initial severity of patients with PE impeded their likelihood of recovery. LIMITATIONS: We mirrored routine data collection in IAPT services, including self-report questionnaires that may affect valid reporting of symptoms. Missing data in the calculation of improvement trajectories may reduce generalisability. CONCLUSIONS: At least one in four patients receiving treatment from IAPT services in primary care experience CMD and PE. This significant group of people experience a lower recovery rate, with adverse implications not only for them but also for efficiency of services.

Psychological interventions for people with psychotic experiences: A systematic review and meta-analysis of controlled and uncontrolled effectiveness and economic studies.

OBJECTIVE: Many people with psychotic experiences do not develop psychotic disorders, yet those who seek help demonstrate high clinical complexity and poor outcomes. In this systematic review and meta-analysis, we evaluated the effectiveness and cost-effectiveness of psychological interventions for people with psychotic experiences. METHOD: We searched 13 databases for studies of psychological interventions for adults with psychotic experiences, but not psychotic disorders. Our outcomes were the proportion of participants remitting from psychotic experiences (primary); changes in positive and negative psychotic symptoms, depression, anxiety, functioning, distress, and quality of life; and economic outcomes (secondary). We analysed results using multilevel random-effects meta-analysis and narrative synthesis. RESULTS: A total of 27 reports met inclusion criteria. In general, there was no strong evidence for the superiority of any one intervention. Five studies reported on our primary outcome, though only two reports provided randomised controlled trial evidence that psychological intervention (specifically, cognitive behavioural therapy) promoted remission from psychotic experiences. For secondary outcomes, we could only meta-analyse trials of cognitive behavioural therapy. We found that cognitive behavioural therapy was more effective than treatment as usual for reducing distress (pooled standardised mean difference: -0.24; 95% confidence interval = [-0.37, -0.10]), but no more effective than the control treatment for improving any other outcome. Individual reports indicated that cognitive behavioural therapy, mindfulness-based cognitive therapy, sleep cognitive behavioural therapy, systemic therapy, cognitive remediation therapy, and supportive treatments improved at least one clinical or functional outcome. Four reports included economic evaluations, which suggested cognitive behavioural therapy may be cost-effective compared with treatment as usual. CONCLUSION: Our meta-analytic findings were primarily null, with the exception that cognitive behavioural therapy may reduce the distress associated with psychotic experiences. Our analyses were limited by scarcity of studies, small samples and variable study quality. Several intervention frameworks showed preliminary evidence of positive outcomes; however, the paucity of consistent evidence for clinical and functional improvement highlights a need for further research into psychological treatments for psychotic experiences. PROSPERO PROTOCOL REGISTRATION NUMBER: CRD42016033869.

Revisiting CAPE-P15 cut-off values to increase sensitivity for detecting psychotic experiences in primary care.

Psychotic experiences (PE) co-occur with depression and anxiety, and indicate severity of general mental distress. Identifying PE in primary care mental health settings may facilitate access to evidence-based interventions. The Community Assessment of Psychic Experiences - Positive 15-items Scale (CAPE-P15) has shown promise in detecting those at ultra-high risk of developing psychosis. Based on a sample of 1131 individuals with common mental disorder we propose high-sensitivity thresholds of the CAPE-P15 to broaden its application across clinical settings.

Psychological interventions for people with psychotic experiences: protocol for a systematic review and meta-analysis.

BACKGROUND: Many people who have common mental disorders, such as depression and anxiety, also have some psychotic experiences. These experiences are associated with higher clinical complexity, poor treatment response, and negative clinical outcomes. Psychological interventions have the potential to improve outcomes for people with psychotic experiences. The aims of this systematic review are to (1) synthesise the evidence on the effectiveness and cost-effectiveness of psychological interventions to reduce psychotic experiences and their associated distress and (2) identify key components of effective interventions. METHODS: Our search strategy will combine terms for (1) psychological interventions, (2) psychotic experiences, and (3) symptoms associated with psychotic experiences. We will search the following online databases: MEDLINE, Embase, PsycINFO, all Cochrane databases, British Nursing Index (BNI), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Management Information Consortium (HMIC), Education Resources Information Center (ERIC), and EconLit. Our primary outcome is the proportion of people who recovered or remitted from psychotic experiences after the intervention. Our secondary outcomes are changes in positive psychotic symptoms, negative psychotic symptoms, depression, anxiety, functioning (including social, occupational, and academic), quality of life, and cost-effectiveness. Two independent reviewers will judge each study against pre-specified inclusion and exclusion criteria and will extract study characteristics, outcome data, and intervention components. Risk of bias and methodological quality will be assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies and the Drummond Checklist. Results will be synthesised using random-effects meta-analysis and narrative synthesis. DISCUSSION: The identification of effective psychological interventions and of specific components associated with intervention effectiveness will augment existing evidence that can inform the development of a new, tailored intervention to improve outcomes related to psychotic symptoms, anxiety and depression, distress, functioning, and quality of life. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016033869.

Coproducing healthcare service improvement for people with common mental health disorders including psychotic experiences: a study protocol of a multiperspective qualitative study.

INTRODUCTION: Some people, who have common mental health disorders such as depression and anxiety, also have some psychotic experiences. These individuals may experience a treatment gap: their symptoms neither reach the increasingly high threshold for secondary care, nor do they receive full benefit from current interventions offered by the Improving Access to Psychological Therapies (IAPT) programme. The result may be poorer clinical and functional outcomes. A new talking therapy could potentially benefit this group. Informed by principles of coproduction, this study will seek the views of service users and staff to inform the design and development of such a therapy. METHODS AND ANALYSIS: Semistructured interviews will be conducted with IAPT service users, therapists and managers based in three different geographical areas in England. Our sample will include (1) approximately 15 service users who will be receiving therapy or will have completed therapy at the time of recruitment, (2) approximately 15 service users who initiated treatment but withdrew, (3) approximately 15 therapists each with at least 4-month experience in a step-3 IAPT setting and (4) three IAPT managers. Data analysis will be based on the constant comparative method. ETHICS AND DISSEMINATION: The study has been approved by the London Harrow Research Ethics Committee (reference: 18/LO/0642), and all National Health Service Trusts have granted permissions to conduct the study. Findings will be published in peer-reviewed academic journals, and presented at academic conferences. We will also produce a 'digest' summary of the findings, which will be accessible, visual and freely available.