Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

The serum metabolomic profile of a distinct, inflammatory subtype of acute psychosis.

A range of studies suggest that a proportion of psychosis may have an autoimmune basis, but this has not translated through into clinical practice-there is no biochemical test able to accurately identify psychosis resulting from an underlying inflammatory cause. Such a test would be an important step towards identifying who might require different treatments and have the potential to improve outcomes for patients. To identify novel subgroups within patients with acute psychosis we measured the serum nuclear magnetic resonance (NMR) metabolite profiles of 75 patients who had identified antibodies (anti-glycine receptor [GlyR], voltage-gated potassium channel [VGKC], Contactin-associated protein-like 2 [CASPR2], leucine-rich glioma inactivated 1 [LGI1], N-methyl-D-aspartate receptor [NMDAR] antibody) and 70 antibody negative patients matched for age, gender, and ethnicity. Clinical symptoms were assessed using the positive and negative syndrome scale (PANSS). Unsupervised principal component analysis identified two distinct biochemical signatures within the cohort. Orthogonal partial least squared discriminatory analysis revealed that the serum metabolomes of NMDAR, LGI1, and CASPR2 antibody psychosis patients were indistinct from the antibody negative control group while VGKC and GlyR antibody patients had significantly decreased lipoprotein fatty acids and increased amino acid concentrations. Furthermore, these patients had more severe presentation with higher PANSS scores than either the antibody negative controls or the NMDAR, LGI1, and CASPR2 antibody groups. These results suggest that a proportion of patients with acute psychosis have a distinct clinical and biochemical phenotype that may indicate an inflammatory subtype.

Cost and quality-of-life impacts of community treatment orders (CTOs) for patients with psychosis: economic evaluation of the OCTET trial.

PURPOSE: Current RCT and meta-analyses have not found any effect of community treatment orders (CTOs) on hospital or social outcomes. Assumed positive impacts of CTOs on quality-of-life outcomes and reduced hospital costs are potentially in conflict with patient autonomy. Therefore, an analysis of the cost and quality-of-life consequences of CTOs was conducted within the OCTET trial. METHODS: The economic evaluation was carried out comparing patients (n = 328) with psychosis discharged from involuntary hospitalisation either to treatment under a CTO (CTO group) or voluntary status via Section 17 leave (non-CTO group) from the health and social care and broader societal perspectives (including cost implication of informal family care and legal procedures). Differences in costs and outcomes defined as quality-adjusted life years (QALYs) based on the EQ-5D-3L or capability-weighted life years (CWLYs) based on the OxCAP-MH were assessed over 12 months (£, 2012/13 tariffs). RESULTS: Mean total costs from the health and social care perspective [CTO: £35,595 (SD: £44,886); non-CTO: £36,003 (SD: £41,406)] were not statistically significantly different in any of the analyses or cost categories. Mental health hospitalisation costs contributed to more than 85% of annual health and social care costs. Informal care costs were significantly higher in the CTO group, in which there were also significantly more manager hearings and tribunals. No difference in health-related quality of life or capability wellbeing was found between the groups. CONCLUSION: CTOs are unlikely to be cost-effective. No evidence supports the hypothesis that CTOs decrease hospitalisation costs or improve quality of life. Future decisions should consider impacts outside the healthcare sector such as higher informal care costs and legal procedure burden of CTOs.

What does being on a community treatment orders entail? A 3-year follow-up of the OCTET CTO cohort.

PURPOSE: Community Treatment Orders lack evidence of effectiveness. Very little is known about how they are used in practice and over time in terms of what it obliges patients to do and the judicial threshold for remaining on an order. AIMS: To investigate CTO implementation in England in terms of the use of specified conditions, and judicial hearings; whether these change over time, and; the level of continued coercion. METHOD: 36-month observational prospective study of patients on CTO in the OCTET follow-up study. RESULTS: The number of CTO conditions remained stable over time but consolidated around medication adherence and remaining in contact with services. Ten percent of Mental Health Tribunal Hearings and only 1 percent of Hospital Managers Hearings resulted in discharge. Twenty-seven percent of patients experienced more than one CTO episode and eighteen percent remained under compulsion until the end of follow-up. CONCLUSIONS: CTOs seem to be used primarily to oblige patients to take medication and stay in contact with services. There is agreement between clinical and legal judgements about their appropriateness and threshold for use. A pattern of continuous coercion for a significant group of patients raises concerns. If CTOs are to be continued to be imposed, their use should be carefully monitored with further cohort studies with long-term follow-up.

Recall of patients on community treatment orders over three years in the OCTET CTO cohort.

BACKGROUND: Randomised studies consistently show that Community Treatment Orders (CTOs) do not have the intended effect of preventing relapse and readmissions of patients with severe and enduring mental illness. Critics suggest this in part can be explained by RCTs studying newly introduced CTO regimes and that patients therefore were not brought back to hospital for short-term observations ('recall') as frequently as intended. Our purpose was (i) to test the hypothesis that CTO practice as regards recall of patients to hospital in England and Wales was as rigorous under the OCTET trial period as in current routine use and (ii) to investigate the reasons for and outcomes of recalls and whether this changed over time. METHOD: Thirty six-month observational prospective study of 198 patients in the OCTET Follow-up Study. RESULTS: Forty percent of patients were recalled, 19 % more than once. This is in line with current national use. Deterioration in clinical condition was the most common reason for recalls (49 %), and 68 % of recalls resulted in revocation of the order (i.e., retention in hospital under compulsion). This pattern remained stable over time. CONCLUSION: The use of recall cannot explain why RCTs have not confirmed any benefits from CTOs, and their continued use should be reconsidered. TRIAL REGISTRATION: The OCTET Trial was retrospectively registered on 12 November 2009 ( ISRCTN73110773 ).

A randomised controlled trial of time-limited individual placement and support: IPS-LITE trial.

BACKGROUND: Individual placement and support (IPS) has been repeatedly demonstrated to be the most effective form of mental health vocational rehabilitation. Its no-discharge policy plus fixed caseloads, however, makes it expensive to provide. AIMS: To test whether introducing a time limit for IPS would significantly alter its clinical effectiveness and consequently its potential cost-effectiveness. METHOD: Referrals to an IPS service were randomly allocated to either standard IPS or to time-limited IPS (IPS-LITE). IPS-LITE participants were referred back to their mental health teams if still unemployed at 9 months or after 4 months employment support. The primary outcome at 18 months was working for 1 day. Secondary outcomes comprised other vocational measures plus clinical and social functioning. The differential rates of discharge were used to calculate a notional increased capacity and to model potential rates and costs of employment. RESULTS: A total of 123 patients were randomised and data were collected on 120 patients at 18 months. The two groups (IPS-LITE = 62 and IPS = 61) were well matched at baseline. Rates of employment were equal at 18 months (IPS-LITE = 24 (41%) and IPS = 27 (46%)) at which time 57 (97%) had been discharged from the IPS-LITE service and 16 (28%) from IPS. Only 11 patients (4 IPS-LITE and 7 IPS) obtained their first employment after 9 months. There were no significant differences in any other outcomes. IPS-LITE discharges generated a potential capacity increase of 46.5% compared to 12.7% in IPS which would translate into 35.8 returns to work in IPS-LITE compared to 30.6 in IPS over an 18-month period if the rates remained constant. CONCLUSIONS: IPS-LITE is equally effective to IPS and only minimal extra employment is gained by persisting beyond 9 months. If released capacity is utilised with similar outcomes, IPS-LITE results in an increase by 17% in numbers gaining employment within 18 months compared to IPS and will increase with prolonged follow-up. IPS-LITE may be more cost-effective and should be actively considered as an alternative within public services.

Community treatment orders for patients with psychosis (OCTET): a randomised controlled trial.

BACKGROUND: Compulsory supervision outside hospital has been developed internationally for the treatment of mentally ill people following widespread deinstitutionalisation but its efficacy has not yet been proven. Community treatment orders (CTOs) for psychiatric patients became available in England and Wales in 2008. We tested whether CTOs reduce admissions compared with use of Section 17 leave when patients in both groups receive equivalent levels of clinical contact but different lengths of compulsory supervision. METHODS: OCTET is a non-blinded, parallel-arm randomised controlled trial. We postulated that patients with a diagnosis of psychosis discharged from hospital on CTOs would have a lower rate of readmission over 12 months than those discharged on the pre-existing Section 17 leave of absence. Eligible patients were those involuntarily admitted to hospital with a diagnosis of psychosis, aged 18-65 years, who were deemed suitable for supervised outpatient care by their clinicians. Consenting patients were randomly assigned (1:1 ratio) to be discharged from hospital either on CTO or Section 17 leave. Randomisation used random permuted blocks with lengths of two, four, and six, and stratified for sex, schizophrenic diagnosis, and duration of illness. Research assistants, treating clinicians, and patients were aware of assignment to randomisation group. The primary outcome measure was whether or not the patient was admitted to hospital during the 12-month follow-up period, analysed with a log-binomial regression model adjusted for stratification factors. We did all analyses by intention to treat. This trial is registered, number ISRCTN73110773. FINDINGS: Of 442 patients assessed, 336 patients were randomly assigned to be discharged from hospital either on CTO (167 patients) or Section 17 leave (169 patients). One patient withdrew directly after randomisation and two were ineligible, giving a total sample of 333 patients (166 in the CTO group and 167 in the Section 17 group). At 12 months, despite the fact that the length of initial compulsory outpatient treatment differed significantly between the two groups (median 183 days CTO group vs 8 days Section 17 group, p<0·001) the number of patients readmitted did not differ between groups (59 [36%] of 166 patients in the CTO group vs 60 [36%] of 167 patients in the Section 17 group; adjusted relative risk 1·0 [95% CI 0·75-1·33]). INTERPRETATION: In well coordinated mental health services the imposition of compulsory supervision does not reduce the rate of readmission of psychotic patients. We found no support in terms of any reduction in overall hospital admission to justify the significant curtailment of patients' personal liberty. FUNDING: National Institute of Health Research.

The reliability, validity, and applicability of an English language version of the Mini-ICF-APP.

PURPOSE: This study aimed at establishing the validity and reliability of an English language version of the Mini-ICF-APP. METHODS: One hundred and five patients under the care of secondary mental health care services were assessed using the Mini-ICF-APP and several well-established measures of functioning and symptom severity. 47 (45 %) patients were interviewed on two occasions to ascertain test-retest reliability and 50 (48 %) were interviewed by two researchers simultaneously to determine the instrument's inter-rater reliability. Occupational and sick leave status were also recorded to assess construct validity. RESULTS: The Mini-ICF-APP was found to have substantial internal consistency (Chronbach's α 0.869-0.912) and all 13 items correlated highly with the total score. Analysis also showed that the Mini-ICF-APP had good test-retest (ICC 0.832) and inter-rater (ICC 0.886) reliability. No statistically significant association with length of sick leave was found, but the unemployed scored higher on the Mini ICF-APP than those in employment (mean 18.4, SD 9.1 vs. 9.4, SD 6.4, p < 0.001). The Mini-ICF-APP correlated highly with the other measures of illness severity and functioning considered in the study. CONCLUSIONS: The English version of the Mini-ICF-APP is a reliable and valid measure of disorders of capacity as defined by the International Classification of Functioning. Further work is necessary to establish whether the scale could be divided into sub scales which would allow the instrument to more sensitively measure an individual's specific impairments.

Pressures to adhere to treatment ('leverage') in English mental healthcare.

BACKGROUND: Coercion has usually been equated with legal detention. Non-statutory pressures to adhere to treatment, 'leverage', have been identified as widespread in US public mental healthcare. It is not clear if this is so outside the USA. AIMS: To measure rates of different non-statutory pressures in distinct clinical populations in England, to test their associations with patient characteristics and compare them with US rates. METHOD: Data were collected by a structured interview conducted by independent researchers supplemented by data extraction from case notes. RESULTS: We recruited a sample of 417 participants from four differing clinical populations. Lifetime experience of leverage was reported in 35% of the sample, 63% in substance misusers, 33% and 30% in the psychosis samples and 15% in the non-psychosis sample. Leverage was associated with repeated hospitalisations, substance misuse diagnosis and lower insight as measured by the Insight and Treatment Attitudes Questionnaire. Housing leverage was the most frequent form (24%). Levels were markedly lower than those reported in the USA. CONCLUSIONS: Non-statutory pressure to adhere to treatment (leverage) is common in English mental healthcare but has received little clinical or research attention. Urgent attention is needed to understand its variation and place in community practice.

Why do some voluntary patients feel coerced into hospitalisation? A mixed-methods study.

This study aimed to investigate factors linked to perceived coercion at admission and during treatment among voluntary inpatients. Quantitative and qualitative methods were used. Two hundred seventy patients were screened for perceived coercion at admission. Those who felt coerced into admission rated their perceived coercion during treatment a month after admission. Patient characteristics and experiences were tested as predictors of coercion. In-depth interviews on experiences leading to perceived coercion were conducted with 36 participants and analysed thematically. Thirty-four percent of patients felt coerced into admission and half of those still felt coerced a month later. No patient characteristics were associated with perceived coercion. Those whose satisfaction with treatment increased more markedly between baseline and a month later were less likely to feel coerced a month after admission. In the qualitative interviews three themes leading to perceived coercion were identified: viewing the hospital as ineffective and other treatments as more appropriate, not participating in the admission and treatment and not feeling respected. Involving patients in the decision-making and treating them with respect may reduce perceived coercion.

Predictors of clinical and social outcomes following involuntary hospital admission: a prospective observational study.

The Study aimed to assess clinical and social outcomes following involuntary admissions over 1 year and identify socio-demographic and clinical patient characteristics associated with more or less favourable outcomes. Seven hundred and seventy-eight involuntary patients admitted to one of 22 hospitals in England were assessed within the first week after admission and at 1 month, 3 month and 12 month follow-ups. Outcome criteria were symptom levels, global functioning, objective social outcomes, and subjective quality of life (SQOL). Baseline characteristics and patients' initial experience were tested as predictors. Symptom levels and global functioning improved moderately. Objective social outcomes showed a small, but statistically significant deterioration, and SQOL a small, but significant improvement at 1 year. In multivariable analyses, admission due to risk to oneself and receiving benefits predicted poorer symptom outcomes. Female gender and higher perceived coercion were associated with better objective social outcomes, whilst higher initial satisfaction with treatment predicted more positive SQOL at follow-ups. Over a 1-year period following involuntary hospital admission, patients on average showed only limited health and social gains. Different types of outcomes are associated with different predictor variables. Patients' initial experience of treatment, in the form of perceived coercion or satisfaction with treatment, has predictive value for up to a year following the admission.

Patients' views and readmissions 1 year after involuntary hospitalisation.

BACKGROUND: Little is known about the long-term outcome of involuntary admissions to psychiatric hospitals. AIMS: To assess involuntary readmissions and patients' retrospective views of the justification of the admission as 1-year outcomes and to identify factors associated with these outcomes. METHOD: Socio-demographic data and readmissions were collected for 1570 involuntarily admitted patients. Within the first week after admission 50% were interviewed, and of these 51% were re-interviewed after 1 year. RESULTS: At 1 year, 15% of patients had been readmitted involuntarily, and 40% considered their original admission justified. Lower initial treatment satisfaction, being on benefits, living with others and being of African and/or Caribbean origin were associated with higher involuntary readmission rates. Higher initial treatment satisfaction, poorer initial global functioning and living alone were linked with more positive retrospective views of the admission. CONCLUSIONS: Patients' views of treatment within the first week are a relevant indicator for the long-term prognosis of involuntarily admitted patients.

Intravenous immunoglobulin and rituximab versus placebo treatment of antibody-associated psychosis: study protocol of a randomised phase IIa double-blinded placebo-controlled trial (SINAPPS2).

BACKGROUND: Evidence is conflicting about a causal role of inflammation in psychosis and, specifically, regarding antibodies binding to neuronal membrane targets, especially N-methyl-D-aspartate receptors. NMDAR, LGI1 and GABA-A antibodies were found more prevalent in people with psychosis than in healthy controls. We aim to test whether these antibodies are pathogenic and may cause isolated psychosis. The SINAPPS2 phase IIa double-blinded randomised controlled trial will test the efficacy and safety of immunoglobulin and rituximab treatment versus placebo for patients with acute psychosis symptoms as added to psychiatric standard of care. METHODS: We will screen approximately 2500 adult patients with acute psychosis to identify 160 with antibody-positive psychosis without co-existing neurological disease and recruit about 80 eligible participants to the trial in the period from September 2017 to September 2021 across the UK. Eligible patients will be randomised 1:1 either to intravenous immunoglobulin (IVIG) followed by rituximab or to placebo infusions of 1% albumin followed by 0.9% sodium chloride, respectively. To detect a time-to-symptomatic-recovery hazard ratio of 0.322 with a power of 80%, 56 participants are needed to complete the trial, allowing for up to 12 participants to drop out of each group. Eligible patients will be randomised and assessed at baseline within 4 weeks of their eligibility confirmation. The treatment will start with IVIG or 1% albumin placebo infusions over 2-4 consecutive days no later than 7 days from baseline. It will continue 4-5 weeks later with a rituximab or sodium chloride placebo infusion and will end 2-3 weeks after this with another rituximab or placebo infusion. The primary outcome is the time to symptomatic recovery defined as symptomatic remission sustained for at least 6 months on the following Positive and Negative Syndrome Scale items: P1, P2, P3, N1, N4, N6, G5 and G9. Participants will be followed for 12 months from the first day of treatment or, where sustained remission begins after the first 6 months, for an additional minimum of 6 months to assess later response. DISCUSSION: The SINAPPS2 trial aims to test whether immunotherapy is efficacious and safe in psychosis associated with anti-neuronal membrane antibodies. TRIAL REGISTRATION: ISRCTN, 11177045. Registered on 2 May 2017. EudraCT, 2016-000118-31. Registered on 22 November 2016. ClinicalTrials.gov, NCT03194815. Registered on 21 June 2017.

Factorial structure and long-term stability of the Autonomy Preference Index.

The autonomy preference index scale (API) has been designed to measure patient preference for 2 dimensions of autonomy: Their desire to take part in making medical decisions (decision making, [DM]) and their desire to be informed about their illness and the treatment (information seeking; [IS]). The DM dimension is measured by 6 general items together with 9 items related to 3 clinical vignettes (3 × 3 items). The IS dimension is measured by 8 items. While the API is widely used, a review of literature has identified several inconsistencies in the way it is scored. The first aim of this study was to determine the best scoring structure of the API on the basis of validity and reliability evidence. The second aim was to investigate the long-term stability of API scores. Two-hundred and 85 patients with a diagnosis of psychosis were assessed as they were about to be discharged from involuntary psychiatric hospitalization and they were reassessed after 6 and 12 months. Confirmatory factor analysis (CFA) revealed that a 3-factor solution was most adequate and that 2 distinct DM subscales should be preferred to 1 total DM score. While internal consistency estimates of the 3 subscales were good, the long-term stability of API scores was only modest. Multigroup-CFA revealed scalar invariance indicating API scores kept the same meaning longitudinally. In conclusion, a 3-factor structure seemed to be most adequate for the API scale. Long-term stability estimates suggested that clinicians should regularly assess patients' preferences for autonomy because API scores fluctuate over time. (PsycINFO Database Record

Cost-Effectiveness of Financial Incentives to Promote Adherence to Depot Antipsychotic Medication: Economic Evaluation of a Cluster-Randomised Controlled Trial.

BACKGROUND: Offering a modest financial incentive to people with psychosis can promote adherence to depot antipsychotic medication, but the cost-effectiveness of this approach has not been examined. METHODS: Economic evaluation within a pragmatic cluster-randomised controlled trial. 141 patients under the care of 73 teams (clusters) were randomised to intervention or control; 138 patients with diagnoses of schizophrenia, schizo-affective disorder or bipolar disorder participated. Intervention participants received £15 per depot injection over 12 months, additional to usual acute, mental and community primary health services. The control group received usual health services. Main outcome measures: incremental cost per 20% increase in adherence to depot antipsychotic medication; incremental cost of 'good' adherence (defined as taking at least 95% of the prescribed number of depot medications over the intervention period). FINDINGS: Economic and outcome data for baseline and 12-month follow-up were available for 117 participants. The adjusted difference in adherence between groups was 12.2% (73.4% control vs. 85.6% intervention); the adjusted costs difference was £598 (95% CI -£4,533, £5,730). The extra cost per patient to increase adherence to depot medications by 20% was £982 (95% CI -£8,020, £14,000). The extra cost per patient of achieving 'good' adherence was £2,950 (CI -£19,400, £27,800). Probability of cost-effectiveness exceeded 97.5% at willingness-to-pay values of £14,000 for a 20% increase in adherence and £27,800 for good adherence. INTERPRETATION: Offering a modest financial incentive to people with psychosis is cost-effective in promoting adherence to depot antipsychotic medication. Direct healthcare costs (including costs of the financial incentive) are unlikely to be increased by this intervention. TRIAL REGISTRATION: ISRCTN.com 77769281.

Effect of increased compulsion on readmission to hospital or disengagement from community services for patients with psychosis: follow-up of a cohort from the OCTET trial.

BACKGROUND: Community treatment orders (CTOs) have not been shown in randomised trials to reduce readmission to hospital in patients with psychosis, but these trials have been short (11-12 months). We previously investigated the effect of CTOs on readmission rates over 12 months in a randomised trial (OCTET). Here, we present follow-up data for a cohort of individuals recruited to our original trial to examine the long-term effect of CTOs on readmissions and the risk of patients disengaging from mental health services temporarily or enduringly. METHODS: For OCTET, an open-label, parallel, randomised controlled trial, we recruited patients aged 18-65 years involuntarily admitted to mental health hospitals in 32 trusts in England, with a diagnosis of psychosis and deemed suitable for CTOs by their clinicians. Between Nov 10, 2008, and Feb 22, 2011, we recruited and randomly assigned 336 eligible patients (1:1) to be discharged on either a CTO (n=167) or to voluntary status via Section 17 leave (control group; n=169). For the analysis presented in this report, we assessed data at 36 months for 330 of these patients. We tested rates of readmission to hospital, time to first readmission, number of readmissions, and duration of readmission in patients assigned to CTO versus those assigned to control, and in all patients with CTO experience at any time in the 36 months versus those without. We also tested whether duration of CTO affected readmission outcomes in patients with CTO experience. We examined discontinuation (≥60 days between clinical contacts) and disengagement from services (no clinical contact for ≥90 days with no return to contact) in the whole cohort. OCTET is registered with isrctn.com, number ISRCTN73110773. FINDINGS: We obtained data for 330 patients in the relevant period between Nov 10, 2008 and Feb 22, 2014 (36 months after the last patient was randomly assigned to OCTET). We identified no difference between the randomised groups in the numbers of patients readmitted (100 [61%] of 165 CTOs vs 113 [68%] of 165 controls; relative risk 0·88 [95% CI 0·75-1·03]), number of readmissions (mean 2·4 readmissions [SD 1·91] vs 2·2 [1·43]; incident density ratio [IDR] 0·97 [95% CI 0·76-1·24]), duration of readmissions (median 117·5 days [IQR 63-303] vs 139·5 days [63·0-309·5]; IDR 0·84 [95% CI 0·51-1·38]), or time to first readmission (median 601·0 days [95% CI 387·0-777·0] vs 420·0 days [352·0-548·0]; hazard ratio [HR] 0·81 [95% CI 0·62-1·06]). The CTO experience group had significantly more readmissions than the group without (IDR 1·39 [95% CI 1·07-1·79]) and we noted no significant difference between groups in readmission rates, duration of readmission, or time to first readmission. We did not identify a linear relationship between readmission outcomes and duration of CTO. 19 (6%) patients disengaged from services (12 [7%] of 165 CTOs vs 7 [4%] of 165 controls). Longer duration of compulsion was associated with later disengagement (HR 0·946 [95% CI 0·90-0·99, p=0·023). 187 (57%) experienced no discontinuities, and we noted no significant difference between the CTO and control groups for time to disengagement or number of discontinuities. Levels of discontinuity were associated with compulsion (IDR 0·973 [95% CI 0·96-0·99, p<0·0001]. We identified no effect of baseline characteristics on the associations between compulsion and disengagement. INTERPRETATION: We identified no evidence that increased compulsion leads to improved readmission outcomes or to disengagement from services in patients with psychosis over 36 months. The level of persisting clinical follow-up was much higher than expected, irrespective of CTO status, and could partly account for the absence of CTO effect. The findings from our 36-month follow-up support our original findings that CTOs do not provide patient benefits, and the continued high level of their use should be reviewed. FUNDING: National Institute for Health Research.

Operationalising the capability approach for outcome measurement in mental health research.

Amartya Sen's multidimensional capability approach focuses on the importance of freedoms to be or do things people have reason to value. It is an alternative to standard utilitarian welfarism, the theoretical approach to quality-adjusted life years (QALYs) and cost-utility analyses. Despite the limitations of the utility approach in capturing non-health benefits and broader welfare inequalities, there have been very limited applications of the capability approach in the mental health context where these issues are imperative. We report the development and application of a multidimensional instrument, the OxCAP-MH, which aims to operationalise the capability approach for outcome measurement in mental health research. The study was carried out as part of an ongoing programme on community coercion experienced by service users with severe and enduring mental illness being treated using Community Treatment Orders. Capabilities data were collected at baseline in the OCTET RCT for 333 'revolving door' mental health service users who were in involuntary hospital treatment at the time of recruitment in England (2008-2011). The research focused on the identification of capabilities domains most affected by mental illness and their association with socio-demographic and clinical factors and other measures of well-being such as the EQ-5D and Global Assessment of Functioning (GAF) scales. The OxCAP-MH item response rate was 90%-68%. There were significant correlations between service users' overall capability scores and the GAF, EQ-5D VAS and EQ-5D-3L utilities (corr = 0.249, 0.514, 0.415, respectively). The most affected capability domains were: 'Daily activities', 'Influencing local decisions', 'Enjoying recreation', 'Planning one's life' and 'Discrimination'. Age had a mixed effect, while female service users and those with a primary diagnosis of schizophrenia or longer illness duration reported significantly lower capability scores. The results support the feasibility and validity of directly measuring human capabilities for the mentally ill and the potential for applying the approach to outcome measurement.

Effectiveness of financial incentives to improve adherence to maintenance treatment with antipsychotics: cluster randomised controlled trial.

OBJECTIVE: To test whether offering financial incentives to patients with psychotic disorders is effective in improving adherence to maintenance treatment with antipsychotics. DESIGN: Cluster randomised controlled trial. SETTING: Community mental health teams in secondary psychiatric care in the United Kingdom. PARTICIPANTS: Patients with a diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder, who were prescribed long acting antipsychotic (depot) injections but had received 75% or less of the prescribed injections. We randomly allocated 73 teams with a total of 141 patients. Primary outcome data were available for 35 intervention teams with 75 patients (96% of randomised) and for 31 control teams with 56 patients (89% of randomised). INTERVENTIONS: Participants in the intervention group were offered £15 (€17; $22) for each depot injection over a 12 month period. Participants in the control condition received treatment as usual. MAIN OUTCOME MEASURE: The primary outcome was the percentage of prescribed depot injections given during the 12 month intervention period. RESULTS: 73 teams with 141 consenting patients were randomised, and outcomes were assessed for 131 patients (93%). Average baseline adherence was 69% in the intervention group and 67% in the control group. During the 12 month trial period adherence was 85% in the intervention group and 71% in the control group. The adjusted effect estimate was 11.5% (95% confidence interval 3.9% to 19.0%, P=0.003). A secondary outcome was an adherence of ≥ 95%, which was achieved in 28% of the intervention group and 5% of the control group (adjusted odds ratio 8.21, 95% confidence interval 2.00 to 33.67, P=0.003). Although differences in clinician rated clinical improvement between the groups failed to reach statistical significance, patients in the intervention group had more favourable subjective quality of life ratings (ß=0.71, 95% confidence interval 0.26 to 1.15, P=0.002). The number of admissions to hospital and adverse events were low in both groups and did not show substantial differences. CONCLUSION: Offering modest financial incentives to patients with psychotic disorders is an effective method for improving adherence to maintenance treatment with antipsychotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77769281.

Family caregivers' experiences of involuntary psychiatric hospital admissions of their relatives--a qualitative study.

BACKGROUND: Family caregivers of people with mental disorders are frequently involved in involuntary hospital admissions of their relatives. OBJECTIVE: To explore family caregivers' experience of involuntary admission of their relative. METHOD: 30 in-depth interviews were conducted with family caregivers of 29 patients who had been involuntarily admitted to 12 hospitals across England. Interviews were analysed using thematic analysis. RESULTS: Four major themes of experiences were identified: relief and conflicting emotions in response to the relative's admission; frustration with a delay in getting help; being given the burden of care by services; and difficulties with confidentiality. Relief was a predominant emotion as a response to the relative's admission and it was accompanied by feelings of guilt and worry. Family caregivers frequently experienced difficulties in obtaining help from services prior to involuntary admission and some thought that services responded to crises rather than prevented them. Family caregivers experienced increased burden when services shifted the responsibility of caring for their mentally unwell relatives to them. Confidentiality was a delicate issue with family caregivers wanting more information and a say in decisions when they were responsible for aftercare, and being concerned about confidentiality of information they provided to services. CONCLUSION: Compulsory admission of a close relative can be a complex and stressful experience for family caregivers. In order for caregivers to be effective partners in care, a balance needs to be struck between valuing their involvement in providing care for a patient and not overburdening them.