The prevalence of personality disorders in the community: a global systematic review and meta-analysis.

BACKGROUND: Personality disorders are now internationally recognised as a mental health priority. Nevertheless, there are no systematic reviews examining the global prevalence of personality disorders. AIMS: To calculate the worldwide prevalence of personality disorders and examine whether rates vary between high-income countries and low- and middle-income countries (LMICs). METHOD: We systematically searched PsycINFO, MEDLINE, EMBASE and PubMed from January 1980 to May 2018 to identify articles reporting personality disorder prevalence rates in community populations (PROSPERO registration number: CRD42017065094). RESULTS: A total of 46 studies (from 21 different countries spanning 6 continents) satisfied inclusion criteria. The worldwide pooled prevalence of any personality disorder was 7.8% (95% CI 6.1-9.5). Rates were greater in high-income countries (9.6%, 95% CI 7.9-11.3%) compared with LMICs (4.3%, 95% CI 2.6-6.1%). In univariate meta-regressions, significant heterogeneity was partly attributable to study design (two-stage v. one-stage assessment), county income (high-income countries v. LMICs) and interview administration (clinician v. trained graduate). In multiple meta-regression analysis, study design remained a significant predictor of heterogeneity. Global rates of cluster A, B and C personality disorders were 3.8% (95% CI 3.2, 4.4%), 2.8% (1.6, 3.7%) and 5.0% (4.2, 5.9%). CONCLUSIONS: Personality disorders are prevalent globally. Nevertheless, pooled prevalence rates should be interpreted with caution due to high levels of heterogeneity. More large-scale studies with standardised methodologies are now needed to increase our understanding of population needs and regional variations.

Long-stay in forensic-psychiatric care in the UK.

PURPOSE: Forensic services provide care for mentally disordered offenders. In England this is provided at three levels of security-low, medium and high. Significant number of patients within these settings remain detained for protracted periods of time. This is both very costly and restrictive for individuals. No national studies have been conducted on this subject in England. METHODS: We employed a cross-sectional design using anonymised data from medical records departments in English secure forensic units. Data were collected from a large sample of medium secure patients (n = 1572) as well as the total high secure patient population (n = 715) resident on the census date (01-04-2013). We defined long-stay as a stay of more than 10 years in high, 5 years in medium or 15 years in a mix of high and medium secure settings. Long-stay status was assessed against patient demographic and admission information. RESULTS: We identified a significant proportion of long-stayers: 23.5% in high secure and 18.1% in medium secure care. Amongst medium secure units a large variation in long-stay prevalence was observed from 0 to 50%. Results indicated that MHA section, admission source and current ward type were independent factors associated with long-stay status. CONCLUSION: This study identified a significant proportion of long-stayers in forensic settings in England. Sociodemographic factors identified in studies in individual settings may be less important than previously thought. The large variation in prevalence of long-stayers observed in the medium secure sample warrants further investigation.

What influences social outcomes among offenders with personality disorder: A systematic review.

BACKGROUND: Personality disorder is highly prevalent in offender populations and is associated with poor health, criminal justice, and social outcomes. Research has been conducted into factors that influence offending and health, but, in order to improve (re)habilitation, service providers must also be able to identify the variables associated with social outcomes and the mechanisms by which they operate. AIM: To establish what is known about what influences social outcomes among offenders with personality disorder. METHOD: A systematic review was completed using Cochrane methods, expanded to include nonrandomised trials. Anticipated high heterogeneity informed a narrative synthesis. RESULTS: Three studies met inclusion criteria. Two were qualitative studies including only 13 cases between them. All studies were low quality. CONCLUSIONS: There is insufficient evidence to determine what influences good social outcomes among offenders with personality disorder. Research is required to identify associated variables, to inform the development of effective interventions.

How effective are interventions to improve social outcomes among offenders with personality disorder: a systematic review.

BACKGROUND: Offenders with personality disorder are supported by health, criminal justice, social care and third sector services. These services are tasked with reducing risk, improving health and improving social outcomes. Research has been conducted into interventions that reduce risk or improve health. However, interventions to improve social outcomes are less clearly defined. METHODS: To review the effectiveness of interventions to improve social outcomes we conducted a systematic review using Cochrane methodology, expanded to include non-randomised trials. Anticipated high heterogeneity of the studies informed narrative synthesis. RESULTS: Eleven studies met inclusion criteria. Five contained extractable data. No high-quality studies were identified. Outcomes measured clustered around employment and social functioning. Interventions vary and their mechanisms for influencing social outcomes are poorly operationalised. Although change was observed in employment rates, there was no evidence for the effectiveness of these interventions. CONCLUSIONS: There is a lack of evidence for effective interventions that improve social outcomes. Further research is recommended to reach consensus on the outcomes of importance, identify the factors that influence these and design theoretically-informed and evidence-based interventions.

Risperidone (depot) for schizophrenia.

BACKGROUND: Risperidone is the first new generation antipsychotic drug made available in a long-acting injection formulation. OBJECTIVES: To examine the effects of depot risperidone for treatment of schizophrenia or related psychoses in comparison with placebo, no treatment or other antipsychotic medication.To critically appraise and summarise current evidence on the resource use, cost and cost-effectiveness of risperidone (depot) for schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Register (December 2002, 2012, and October 28, 2015). We also checked the references of all included studies, and contacted industry and authors of included studies. SELECTION CRITERIA: Randomised clinical trials comparing depot risperidone with other treatments for people with schizophrenia and/or schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed trial quality and extracted data. For dichotomous data, we calculated the risk ratio (RR), with 95% confidence interval (CI). For continuous data, we calculated mean differences (MD). We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. MAIN RESULTS: Twelve studies, with a total of 5723 participants were randomised to the following comparison treatments: Risperidone depot versus placebo Outcomes of relapse and improvement in mental state were neither measured or reported. In terms of other primary outcomes, more people receiving placebo left the study early by 12 weeks (1 RCT, n=400, RR 0.74 95% CI 0.63 to 0.88, very low quality evidence), experienced severe adverse events in short term (1 RCT, n=400, RR 0.59 95% CI 0.38 to 0.93, very low quality evidence). There was however, no difference in levels of weight gain between groups (1 RCT, n=400, RR 2.11 95% CI 0.48 to 9.18, very low quality evidence). Risperidone depot versus general oral antipsychotics The outcome of improvement in mental state was not presented due to high levels of attrition, nor were levels of severe adverse events explicitly reported. Most primary outcomes of interest showed no difference between treatment groups. However, more people receiving depot risperidone experienced nervous system disorders (long-term:1 RCT, n=369, RR 1.34 95% CI 1.13 to 1.58, very-low quality evidence). Risperidone depot versus oral risperidoneData for relapse and severe adverse events were not reported. All outcomes of interest were rated as moderate quality evidence. Main results showed no differences between treatment groups with equivocal data for change in mental state, numbers leaving the study early, any extrapyramidal symptoms, weight increase and prolactin-related adverse events. Risperidone depot versus oral quetiapine Relapse rates and improvement in mental state were not reported. Fewer people receiving risperidone depot left the study early (long-term: 1 RCT, n=666, RR 0.84 95% CI 0.74 to 0.95, moderate quality evidence). Experience of serious adverse events was similar between groups (low quality evidence), but more people receiving depot risperidone experienced EPS (1 RCT, n=666, RR 1.83 95% CI 1.07 to 3.15, low quality evidence), had greater weight gain (1 RCT, n=666, RR 1.25 95% CI 0.25 to 2.25, low quality evidence) and more prolactin-related adverse events (1 RCT, n=666, RR 3.07 95% CI 1.13 to 8.36, very low quality evidence). Risperidone depot versus oral aripiprazoleRelapse rates, mental state using PANSS, leaving the study early, serious adverse events and weight increase were similar between groups. However more people receiving depot risperidone experienced prolactin-related adverse events compared to those receiving oral aripiprazole (2 RCTs, n=729, RR 9.91 95% CI 2.78 to 35.29, very low quality of evidence). Risperidone depot versus oral olanzapineRelapse rates were not reported in any of the included studies for this comparison. Improvement in mental state using PANSS and instances of severe adverse events were similar between groups. More people receiving depot risperidone left the study early than those receiving oral olanzapine (1 RCT, n=618, RR 1.32 95% CI 1.10 to 1.58, low quality evidence) with those receiving risperidone depot also experiencing more extrapyramidal symptoms (1 RCT, n=547, RR 1.67 95% CI 1.19 to 2.36, low quality evidence). However, more people receiving oral olanzapine experienced weight increase (1 RCT, n=547, RR 0.56 95% CI 0.42 to 0.75, low quality evidence). Risperidone depot versus atypical depot antipsychotics (specifically paliperidone palmitate)Relapse rates were not reported and rates of response using PANSS, weight increase, prolactin-related adverse events and glucose-related adverse events were similar between groups. Fewer people left the study early due to lack of efficacy from the risperidone depot group (long term: 1 RCT, n=749, RR 0.60 95% CI 0.45 to 0.81, low quality evidence), but more people receiving depot risperidone required use of EPS-medication (2 RCTs, n=1666, RR 1.46 95% CI 1.18 to 1.8, moderate quality evidence). Risperidone depot versus typical depot antipsychoticsOutcomes of relapse, severe adverse events or movement disorders were not reported. Outcomes relating to improvement in mental state demonstrated no difference between groups (low quality evidence). However, more people receiving depot risperidone compared to other typical depots left the study early (long-term:1 RCT, n=62, RR 3.05 95% CI 1.12 to 8.31, low quality evidence). AUTHORS' CONCLUSIONS: Depot risperidone may be more acceptable than placebo injection but it is hard to know if it is any more effective in controlling the symptoms of schizophrenia. The active drug, especially higher doses, may be associated with more movement disorders than placebo. People already stabilised on oral risperidone may continue to maintain benefit if treated with depot risperidone and avoid the need to take tablets, at least in the short term. In people who are happy to take oral medication the depot risperidone is approximately equal to oral risperidone. It is possible that the depot formulation, however, can bring a second-generation antipsychotic to people who do not reliably adhere to treatment. People with schizophrenia who have difficulty adhering to treatment, however, are unlikely to volunteer for a clinical trial. Such people may gain benefit from the depot risperidone with no increased risk of extrapyramidal side effects.

Fluphenazine (oral) versus atypical antipsychotics for schizophrenia.

BACKGROUND: Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. OBJECTIVES: To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. SEARCH METHODS: We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. DATA COLLECTION AND ANALYSIS: Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. MAIN RESULTS: Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes including relapse, changes in life skills, quality of life or cost-effectiveness.Comparing oral fluphenazine with risperidone, data showed no difference between groups for 'clinically important response' (1 RCT, n = 26, RR 0.67 95% CI 0.13 to 3.35, very low-quality evidence) nor leaving the study early due to inefficacy (1 RCT, n = 25, RR 1.08 95% CI 0.08 to 15.46, very low-quality evidence). No data were reported data for relapse; change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Once again there was no difference when oral fluphenazine was compared with quetiapine for clinically important response (1 RCT, n = 25, RR 0.62 95% CI 0.12 to 3.07, very low-quality evidence), nor leaving the study early for any reason (1 RCT, n = 25, RR 0.46 95% CI 0.05 to 4.46, very low-quality evidence). No data were reported for relapse; clinically important change in life skills; quality of life; extrapyramidal adverse effects; or cost-effectiveness.Compared to olanzapine, fluphenazine showed no superiority for clinically important response (1 RCT, n = 60, RR 1.33 95% CI 0.86 to 2.07, very low-quality evidence), in incidence of akathisia (1 RCT, n = 60, RR 3.00 95% CI 0.90 to 10.01, very low-quality evidence) or in people leaving the study early (1 RCT, n = 60, RR 3.00 95% CI 0.33 to 27.23, very low-quality evidence). No data were reported for relapse; change in life skills; quality of life; or cost-effectiveness. AUTHORS' CONCLUSIONS: Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride, risperidone, quetiapine or olanzapine. Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs. All included trials carry a substantial risk of bias regarding reporting of adverse effects and this bias would have favoured the newer drugs. The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics.

Trifluoperazine versus placebo for schizophrenia.

BACKGROUND: Trifluoperazine is a long-established high potency typical antipsychotic drug used in the treatment of schizophrenia and schizophrenia-like illnesses. OBJECTIVES: To determine absolute effects of trifluoperazine for schizophrenia and schizophrenia-like illnesses compared with placebo.To critically appraise and summarise current evidence on the resource use, cost and economic evaluation of trifluoperazine compared with placebo for schizophrenia. SEARCH METHODS: Searches of the Cochrane Schizophrenia Group's register of trials (July 2012), supplemented with handsearching, reference searching, personal communication and contact with industry. Two review authors undertook a search for economic studies using the Cochrane Schizophrenia Group's Health Economic Database (CSzGHED) on the 9th April 2013. SELECTION CRITERIA: All available clinical randomised trials involving people with schizophrenia and schizophrenia-like illnesses that compare trifluoperazine with placebo. DATA COLLECTION AND ANALYSIS: Studies for the effects of interventions were reliably selected by a review team and data were doubly independently extracted to reduce bias. We only used dichotomous data, using intention-to-treat analysis when possible. Data were estimated using risk ratio (RR) with 95% confidence intervals (CI). A 'Summary of findings' table was produced, where possible, for each primary outcome using GRADE. Economic studies were searched and reliably selected by review authors (VF and SS) to provide an economic summary of available data. Where no relevant economic studies were eligible for inclusion, the economic review team valued the already-included effectiveness outcome data to provide a rudimentary economic summary. MAIN RESULTS: This review included 10 studies with a total number of 686 participants featuring in 20 different outcomes of interest. Overall, there was significant clinical improvement in clinical global state at medium term amongst people receiving trifluoperazine (3 RCTs, n = 417, RR 4.61, CI 1.54 to 13.84, low quality evidence) and significantly fewer people receiving trifluoperazine left the studies early due to relapse or worsening at medium term (2 RCTs, n = 381, RR 0.34, CI 0.23 to 0.49, low quality evidence). However, results were equivocal for leaving the study early at medium term for any reason (2 RCTs, n = 391, RR 0.80, CI 0.17 to 3.81, very low quality evidence) and due to severe adverse effects (2 RCTs, n = 391, RR 1.54, CI 0.56 to 4.24, very low quality evidence). Equivocal data were also found for intensified symptoms at medium term (2 RCTs, n = 80, RR 1.05, CI 0.54 to 2.05, very low quality evidence) and rates of agitation or distress again at medium term (1 RCT, n = 52, RR 2.00, CI 0.19 to 20.72, very low quality evidence). Comparison between low and high-dose trifluoperazine with placebo from a single study provided equivocal evidence of effects. For economic outcomes, we valued outcomes in GBP terms and presented them in additional tables; there was an estimated saving of £3488.3 in favour of trifluoperazine. However, numerous assumptions were made and these savings need to be interpreted in light of those assumptions. AUTHORS' CONCLUSIONS: Our results agree with existing evidence that compared to placebo, trifluoperazine is an effective antipsychotic for people with schizophrenia. Furthermore, our review provides supportive evidence that trifluoperazine increases the risk of extrapyramidal adverse effects. Although the effect sizes against placebo are similar to those observed with other agents, they are based on data from many small, pre-CONSORT trials with generally either a low or very low GRADE evidence that has limited implication for clinical practice. Large, independent trials are needed that adhere to the CONSORT statement to compare trifluoperazine with placebo used in the treatment of schizophrenia and schizophrenia-like illnesses.

Development and validation of home-based psychosocial self-management interventions in schizophrenia and related disorders in low-resource settings: A mixed methods approach.

Background: Psychosocial interventions, crucial for recovery in patients with schizophrenia, have often been developed and tested in high income countries. We aimed at developing and validating home-based a booklet based psycho-social intervention with inputs from stakeholders: patients, families, and mental health professionals (MHP) for patients with schizophrenia and related disorders in low resource settings. Methods: We developed a preliminary version of psychosocial intervention booklets based on six themes derived from focus group discussions conducted with patients, families, and MHP. Initially, quantitative assessment of content validity was done by MHP on overall and Content Validity Index of individual items of the specific booklets, followed by in-depth interviews about their views. The booklets were modified based on their inputs. Further, pilot testing of manuals was done on the users - nine pairs of patients and caregivers followed by development of a final version of psycho-social intervention. Results: The percentage content validity of individual modules and overall booklets was ≥78.5% indicating good validity. Most MHP reported that the manuals were relevant and easy to use but were text-heavy, and lengthy. On pilot testing of modified manuals with patients and their family caregivers, majority (77.8%) of them found booklets useful and suggested that there should be separate booklets for both patients and caregivers for providing information and entering separate response for the activities, integrating helpful tips. Language should be simple. Finally, two sets of booklets ("info book" and "workbook") named 'Saksham' (meaning empowered) were created with specific modules (viz., 'Medicine adherence', 'Daily routine', 'Eating right', 'Physical activity', 'Physical health monitoring', 'Self-reliance', and 'Psychoeducation') for patients and caregivers each, in two languages (Hindi and English). Conclusion: Booklets with modules for psychosocial interventions for patients with schizophrenia and their caregivers were developed after establishing content validity and pilot testing.

Protocol-based assessment and management of first episode psychosis: Comparison of short and medium-term outcomes in psychopathology, quality of life, functioning and family burden across two sites in India.

BACKGROUND: Standard assessment and management protocols exist for first episode psychosis (FEP) in high income countries. Due to cultural and resource differences, these need to be modified for application in low-and middle-income countries. AIMS: To assess the applicability of standard assessment and management protocols across two cohorts of FEP patients in North and South India by examining trajectories of psychopathology, functioning, quality of life and family burden in both. METHOD: FEP patients at two sites (108 at AIIMS, North India, and 115 at SCARF, South India) were assessed using structured instruments at baseline, 3, 6 and 12 months. Standard management protocols consisted of treatment with antipsychotics and psychoeducation for patients and their families. Generalised estimating equation (GEE) modelling was carried out to test for changes in outcomes both across and between sites at follow-up. RESULTS: There was an overall significant improvement in both cohorts for psychopathology and other outcome measures. The trajectories of improvement differed between the two sites with steeper improvement in non-affective psychosis in the first three months at SCARF, and affective symptoms in the first three months at AIIMS. The reduction in family burden and improvement in quality of life were greater at AIIMS than at SCARF during the first three months. CONCLUSIONS: Despite variations in cultural contexts and norms, it is possible to implement FEP standard assessment and management protocols in North and South India. Preliminary findings indicate that FEP services lead to significant improvements in psychopathology, functioning, quality of life, and family burden within these contexts.

Designing and implementing a physical exercise intervention for people with first episode psychosis using experience-based co-design: A pilot study from Chennai, India.

BACKGROUND: Physical exercise can improve outcomes for people with first-episode psychosis (FEP). Co-designing physical exercise interventions with end users has the potential to enhance their acceptability, feasibility, and long-term viability. This study's objective was to use experience-based co-design (EBCD) methodology to develop a physical exercise intervention for FEP, and pilot test it. METHODS: The study was conducted at the Schizophrenia Research Foundation's FEP program in Chennai, India. Participants(N=36) were individuals with FEP and their caregivers, mental health professionals (MHPs, and physical training experts. EBCD methodology included one-to-one interviews, focus group discussions, joint conferences, and co-design workshops. Two instructional videos were developed. Twelve FEP patients engaged in physical exercise with help of the videos over three months. They were followed up through weekly phone calls and in-person interviews to capture data on regularity, frequency, location of exercise, and comfort levels. RESULTS: Several touch points emerged from the interviews, focus groups, and joint meetings including lack of motivation, knowledge about physical exercise; differing perspectives about physical exercise; limited resource, and time constraints. Two instructional videos demonstrating activities for participants incorporated strategies that addressed these touch points. Pilot data indicated that participants engaged with the physical exercise intervention over 3 months. CONCLUSION: This was the first study to use co-design methodology to design a physical exercise intervention for first-episode psychosis. The intervention may have therefore been responsive to stakeholder needs and preferences. Results of this study highlight the potential of co-design in designing and adapting interventions. There is need for rigorous testing with larger samples.

Effectiveness of a mental health literacy module on stigma related mental health knowledge and behaviour among youth in two educational settings in Chennai, South India: A quasi-experimental study.

BACKGROUND: Improving mental health literacy (MHL) can reduce stigma towards mental illness, decreasing delays in help-seeking for mental disorders such as psychosis. We aimed to develop and assess the impact of an interactive MHL intervention on stigma related mental health knowledge and behaviour (SRMHKB) among youth in two urban colleges in South India. METHODS: Incorporating input from stakeholders (students, teachers, and mental health professionals), we developed a mental health literacy module to address SRMHKB. The module was delivered as an interactive session lasting 90 min. We recruited 600 (300 males; 300 females; mean age 19.6) participants from two city colleges in Chennai from Jan-Dec 2019 to test the MHL module. We assessed SRMHKB before the delivery of the MHL intervention, immediately after, and at 3 and 6 months after the intervention using the Mental Health Knowledge Schedule (MAKS) and Reported and Intended Behaviour Scale (RIBS). We used generalised estimating equations (GEE) to assess the impact of the intervention over time. RESULTS: Compared to baseline, there was a statistically significant increase in stigma related knowledge and behaviour immediately after the intervention (coefficient=3.8; 95% CI: 3.5,4.1) and during the 3-month (coefficient=3.4; 95% CI: 3.0,3.7) and 6-month (coefficient=2.4; 95% CI: 2.0,2.7) follow-up. CONCLUSION: Preliminary findings suggest that a single 90-minute MHL interactive session could lead to improvements in SRMHKB among youth in India. Future research might utilise randomised controlled trials to corroborate findings, and explore how improvements can be sustained over the longer-term.

Atypical antipsychotics for psychosis in adolescents.

BACKGROUND: Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis. OBJECTIVES: To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases. DATA COLLECTION AND ANALYSIS: Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of bias was assessed for included studies. MAIN RESULTS: We included 13 RCTs, with a total of 1112 participants. We found no data on service utilisation, economic outcomes, behaviour or cognitive response. Trials were classified into the following groups. 1. Atypical antipsychotics versus placebo: Only two studies compared one atypical antipsychotic medication with placebo. In one study, the number of non-responders treated with olanzapine was not different from the number treated with placebo (1 RCT, n = 107, RR 0.84, 95% CI 0.65 to 1.10); however, significantly more (57% vs 32%) people left the study early (1 RCT, n = 107, RR 0.56, 95% CI 0.36 to 0.87) from the placebo group compared with the olanzapine group. With regard to adverse effects, young people treated with aripiprazole had significantly lower serum cholesterol compared with those given placebo (1 RCT, n = 302, RR 3.77, 95% CI 1.88 to 7.58). 2. Atypical antipsychotics versus typical antipsychotics: When the findings of all five trials comparing atypical antipsychotic medications with a typical antipsychotic medication were collated, no difference in the mean end point Brief Psychiatric Rating Scale (BPRS) score was noted between the two arms (5 RCTs, n = 236, MD -1.08, 95% CI -3.08 to 0.93). With regard to adverse effects, the mean end point serum prolactin concentration was much higher than the reference range for treatment with risperidone, olanzapine and molindone in one of the studies. However, fewer adolescents who were receiving atypical antipsychotic medications left the study because of adverse effects (3 RCTs, n = 187, RR 0.65, 95% CI 0.36 to 1.15) or for any reason (3 RCTs, n = 187, RR 0.62, 95% CI 0.39 to 0.97).3. One atypical antipsychotic versus another atypical antipsychotic: The mean end point BPRS score was not significantly different for people who received risperidone compared with those who received olanzapine; however, the above data were highly skewed. Overall no difference was noted in the number of people leaving the studies early because of any adverse effects between each study arm in the three studies comparing olanzapine and risperidone (3 RCTs, n = 130, RR 1.15, 95% CI 0.44 to 3.04). Specific adverse events were not reported uniformly across the six different studies included in this section of the review; therefore it was difficult to do a head-to-head comparison of adverse events for different atypical antipsychotic medications.4. Lower-dose atypical antipsychotic versus standard/higher-dose atypical antipsychotic: Three studies reported comparisons of lower doses of the atypical antipsychotic medication with standard/higher doses of the same medication. One study reported better symptom reduction with a standard dose of risperidone as compared with a low dose (1 RCT, n = 257, RR -8.00, 95% CI -13.75 to -2.25). In another study, no difference was reported in the number of participants not achieving remission between the group receiving 10 mg/d and those who received 30 mg/d of aripiprazole (1 RCT, n = 196, RR 0.84, 95% CI 0.48 to 1.48). Similarly in the other study, authors reported no statistically significant difference in clinical response between the two groups receiving lower-dose (80 mg/d) and higher-dose (160 mg/d) ziprasidone, as reflected by the mean end point BPRS score (1 RCT, n = 17, MD -4.40, 95% CI -19.20 to 10.40). AUTHORS' CONCLUSIONS: No convincing evidence suggests that atypical antipsychotic medications are superior to typical medications for the treatment of adolescents with psychosis. However, atypical antipsychotic medications may be more acceptable to young people because fewer symptomatic adverse effects are seen in the short term. Little evidence is available to support the superiority of one atypical antipsychotic medication over another, but side effect profiles are different for different medications. Treatment with olanzapine, risperidone and clozapine is often associated with weight gain. Aripiprazole is not associated with increased prolactin or with dyslipidaemia. Adolescents may respond better to standard-dose as opposed to lower-dose risperidone, but for aripiprazole and ziprasidone, lower doses may be equally effective. Future trials should ensure uniform ways of reporting.

Pathways to care in first-episode psychosis in low-resource settings: Implications for policy and practice.

OBJECTIVE: Developing countries such as India face a major mental health care gap. Delayed or inadequate care can have a profound impact on treatment outcomes. We compared pathways to care in first episode psychosis (FEP) between North and South India to inform solutions to bridge the treatment gap. METHODS: Cross-sectional observation study of 'untreated' FEP patients (n = 177) visiting a psychiatry department in two sites in India (AIIMS, New Delhi and SCARF, Chennai). We compared duration of untreated psychosis (DUP), first service encounters, illness attributions and socio-demographic factors between patients from North and South India. Correlates of DUP were explored using logistic regression analysis (DUP ≥ 6 months) and generalised linear models (DUP in weeks). RESULTS: Patients in North India had experienced longer DUP than patients in South India (ß = 17.68, p < 0.05). The most common first encounter in North India was with a faith healer (45.7%), however, this contact was not significantly associated with longer DUP. Visiting a faith healer was the second most common first contact in South India (23.6%) and was significantly associated with longer DUP (Odds Ratio: 6.84; 95% Confidence Interval: 1.77, 26.49). Being in paid employment was significantly associated with shorter DUP across both sites. CONCLUSIONS: Implementing early intervention strategies in a diverse country like India requires careful attention to local population demographics; one size may not fit all. A collaborative relationship between faith healers and mental health professionals could help with educational initiatives and to provide more accessible care.

Managing mental health crises in dental practice.

This paper aims to summarise current evidence and practice relating to mental health crises within dental practice. We review cases occurring within our practice, including management and lessons learnt. We then aim to provide a practical guide to manage such crises.

Developing an Intervention to Improve Occupational Participation for Justice-Involved People with a Personality Disorder: Defining and Describing Intervention Components.

Occupational participation is undertaking personally meaningful and socially valued activities and roles. It is an important outcome for health and justice interventions, as it is integral to health and desistance. We report the third of a four-stage research project to develop an intervention to improve occupational participation for justice-involved people with a personality disorder in the community. We completed a Delphi survey to produce expert consensus on intervention components and their content, ascertain participant ratings of 28 factors for their level of influence on occupational participation, and the modifiability of the factors with this population. Thirty multi-disciplinary participants completed three survey rounds. Most factors were rated very influential, but few were considered easily modifiable. Participants agreed 121 statements describing intervention components and content. Twenty-seven statements did not reach consensus. In targeting specific factors in intervention, practitioners must balance their degree of influence with potential modifiability. The results will inform intervention manualization and modeling.

Warwick-India-Canada (WIC) global mental health group: rationale, design and protocol.

INTRODUCTION: The primary aim of the National Institute of Health Research-funded global health research group, Warwick-India-Canada (WIC), is to reduce the burden of psychotic disorders in India. India has a large pool of undetected and untreated patients with psychosis and a treatment gap exceeding 75%. Evidence-based packages of care have been piloted, but delivery of treatments still remains a challenge. Even when patients access treatment, there is minimal to no continuity of care. The overarching ambition of WIC programme is to improve patient outcomes through (1) developing culturally tailored clinical interventions, (2) early identification and timely treatment of individuals with mental illness and (3) improving access to care by exploiting the potential of digital technologies. METHODS AND ANALYSIS: This multicentre, multicomponent research programme, comprising five work packages and two cross-cutting themes, is being conducted at two sites in India: Schizophrenia Research Foundation, Chennai (South India) and All India Institute of Medical Sciences, New Delhi (North India). WIC will (1) develop and evaluate evidence-informed interventions for early and first-episode psychosis; (2) determine pathways of care for early psychosis; (3) investigate the efficacy and cost-effectiveness of community care models, including digital and mobile technologies; (4) develop strategies to reduce the burden of mental illnesses among youth; (5) assess the economic burden of psychosis on patients and their carers; and (6) determine the feasibility of an early intervention in psychosis programme in India. ETHICS AND DISSEMINATION: This study was approved by the University of Warwick's Biomedical and Scientific Research Ethics Committee (reference: REGO-2018-2208), Coventry, UK and research ethics committees of all participating organisations. Research findings will be disseminated through peer-reviewed scientific publications, presentations at learnt societies and visual media.

Corrigendum: The Forensic Restrictiveness Questionnaire: Development, Validation, and Revision.

[This corrects the article DOI: 10.3389/fpsyt.2019.00805.].

Perceptions of Restrictiveness in Forensic Mental Health: Do Demographic, Clinical, and Legal Characteristics Matter?

Where safe, forensic mental health systems should provide care in the least restrictive environment possible. Doing so can maximize patient autonomy and empowerment while minimizing unnecessary social disconnection and stigmatization. This study investigated whether patients' perceptions of restrictiveness were associated with demographic, clinical, and legal characteristics. The Forensic Restrictiveness Questionnaire (FRQ) was used to measure perceptions of restrictiveness in 235 patients in low-, medium-, and high-secure settings in England. The results showed that restrictiveness scores were significantly higher for patients who experienced an adverse event in the past week or were diagnosed with a personality disorder compared to those with a mental illness. A regression analysis suggested that only diagnosis was predictive of FRQ scores when controlling for perceptions of ward atmosphere and quality of life. Age, length of stay, ethnicity, level of security, legal section, and offence type were not associated with FRQ scores. Future research should investigate the roles that individual symptoms, insight into illness, mood, personality, and expectations of care have in influencing perceptions of restrictiveness.

Functional role for the conformationally mobile phenylalanine 223 in the reaction of methylenetetrahydrofolate reductase from Escherichia coli.

The flavoprotein methylenetetrahydrofolate reductase from Escherichia coli catalyzes the reduction of 5,10-methylenetetrahydrofolate (CH(2)-H(4)folate) by NADH via a ping-pong reaction mechanism. Structures of the reduced enzyme in complex with NADH and of the oxidized Glu28Gln enzyme in complex with CH(3)-H(4)folate [Pejchal, R., Sargeant, R., and Ludwig, M. L. (2005) Biochemistry 44, 11447-11457] have revealed Phe223 as a conformationally mobile active site residue. In the NADH complex, the NADH adopts an unusual hairpin conformation and is wedged between the isoalloxazine ring of the FAD and the side chain of Phe223. In the folate complex, Phe223 swings out from its position in the NADH complex to stack against the p-aminobenzoate ring of the folate. Although Phe223 contacts each substrate in E. coli MTHFR, this residue is not invariant; for example, a leucine occurs at this site in the human enzyme. To examine the role of Phe223 in substrate binding and catalysis, we have constructed mutants Phe223Ala and Phe223Leu. As predicted, our results indicate that Phe223 participates in the binding of both substrates. The Phe223Ala mutation impairs NADH and CH(2)-H(4)folate binding each 40-fold yet slows catalysis of both half-reactions less than 2-fold. Affinity for CH(2)-H(4)folate is unaffected by the Phe223Leu mutation, and the variant catalyzes the oxidative half-reaction 3-fold faster than the wild-type enzyme. Structures of ligand-free Phe223Leu and Phe223Leu/Glu28Gln MTHFR in complex with CH(3)-H(4)folate have been determined at 1.65 and 1.70 A resolution, respectively. The structures show that the folate is bound in a catalytically competent conformation, and Leu223 undergoes a conformational change similar to that observed for Phe223 in the Glu28Gln-CH(3)-H(4)folate structure. Taken together, our results suggest that Leu may be a suitable replacement for Phe223 in the oxidative half-reaction of E. coli MTHFR.

The Forensic Restrictiveness Questionnaire: Development, Validation, and Revision.

Introduction: Forensic psychiatric care is often practiced in closed institutions. These highly regulated, secure, and prescriptive environments arguably reduce patient autonomy, self-expression, and personhood. Taken together these settings are restrictive as patients' active participation in clinical, organizational, community, and personal life-worlds are curtailed. The consequences of patients' experiences of restrictiveness have not been explored empirically. This study aimed to develop a psychometrically-valid measure of experiences of restrictiveness. This paper presents the development, validation, and revision of the Forensic Restrictiveness Questionnaire (FRQ). Methods: In total, 235 patients recruited from low, medium, and high secure hospitals across England completed the FRQ. The dimensionality of the 56-item FRQ was tested using Principle Axis Factor Analysis and parallel analysis. Internal consistency was explored with Cronbach's α. Ward climate (EssenCES) and quality of life (FQL-SV) questionnaires were completed by participants as indicators of convergent validity. Exploratory Factor Analysis (EFA) and Cronbach's α guided the removal of items that did not scale adequately. Results: The analysis indicated good psychometric properties. EFA revealed a unidimensional structure, suggesting a single latent factor. Convergent validity was confirmed as the FRQ was significantly negatively correlated with quality of life (Spearman's ρ = -0.72) and ward climate (Spearman's ρ = -0.61). Internal consistency was strong (α = 0.93). Forty-one items were removed from the pilot FRQ. The data indicate that a final 15-item FRQ is a valid and internally reliable measure. Conclusion: The FRQ offers a novel and helpful method for clinicians and researchers to measure and explore forensic patients' experiences of restrictiveness within secure hospitals.