The clinical effectiveness and cost effectiveness of clozapine for inpatients with severe borderline personality disorder (CALMED study): a randomised placebo-controlled trial.

Background: Data from case series suggest that clozapine may benefit inpatients with borderline personality disorder (BPD), but randomised trials have not been conducted. Methods: Multicentre, double-blind, placebo-controlled trial. We aimed to recruit 222 inpatients with severe BPD aged 18 or over, who had failed to respond to other antipsychotic medications. We randomly allocated participants on a 1:1 ratio to receive up to 400 mg of clozapine per day or an inert placebo using a remote web-based randomisation service. The primary outcome was total score on the Zanarini Rating scale for Borderline Personality Disorder (ZAN-BPD) at 6 months. Secondary outcomes included self-harm, aggression, resource use and costs, side effects and adverse events. We used a modified intention to treat analysis (mITT) restricted to those who took one or more dose of trial medication, using a general linear model fitted at 6 months adjusted for baseline score, allocation group and site. Results: The study closed early due to poor recruitment and the impact of the COVID-19 pandemic. Of 29 study participants, 24 (83%) were followed up at 6 months, of whom 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) participants assigned to clozapine and 6 (43%) of those assigned to placebo were still taking trial medication. Adjusted difference in mean total ZAN-BPD score at 6 months was -3.86 (95% Confidence Intervals = -10.04 to 2.32). There were 14 serious adverse events; 6 in the clozapine arm and 8 in the placebo arm of the trial. There was little difference in the cost of care between groups. Interpretation: We recruited insufficient participants to test the primary hypothesis. The study findings highlight problems in conducting placebo-controlled trials of clozapine and in using clozapine for people with BPD, outside specialist inpatient mental health units. Trial registration: ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.

Patient experience of lasting negative effects of psychological interventions for anxiety and depression in secondary mental health care services: a national cross-sectional study.

BACKGROUND: Patients who undergo psychological treatment can report both negative and positive effects, but evidence of factors influencing the likelihood of negative effects is limited. AIMS: To identify aspects of the organisation and delivery of secondary care psychological treatment services that are associated with patient experiences of negative effects. METHOD: Cross-sectional survey of people with anxiety and depression who ended psychological treatment delivered by 50 NHS trusts in England. Respondents were asked about how their treatment was organised and delivered and whether they experienced lasting negative effects. RESULTS: Of 662 respondents, 90 (14.1%) reported experiencing lasting negative effects. People over the age of 65 were less likely than younger respondents to report negative effects. There was an association between reporting neutral or negative effects and not being referred at what respondents considered to be the right time (OR = 1.712, 95% CI = 1.078-2.726), not receiving the right number of sessions (OR = 3.105, 95% CI = 1.934-4.987), and not discussing progress with their therapist (OR 2.063, 95% CI = 1.290-3.301). CONCLUSIONS: One in seven patients who took part in this survey reported lasting negative effects from psychological treatment. Steps should be taken to prepare people for the potential for negative experiences of treatment, and progress reviewed during therapy in an effort to identify and prevent negative effects.

Factors associated with shorter length of admission among people with dementia in England and Wales: retrospective cohort study.

OBJECTIVES: To identify aspects of the organisation and delivery of acute inpatient services for people with dementia that are associated with shorter length of hospital stay. DESIGN AND SETTING: Retrospective cohort study of patients admitted to 200 general hospitals in England and Wales. PARTICIPANTS: 10 106 people with dementia who took part in the third round of National Audit of Dementia. MAIN OUTCOME MEASURE: Length of admission to hospital. RESULTS: The median length of stay was 12 days (IQR=6-23 days). People with dementia spent less time in hospital when discharge planning was initiated within 24 hours of admission (estimated effect -0.24, 95% CI: -0.29 to -0.18, p<0.001). People from ethnic minorities had shorter length of stay (difference -0.066, 95% CI: -0.13 to -0.002, p=0.043). Patients with documented evidence of discussions having taken place between their carers and medical staff spent longer in hospital (difference 0.26, 95% CI: 0.21 to 0.32, p<0.001). These associations held true in a subsample of 669 patients admitted with hip fracture and data from 74 hospitals with above average carer-rated quality of care. CONCLUSIONS: The way that services for inpatients with dementia are delivered can influence how long they spend in hospital. Initiating discharge planning within the first 24 hours of admission may help reduce the amount of time that people with dementia spend in hospital.

Influence of apparently negative personality characteristics on the long-term outcome of health anxiety: Secondary analysis of a randomized controlled trial.

BACKGROUND: It is known that personality has an influence on the outcome of mental state disorders, but detailed studies on its long-term impact are few. We examined the influence of personality status on the 8-year outcome of health anxiety and its relationship to the effects of cognitive behaviour therapy in a randomized controlled trial. AIMS: This study aims to examine both the usefulness of the diagnosis of personality disorder and an additional measure of pathological dependence, in predicting the outcome of medical patients with health anxiety treated with cognitive behaviour therapy. Because the influence of personality is often shown in the long term, these assessments covered the period of 8 years after randomization. An additional aim is to examine the costs of different levels of personality dysfunction in each treatment group. METHOD: Personality dysfunction, using both ICD-10 and ICD-11 classifications of severity, was assessed at baseline by interview in a randomized controlled trial. Patients were also assessed for pathological dependence using the Dependent Personality Questionnaire, also scored along a severity dimension. Four hundred forty-four patients from medical clinics with pathological health anxiety were treated with a modified form of cognitive behaviour therapy for health anxiety (CBT-HA) or standard care. Total costs over follow-up were calculated from hospital data and compared by personality group. RESULTS: At baseline, 381 (86%) had some personality dysfunction, mainly at the lower level of personality difficulty (not formally a disorder). One hundred eighty four (41%) had a personality disorder. A similar proportion was found with regard to dependent personality. Using the ICD-10 classification, 153 patients (34.6%) had a personality disorder, with 83 (54.2%) having anxious or dependent personality disorder, 20 (13.1%) having an anankastic disorder, but also with 66 (43.1%) having mixed disorder. During initial treatment, those with personality disorder adhered more closely to CBT-HA, and after 8 years, they had a significantly better outcome than those with personality difficulty and no personality disorder (p < 0.002). Similar results were found in those scoring high on the Dependent Personality Questionnaire. All these differences increased over the follow-up period. Costs were similar in all groups but were somewhat higher in the CBT-HA one; this finding is hypothesised to be due to fuller hospital treatment once health anxiety is discounted. CONCLUSION: Personality disorder in people with health anxiety, particularly in those who have anxious and dependent traits, reinforces the benefits of cognitive behaviour therapy, particularly in the longer term. © 2020 The Authors Personality and Mental Health Published by John Wiley & Sons Ltd.

Structured Psychological Support for people with personality disorder: feasibility randomised controlled trial of a low-intensity intervention.

BACKGROUND: National guidance cautions against low-intensity interventions for people with personality disorder, but evidence from trials is lacking. AIMS: To test the feasibility of conducting a randomised trial of a low-intensity intervention for people with personality disorder. METHOD: Single-blind, feasibility trial (trial registration: ISRCTN14994755). We recruited people aged 18 or over with a clinical diagnosis of personality disorder from mental health services, excluding those with a coexisting organic or psychotic mental disorder. We randomly allocated participants via a remote system on a 1:1 ratio to six to ten sessions of Structured Psychological Support (SPS) or to treatment as usual. We assessed social functioning, mental health, health-related quality of life, satisfaction with care and resource use and costs at baseline and 24 weeks after randomisation. RESULTS: A total of 63 participants were randomly assigned to either SPS (n = 33) or treatment as usual (n = 30). Twenty-nine (88%) of those in the active arm of the trial received one or more session (median 7). Among 46 (73%) who were followed up at 24 weeks, social dysfunction was lower (-6.3, 95% CI -12.0 to -0.6, P = 0.03) and satisfaction with care was higher (6.5, 95% CI 2.5 to 10.4; P = 0.002) in those allocated to SPS. Statistically significant differences were not found in other outcomes. The cost of the intervention was low and total costs over 24 weeks were similar in both groups. CONCLUSIONS: SPS may provide an effective low-intensity intervention for people with personality disorder and should be tested in fully powered clinical trials.

Factors influencing use of community treatment orders and quality of care that people receive: results of a national survey in England and Wales.

Aims and methodWe conducted a secondary analysis of data from the National Audit of Psychosis to identify factors associated with use of community treatment orders (CTOs) and assess the quality of care that people on CTOs receive. RESULTS: Between 1.1 and 20.2% of patients in each trust were being treated on a CTO. Male gender, younger age, greater use of in-patient services, coexisting substance misuse and problems with cognition predicted use of CTOs. Patients on CTOs were more likely to be screened for physical health, have a current care plan, be given contact details for crisis support, and be offered cognitive-behavioural therapy.Clinical implicationsCTOs appear to be used as a framework for delivering higher-quality care to people with more complex needs. High levels of variation in the use of CTOs indicate a need for better evidence about the effects of this approach to patient care.Declaration of interestNone.

Improved mental health among LABILE study participants: A qualitative exploration.

Results of the LABILE trial showed no difference between people with BPD who were prescribed lamotrigine and those on placebo. However, most study participants experienced sustained improvement in their mental health during the trial. We conducted a thematic analysis of qualitative data from interviews with 47 LABILE study participants to identify factors that may have contributed to this improvement. We identified three main themes: initial reasons and expectations regarding trial participation, patients' experiences of the trial and areas of change. Reasons for participating in the trial included a search for consistent and stable professional care as well as altruistic motives. Improvements in symptoms over the course of the trial were explained by several factors including consistency provided by the research team, salience of the social context and the availability of alternative support networks. While participants appreciated the autonomy provided by the voluntary nature of the trial, they felt that improvements stemmed from the 'structure' brought about by their actively engaging in the study. This study highlights the importance of clear and transparent communication when treating people with BPD. Mental health professionals should ensure that services for people with BPD are consistent and structured. © 2019 John Wiley & Sons, Ltd.

Psychological Support for Personality (PSP) versus treatment as usual: study protocol for a feasibility randomized controlled trial of a low intensity intervention for people with personality disorder.

BACKGROUND: Previous research has demonstrated the clinical effectiveness of long-term psychological treatment for people with some types of personality disorder. However, the high intensity and cost of these interventions limit their availability. Lower-intensity interventions are increasingly being offered to people with personality disorder, but their clinical and cost effectiveness have not been properly tested in experimental studies. We therefore set out to develop a low intensity intervention for people with personality disorder and to test the feasibility of conducting a randomized controlled trial to compare the clinical effectiveness of this intervention with that of treatment as usual (TAU). METHODS: A two-arm, parallel-group, single-blind, randomized controlled trial of Psychological Support for Personality (PSP) versus TAU for people aged over 18 years, who are using secondary care mental health services and have personality disorder. We will exclude people with co-existing organic or psychotic mental disorders (dementia, bipolar affective disorder, delusional disorder, schizophrenia, schizoaffective disorder, or schizotypal disorder), those with cognitive or language difficulties that would preclude them from providing informed consent or compromise participation in study procedures, and those who are already receiving psychological treatment for personality disorder. Participants will be randomized via a remote system in a ratio of PSP to TAU of 1:1. Randomization will be stratified according to the referring team and gender of the participant. A single follow-up assessment will be conducted by masked researchers 24 weeks after randomization to assess mental health (using the Warwick and Edinburgh Well-Being Schedule), social functioning (using the Work and Social Adjustment Scale), health-related quality of life (EQ-5D-5 L), incidence of suicidal behavior, satisfaction with care (Client Satisfaction Questionnaire), and resource use and costs using a modified version of the Adult Service Use Schedule. In addition to this, each participant will be asked to complete the patient version of the Clinical Global Impression Scale. Feasibility and acceptability will primarily be judged by study recruitment rate and engagement and retention in treatment. The analysis will focus principally on descriptive data on the rate of recruitment, characteristics of participants, attrition, adherence to therapy, and follow-up. We will explore the distribution of study outcomes to investigate assumptions of normality in order to plan the analysis and sample size of a future definitive trial. DISCUSSION: Most people with personality disorder do not currently receive evidence-based interventions. While a number of high intensity psychological treatments have been shown to be effective, there is an urgent need to develop effective low intensity approaches to help people unable to use existing treatments. PSP is a low intensity intervention for individuals, which was developed following extensive consultation with users and providers of services for people with personality disorder. This study aims to examine the feasibility of a randomized trial of PSP compared to TAU for people with personality disorder. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN14994755 . Registered on 18 July 2017.

The Clinical Effectiveness and Cost-Effectiveness of Lamotrigine in Borderline Personality Disorder: A Randomized Placebo-Controlled Trial.

OBJECTIVE: The authors examined whether lamotrigine is a clinically effective and cost-effective treatment for people with borderline personality disorder. METHOD: This was a multicenter, double-blind, placebo-controlled randomized trial. Between July 2013 and November 2016, the authors recruited 276 people age 18 or over who met diagnostic criteria for borderline personality disorder. Individuals with coexisting bipolar affective disorder or psychosis, those already taking a mood stabilizer, and women at risk of pregnancy were excluded. A web-based randomization service was used to allocate participants randomly in a 1:1 ratio to receive either an inert placebo or up to 400 mg/day of lamotrigine. The primary outcome measure was score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. Secondary outcome measures included depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, and adverse events. RESULTS: A total of 195 (70.6%) participants were followed up at 52 weeks, at which point 49 (36%) of those in the lamotrigine group and 58 (42%) of those in the placebo group were taking study medication. The mean ZAN-BPD score was 11.3 (SD=6.6) among those in the lamotrigine group and 11.5 (SD=7.7) among those in the placebo group (adjusted difference in means=0.1, 95% CI=-1.8, 2.0). There was no evidence of any differences in secondary outcomes. Costs of direct care were similar in the two groups. CONCLUSIONS: The results suggest that treating people with borderline personality disorder with lamotrigine is not a clinically effective or cost-effective use of resources.

Lamotrigine for people with borderline personality disorder: a RCT.

BACKGROUND: No drug treatments are currently licensed for the treatment of borderline personality disorder (BPD). Despite this, people with this condition are frequently prescribed psychotropic medications and often with considerable polypharmacy. Preliminary studies have indicated that mood stabilisers may be of benefit to people with BPD. OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of lamotrigine for people with BPD. DESIGN: A two-arm, double-blind, placebo-controlled individually randomised trial of lamotrigine versus placebo. Participants were randomised via an independent and remote web-based service using permuted blocks and stratified by study centre, the severity of personality disorder and the extent of hypomanic symptoms. SETTING: Secondary care NHS mental health services in six centres in England. PARTICIPANTS: Potential participants had to be aged ≥ 18 years, meet diagnostic criteria for BPD and provide written informed consent. We excluded people with coexisting psychosis or bipolar affective disorder, those already taking a mood stabiliser, those who spoke insufficient English to complete the baseline assessment and women who were pregnant or contemplating becoming pregnant. INTERVENTIONS: Up to 200 mg of lamotrigine per day or an inert placebo. Women taking combined oral contraceptives were prescribed up to 400 mg of trial medication per day. MAIN OUTCOME MEASURES: Outcomes were assessed at 12, 24 and 52 weeks after randomisation. The primary outcome was the total score on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) at 52 weeks. The secondary outcomes were depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment and adverse events. Higher scores on all measures indicate poorer outcomes. RESULTS: Between July 2013 and October 2015 we randomised 276 participants, of whom 195 (70.6%) were followed up 52 weeks later. At 52 weeks, 49 (36%) of those participants prescribed lamotrigine and 58 (42%) of those prescribed placebo were taking it. At 52 weeks, the mean total ZAN-BPD score was 11.3 [standard deviation (SD) 6.6] among those participants randomised to lamotrigine and 11.5 (SD 7.7) among those participants randomised to placebo (adjusted mean difference 0.1, 95% CI -1.8 to 2.0; p = 0.91). No statistically significant differences in secondary outcomes were seen at any time. Adjusted costs of direct care for those prescribed lamotrigine were similar to those prescribed placebo. LIMITATIONS: Levels of adherence in this pragmatic trial were low, but greater adherence was not associated with better mental health. CONCLUSIONS: The addition of lamotrigine to the usual care of people with BPD was not found to be clinically effective or provide a cost-effective use of resources. FUTURE WORK: Future research into the treatment of BPD should focus on improving the evidence base for the clinical effectiveness and cost-effectiveness of non-pharmacological treatments to help policy-makers make better decisions about investing in specialist treatment services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365. FUNDING: Funding for this trial was provided by the Health Technology Assessment programme of the National Institute for Health Research (NIHR) and will be published in full in Health Technology Assessment; Vol. 22, No. 17. See the NIHR Journals Library website for further project information. The Imperial Biomedical Research Centre Facility, which is funded by NIHR, also provided support that has contributed to the research results reported within this paper. Part of Richard Morriss' salary during the project was paid by NIHR Collaboration for Leadership in Applied Health Research and Care East Midlands.

Cognitive-behaviour therapy for health anxiety in medical patients (CHAMP): a randomised controlled trial with outcomes to 5 years.

BACKGROUND: Health anxiety is an under-recognised but frequent cause of distress that is potentially treatable, but there are few studies in secondary care. OBJECTIVE: To determine the clinical effectiveness and cost-effectiveness of a modified form of cognitive-behaviour therapy (CBT) for health anxiety (CBT-HA) compared with standard care in medical outpatients. DESIGN: Randomised controlled trial. SETTING: Five general hospitals in London, Middlesex and Nottinghamshire. PARTICIPANTS: A total of 444 patients aged 16-75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics who scored ≥ 20 points on the Health Anxiety Inventory (HAI) and satisfied diagnostic requirements for hypochondriasis. Those with current psychiatric disorders were excluded, but those with concurrent medical illnesses were not. INTERVENTIONS: Cognitive-behaviour therapy for health anxiety - between 4 and 10 1-hour sessions of CBT-HA from a health professional or psychologist trained in the treatment. Standard care was normal practice in primary and secondary care. MAIN OUTCOME MEASURES: Primary - researchers masked to allocation assessed patients at baseline, 3, 6, 12, 24 months and 5 years. The primary outcome was change in the HAI score between baseline and 12 months. Main secondary outcomes - costs of care in the two groups after 24 and 60 months, change in health anxiety (HAI), generalised anxiety and depression [Hospital Anxiety and Depression Scale (HADS)] scores, social functioning using the Social Functioning Questionnaire and quality of life using the EuroQol-5 Dimensions (EQ-5D), at 6, 12, 24 and 60 months, and deaths over 5 years. RESULTS: Of the 28,991 patients screened over 21 months, 5769 had HAI scores of ≥ 20 points. Improvement in HAI scores at 3 months was significantly greater in the CBT-HA group (mean number of sessions = 6) than in the standard care, and this was maintained over the 5-year period (overall p < 0.0001), with no loss of efficacy between 2 and 5 years. Differences in the generalised anxiety (p = 0.0018) and depression scores (p = 0.0065) on the HADS were similar in both groups over the 5-year period. Gastroenterology and cardiology patients showed the greatest CBT gains. The outcomes for nurses were superior to those of other therapists. Deaths (n = 24) were similar in both groups; those in standard care died earlier than those in CBT-HA. Patients with mild personality disturbance and higher dependence levels had the best outcome with CBT-HA. Total costs were similar in both groups over the 5-year period (£12,590.58 for CBT-HA; £13,334.94 for standard care). CBT-HA was not cost-effective in terms of quality-adjusted life-years, as measured using the EQ-5D, but was cost-effective in terms of HAI outcomes, and offset the cost of treatment. LIMITATIONS: Many eligible patients were not randomised and the population treated may not be representative. CONCLUSIONS: CBT-HA is a highly effective treatment for pathological health anxiety with lasting benefit over 5 years. It also improves generalised anxiety and depressive symptoms more than standard care. The presence of personality abnormality is not a bar to successful outcome. CBT-HA may also be cost-effective, but the high costs of concurrent medical illnesses obscure potential savings. This treatment deserves further research in medical settings. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14565822. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 50. See the NIHR Journals Library website for further project information.

Loss of relational continuity of care in schizophrenia: associations with patient satisfaction and quality of care.

BACKGROUND: Users of mental health service are concerned about changes in clinicians providing their care, but little is known about their impact. AIMS: To examine associations between changes in staff, and patient satisfaction and quality of care. METHOD: A national cross-sectional survey of 3379 people aged 18 or over treated in secondary care for schizophrenia or schizoaffective disorder. RESULTS: Nearly 41.9% reported at least one change in their key worker during the previous 12 months and 10.5% reported multiple changes. Those reporting multiple changes were less satisfied with their treatment and less likely to report having a care plan, knowing how to obtain help when in a crisis or to have had recommended physical health assessments. CONCLUSIONS: Frequent changes in staff providing care for people with psychosis are associated with poorer quality of care. Greater efforts need to be made to protect relational continuity of care for such patients. DECLARATION OF INTEREST: M.J.C. was co-chair of the expert advisory group on the NICE quality standard on Service User Experience in Adult Mental Health. S.J.C. has previously been a member of the Health and Social Care Board Northern Ireland Formulary Committee. D.S. received a speaker's fee from Janssen Cilag in 2011. He is a topic expert on NICE guideline for psychosis and schizophrenia in children and young people and a board member of National Collaborating Centre for Mental Health. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Impact of personality status on the outcomes and cost of cognitive-behavioural therapy for health anxiety.

BACKGROUND: Health anxiety, hypochondriasis and personality disturbance commonly coexist. The impact of personality status was assessed in a secondary analysis of a randomised controlled trial (RCT). AIMS: To test the impact of personality status using ICD-11 criteria on the clinical and cost outcomes of treatment with cognitive-behavioural therapy for health anxiety (CBT-HA) and standard care over 2 years. METHOD: Personality dysfunction was assessed at baseline in 444 patients before randomisation and independent assessment of costs and outcomes made on four occasions over 2 years. RESULTS: In total, 381 patients (86%) had some personality dysfunction with 184 (41%) satisfying the ICD criteria for personality disorder. Those with no personality dysfunction showed no treatment differences (P = 0.90) and worse social function with CBT-HA compared with standard care (P<0.03) whereas all other personality groups showed greater improvement with CBT-HA maintained over 2 years (P<0.001). Less benefit was shown in those with more severe personality disorder (P<0.05). Costs were less with CBT-HA except for non-significant greater differences in those with moderate or severe personality disorder. CONCLUSIONS: The results contradict the hypothesis that personality disorder impairs response to CBT in health anxiety in both the short and medium term.

Quality of physical health care among patients with personality disorder.

OBJECTIVE: To investigate the assessment and treatment of physical health in patients with personality disorder and compare this to the care received in schizophrenia. METHOD: We collected data from a random sample of 246 patients with personality disorder on monitoring and intervention for seven key aspects of physical health. We compared the results with those from a random sample with schizophrenia. RESULTS: In our sample, 160 (65%) people had the diagnosis of emotionally unstable personality disorder. In total, 104 (42.3%) people with personality disorder were being prescribed antipsychotic medication; 23 (9.3%) participants had all seven aspects of physical health recorded. Alcohol was most frequently recorded (76%); BMI (38.6%), blood glucose (25.2%) and blood cholesterol (20.7%) were less likely to be recorded. Interventions were not given to all those requiring them. Compared to people with schizophrenia, a lower proportion had evidence of assessment of smoking, illicit drug use, blood glucose and blood lipid levels. Smoking cessation advice was more likely to be offered to people with schizophrenia (difference = 29.4%, 95% CI = 12.5 to 44.7). CONCLUSION: Physical health is under-assessed and under-treated in patients with personality disorder. Medical staff must do more to help tackle increased morbidity among this group.

Lamotrigine versus inert placebo in the treatment of borderline personality disorder: study protocol for a randomized controlled trial and economic evaluation.

BACKGROUND: People with borderline personality disorder (BPD) experience rapid and distressing changes in mood, poor social functioning and have high rates of suicidal behaviour. Several small scale studies suggest that mood stabilizers may produce short-term reductions in symptoms of BPD, but have not been large enough to fully examine clinical and cost-effectiveness. METHODS/DESIGN: A two parallel-arm, placebo controlled randomized trial of usual care plus either lamotrigine or an inert placebo for people aged over 18 who are using mental health services and meet diagnostic criteria for BPD. We will exclude people with comorbid bipolar affective disorder or psychosis, those already taking a mood stabilizer, those who speak insufficient English to complete the baseline assessment and women who are pregnant or contemplating becoming pregnant. Those meeting inclusion criteria and provide written informed consent will be randomized to up to 200mg of lamotrigine per day or an inert placebo (up to 400mg if taking combined oral contraceptives). Participants will be randomized via a remote web-based system using permuted stacked blocks stratified by study centre, severity of personality disorder, and level of bipolarity. Follow-up assessments will be conducted by masked researchers 12, 24 weeks, and 52 weeks after randomization. The primary outcome is the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD). The secondary outcomes are depressive symptoms, deliberate self-harm, social functioning, health-related quality of life, resource use and costs, side effects of treatment, adverse events and withdrawal of trial medication due to adverse effects. The main analyses will use intention to treat without imputation of missing data. The economic evaluation will take an NHS/Personal Social Services perspective. A cost-utility analysis will compare differences in total costs and differences in quality of life using QALYs derived from the EQ-5D. DISCUSSION: The evidence base for the use of pharmacological treatments for people with borderline personality disorder is poor. In this trial we will examine the clinical and cost-effectiveness of lamotrigine to assess what if any impact offering this has on peoples' mental health, social functioning, and use of other medication and other resources. TRIAL REGISTRATION: Current Controlled Trials ISRCTN90916365 (registered 01/08/2012).

The clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial.

OBJECTIVES: To examine the clinical and cost-effectiveness of brief advice for excessive alcohol consumption among people who attend sexual health clinics. METHODS: Two-arm, parallel group, assessor blind, pragmatic, randomised controlled trial. 802 people aged 19 years or over who attended one of three sexual health clinics and were drinking excessively were randomised to either brief advice or control treatment. Brief advice consisted of feedback on alcohol and health, written information and an offer of an appointment with an Alcohol Health Worker. Control participants received a leaflet on health and lifestyle. The primary outcome was mean weekly alcohol consumption during the previous 90 days measured 6 months after randomisation. The main secondary outcome was unprotected sex during this period. RESULTS: Among the 402 randomised to brief advice, 397 (99%) received it. The adjusted mean difference in alcohol consumption at 6 months was -2.33 units per week (95% CI -4.69 to 0.03, p=0.053) among those in the active compared to the control arm of the trial. Unprotected sex was reported by 154 (53%) of those who received brief advice, and 178 (59%) controls (adjusted OR=0.89, 95% CI 0.63 to 1.25, p=0.496). There were no significant differences in costs between study groups at 6 months. CONCLUSIONS: Introduction of universal screening and brief advice for excessive alcohol use among people attending sexual health clinics does not result in clinically important reductions in alcohol consumption or provide a cost-effective use of resources. TRIAL REGISTRATION NUMBER: Current Controlled Trials ISRCTN 99963322.

Preliminary studies of the ICD-11 classification of personality disorder in practice.

OBJECTIVE: This study aims to compare ICD-10 and putative ICD-11 classifications of personality disorder in different clinical populations. DESIGN: Prospective recording of ICD-10 and ICD-11 personality disorder classifications was carried out in (1) an anxious medical population, (2) an acute psychiatric in-patient population and (3) a retrospective recording of a mixed anxiety depression cohort in which all baseline data were scored from baseline information using the ICD-11 classification and compared with the original ICD-10 assessments. METHOD: Comparison of ICD-10 and ICD-11 prevalence of personality disorder in each population was carried out. RESULTS: Data from 722 patients were recorded. Using the ICD-10 criteria, the prevalence of generic personality disorder was 33.8% compared with 40.4% using the ICD-11 ones (χ2 = 6.7; P < 0.01), with 103 (14.3%) discordant assessments. Using the severity definitions in ICD-11, 34.3% of patients had personality difficulty. Severity level varied greatly by population; severe personality disorder was five times more common in the inpatient group. The four domain traits originally denoted as qualifying severity in ICD-11, negative affective, dissocial, anankastic and detached, were linked to anxious, borderline, dissocial, anankastic and schizoid personality disorders in ICD-10. Many patients had pathology in two or more domains. CONCLUSIONS: The ICD-11 classification of personality disorder yields somewhat higher levels of personality dysfunction than ICD-10, possibly because the age range for the onset of diagnosis is now flexible. The range of severity levels make the classification more useful than ICD-10 in clinical practice as it identifies the greater pathology necessary for intervention.

The clinical effectiveness and cost-effectiveness of brief intervention for excessive alcohol consumption among people attending sexual health clinics: a randomised controlled trial (SHEAR).

BACKGROUND: Excessive use of alcohol is associated with poor sexual health, but the clinical effectiveness and cost-effectiveness of brief alcohol intervention in this setting has not been investigated. OBJECTIVE: To examine the effects and cost-effectiveness of brief intervention for excessive alcohol consumption among people who attend sexual health clinics. DESIGN: A two-arm, parallel-group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by clinic. SETTING: Study participants were recruited from three sexual health clinics in central and west London. PARTICIPANTS: For inclusion, potential participants had to be aged ≥ 19 years, drink excessive alcohol according to the Modified-Single Alcohol Screening Question, and be willing to provide written informed consent. We excluded those who were unable to communicate in English sufficiently well to complete the baseline assessment and those who could not provide contact details for the follow-up assessment. INTERVENTIONS: Brief advice was delivered by the treating clinician and comprised feedback on the possible health consequences of excessive drinking, a discussion of whether the participant's clinic attendance was linked to current alcohol use, written information on alcohol and health and an offer of an appointment with an alcohol health worker (AHW). Appointments with AHWs took place either in person or by telephone, lasted up to 30 minutes, and used the 'FRAMES' (Feedback about the adverse effects of alcohol, an emphasis on personal Responsibility for changing drinking behaviour, Advice about alcohol consumption, a Menu of options for further help and advice, an Empathic stance towards the patient and an emphasis on Self-efficacy) approach. Those in the control arm of the trial were offered a copy of a leaflet providing general information on health and lifestyle. MAIN OUTCOME MEASURES: Outcomes were assessed 6 months after randomisation. The primary outcome was mean weekly alcohol consumption during the previous 90 days. The main secondary outcome was unprotected sex during this period. RESULTS: Eight hundred and two people were recruited to the study of whom 592 (74%) were followed up 6 months later. Among 402 participants who were randomised to brief intervention, 397 (99%) received brief advice from the treating clinician and 81 (20%) also received input from an AHW. The adjusted mean difference in alcohol consumption after 6 months was -2.33 units per week [95% confidence interval (CI) -4.69 to 0.03 units per week, p = 0.053] for those in the active arm compared with the control arm. Unprotected sex was reported by 154 (53%) of those who received brief intervention and by 178 (59%) of controls (adjusted odds ratio 0.89, 95% CI 0.63 to 1.25, p = 0.496). Participants randomised to brief intervention reported drinking a mean of 10.4 units of alcohol per drinking day compared with 9.3 units among control participants (difference 1.10, 95% CI 0.29 to 1.96, p = 0.009). We found no statistically significant differences in other outcomes. Brief intervention (brief advice and input from an AHW) cost on average £12.60 per person to deliver and did not appear to provide a cost-effective use of resources. CONCLUSIONS: Introduction of universal screening and brief intervention for excessive alcohol use among people who attend sexual health clinics does not result in clinically important reductions in alcohol consumption or provide a cost-effective use of resources. While people attending sexual health clinics may want to achieve better sexual health, attempts to reduce alcohol consumption may not be seen by them as a necessary means of trying to achieve this aim. TRIAL REGISTRATION: This trial is registered as ISRCTN 99963322. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 18, No. 30. See the NIHR Journals Library website for further project information.

Relationship between price paid for off-trade alcohol, alcohol consumption and income in England: a cross-sectional survey.

AIMS: In order to examine the potential impact of an increase in the minimum price per unit of alcohol to 50 pence ($0.78), we examined drinking patterns and household incomes of people who purchase alcohol in England at above and below this price. METHODS: Cross-sectional survey of 515 members of the public in seven towns and cities in the south of England. The primary outcome was whether the participant had purchased alcohol at <50 p/unit. The main exposures were annual household income and alcohol consumption, measured using the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C). RESULTS: The median price paid per unit of alcohol was 53.1 pence (range 16.4-297.0 pence). Those buying alcohol at <50 p/unit had a mean AUDIT-C score of 6.2 compared with 5.5 among those buying alcohol at above this price. The odds ratio (OR) of a person on low income with high-risk drinking purchasing alcohol at <50 p/unit was 1.29 [95% confidence interval (CI) = 0.82-1.79] compared with all other study participants. The OR of a person on low income with low-risk drinking purchasing alcohol below this price was 0.51 (95% CI = 0.30-0.87) compared with all other participants. CONCLUSIONS: These data suggest that an increase in the minimum price of alcohol to 50 pence price per unit is only likely to disproportionately affect people on low incomes if their alcohol consumption is excessive.