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

Background Anxiety about COVID-19 is common. For most people this is an appropriate response to the loss of livelihoods and loved-ones, disruptions to social networks, and uncertainty about the future. However, for others these anxieties relate to contracting the virus itself, a phenomenon termed COVID anxiety. Little is known about the characteristics of people with severe COVID anxiety or the impact it has on their daily lives. Methods We conducted a two-phase cross-sectional survey of people aged 18 or over who were living in United Kingdom, self-identified as anxious about COVID-19, and had a score of ≥9 on the Coronavirus Anxiety Scale. We recruited participants nationally through online adverts and locally via primary care services in London. Data on demographic and clinical factors were used in multiple regression modelling to examine the greatest contributors to functional impairment, poor health-related quality of life and protective behaviours in this sample of individuals with severe COVID anxiety. Results We recruited 306 people with severe COVID anxiety between January and September 2021. Most were female (n = 246, 81.2%); they had a median age of 41 (range = 18–83). The majority of participants also had generalised anxiety (n = 270, 91.5%), depression (n = 247, 85.5%), and a quarter (n = 79, 26.3%) reported a physical health condition which put them at increased risk of hospitalisation with COVID-19. Half had severe social dysfunction (n = 151, 52.4%). One in ten reported never leaving their home, one in three washed all items brought into their house, one in five washed their hands constantly, and one in five of those with children reported not sending them to school because of fears of COVID-19. Increasing co-morbid depressive symptoms best explained functional impairment and poor quality of life after controlling for other factors. Conclusions This study highlights the high degree of co-occuring mental health problems, and the extent of functional impairment and poor health-related quality of life among people with severe COVID anxiety. Further research is needed to establish the course of severe COVID anxiety as the pandemic progresses, and steps that can be taken to support people who experience this distress.

Background: Anxiety about COVID-19 is common. For most people this is an appropriate response to the loss of livelihoods and loved-ones, disruptions to social networks, and uncertainty about the future. However, for others these anxieties relate to contracting the virus itself. Little is known about the characteristics of people with severe COVID anxiety or the impact it has on their daily lives. Methods: We conducted a two-phase cross-sectional survey of people aged 18 or over who were living in United Kingdom, self-identified as anxious about COVID-19, and had a score of ≥9 on the Coronavirus Anxiety Scale. We recruited participants nationally through online adverts and locally via primary care services in London. Data on demographic and clinical factors were used in multiple regression modelling to examine the greatest contributors to functional impairment, poor health-related quality of life and protective behaviours in this sample of individuals with severe COVID anxiety. Results: We recruited 306 people with severe COVID anxiety between January and September 2021. Most were female (n = 246, 81.2%); they had a median age of 40 (range = 18-83). The majority of participants also had generalised anxiety (n = 270, 91.5%), depression (n = 247, 85.5%), and a quarter (n = 79, 26.3%) reported a physical health condition which put them at increased risk of hospitalisation with COVID-19. Half had severe social dysfunction (n = 151, 52.4%). One in ten reported never leaving their home, one in three washed all items brought into their house, one in five washed their hands constantly, and one in five of those with children reported not sending them to school because of fears of COVID-19. Increasing co-morbid depressive symptoms best explained functional impairment and poor quality of life after controlling for other factors. Conclusions: This study highlights the high degree of co-occuring mental health problems, and the extent of functional impairment and poor health-related quality of life among people with severe COVID anxiety. Further research is needed to establish the course of severe COVID anxiety as the pandemic progresses, and steps that can be taken to support people who experience this distress.

Introduction Some people are so anxious about COVID-19 that it impairs their functioning. However, little is known about the course of severe COVID-19 anxiety or what can be done to help people who experience it. Methods and analysis Cohort study with a nested feasibility trial with follow-up at 3 and 6 months. We recruited 306 people who were aged 18 and over, lived in the UK and had severe COVID-19 anxiety (indicated by a score of 9 or more on the Coronavirus Anxiety Scale (CAS)). To take part in the nested feasibility trial, participants also had to have a score of 20 or more on the Short Health Anxiety Inventory. We excluded people from the trial if they had had COVID-19 within the previous 4 weeks, if they were currently self-isolating or if they were already receiving psychological treatment. We publicised the study nationally through adverts, social media and posts on message boards. We also recruited participants via clinicians working in primary and secondary care NHS services in London. All those in the active arm will be offered 5–10 sessions of remotely delivered modified cognitive–behavioural therapy for health anxiety (CBT-HA). We will examine the proportion of participants who remain above threshold on the CAS at 3 and 6 months and factors that influence levels of COVID-19 anxiety over 6 months using mixed effects logistic regression. The key feasibility metrics for the nested trial are the level of uptake of CBT-HA and the rate of follow-up. Ethics and dissemination Approved by Leicester Central Research Ethics Committee (reference: 20/EM/0238). The results of the study will be published in peer-reviewed scientific journals. Trial registration number NCT14973494.