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.

Experiences of women in secure care who have been prescribed clozapine for borderline personality disorder.

BACKGROUND: Clozapine is an atypical antipsychotic medicine which can cause significant side-effects. It is often prescribed off-license in severe cases of borderline personality disorder contrary to national treatment guidelines. Little is known about the experiences of those who take clozapine for borderline personality disorder. We explored the lived-experience of women in secure inpatient care who were prescribed clozapine for borderline personality disorder. FINDINGS: Adult females (N = 20) participated in audio-taped semi-structured interviews. Transcripts were subject to thematic analysis. The central themes related to evaluation, wellbeing, understanding and self-management; for many, their subjective wellbeing on clozapine was preferred to prior levels of functioning and symptomatology, sometimes profoundly so. The negative and potentially adverse effects of clozapine were explained as regrettable but relatively unimportant. CONCLUSIONS: When psychological interventions are, at least initially, ineffective then clozapine treatment is likely to be evaluated positively by a group of women with borderline personality disorder in secure care despite the potential disadvantages.

A case series of clozapine for borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a common, debilitating disorder for which the evidence base for treatment is modest. This case series aimed to explore preliminary evidence of clozapine's effectiveness for patients with severe BPD. METHODS: We examined the case notes of 22 female inpatients with a primary diagnosis of BPD who had started treatment with clozapine. Baseline routine clinical data were extracted from the records and at 6 monthly intervals thereafter, up to a maximum of 18 months after starting treatment. Patients also were interviewed about their experiences. RESULTS: We found evidence for a beneficial effect of clozapine across several clinical domains. Symptom severity, need for enhanced observations, use of additional medication, and the number of aggressive incidents all significantly improved after clozapine. The greatest improvements appeared within the first 6 months of initiating treatment. There also was a significant increase in weight. CONCLUSIONS: The results suggest that clozapine, with suitable health monitoring, may be beneficial for this clinical population. Larger, randomized, blinded, and controlled prospective studies are needed to confirm these findings.

The prevalence of personality disorder, its comorbidity with mental state disorders, and its clinical significance in community mental health teams.

BACKGROUND: Personality status is seldom assessed in community mental health teams except at a rudimentary level. This study challenges the assumption that this policy is either prudent or wise. AIMS: To measure the prevalence of personality disorder within community mental health teams and to investigate its relationship to mental state disorders and overall pathology. METHOD: A cross-sectional survey of 2,528 of 2,567 psychiatric patients (98.5%) managed by community mental health teams in four urban settings in the UK in which diagnoses of personality and mental state pathology were assessed separately. Of these, a sample of 400 was interviewed, with a 70.5% completion rate for more in depth information. RESULTS: In total, 40% of all patients in secondary care suffered from at least one personality disorder. Regression modelling showed personality pathology accounted for a greater degree of global psychopathology than psychosis, alcohol or drug dependence, but was associated with anxiety disorders. CONCLUSION: Comorbid personality pathology contributes greatly to overall psychopathology in secondary psychiatric care. It should be both recognised and managed.