The clinical effectiveness and cost-effectiveness of clozapine for hospitalized patients with severe borderline personality disorder (CALMED study): a randomized placebo-controlled trial

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Ther Adv Psychopharmacol. 2022 Apr 29;12:20451253221090832. doi: 10.1177/20451253221090832. eCollection 2022.

ABSTRACT

BACKGROUND: Case series data suggest that clozapine may benefit hospitalized patients with borderline personality disorder (BPD), but no randomized trials have been conducted.

METHODS: Multicenter, double-blind, placebo-controlled trial. Our aim was to recruit 222 hospitalized patients with severe borderline personality disorder aged 18 years or older who had not responded to other antipsychotic medications. We randomized participants in a 1:1 ratio to receive up to 400 mg clozapine daily or an inert placebo using a web-based remote randomization service. The primary outcome was the total score on the Zanarini 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 (mITT) analysis restricted to people who took one or more doses of the test drug, using a general linear model fitted at 6 months adjusted for baseline score, the group of attribution and site.

RESULTS: The study ended prematurely 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 which 21 (72%) were included in the mITT analysis. At 6 months, 11 (73%) of those assigned to clozapine and 6 (43%) of those assigned to placebo were still taking the trial drug. The 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 the groups.

INTERPRETATION: We did not recruit enough participants to test the main hypothesis. The study results highlight problems in conducting placebo-controlled trials of clozapine and in the use of clozapine for people with BPD outside of specialized inpatient mental health units.

TEST RECORD: ISRCTN18352058. https://doi.org/10.1186/ISRCTN18352058.

PMID:35510087 | PMC:PMC9058570 | DOI: 10.1177/20451253221090832

Sara H. Byrd