Full Title - The clinical and cost effectiveness of quetiapine for people with borderline personality disorder: A pragmatic, double-blind, placebo-controlled, randomised trial. Short Title - Quetiapine Effectiveness Study in Borderline Personality Disorder (QUEST).

Research question - What is the clinical effectiveness, cost-effectiveness, safety and tolerability of quetiapine for treating people with borderline personality disorder (BPD)?

Background - BPD is a severe mental health condition characterised by mood instability, recurrent suicidal behaviour and impaired interpersonal functioning. BPD is common among people in contact with mental health services and it's estimated that the cost of services for people with personality disorder is over £700,000,000 per annum. NICE recommend psychological treatments for people with BPD but many people, especially those with the most severe disorder, are unable or unwilling to make use of them.

No drugs are currently licensed or recommended for the treatment of people with BPD, yet large scale audits show that over 50% of people with BPD are taking antipsychotic drugs long-term. The most commonly prescribed antipsychotic drug in England is quetiapine. Systematic reviews of antipsychotic trials for BPD find that quetiapine has the most promising evidence but the only published trial of quetiapine to date was small (n = 95) and examined short-term effects (8 weeks) and larger scale studies with longer follow-up periods are needed.

Aims and objectives – i) To test whether adding quetiapine to treatment as usual (TAU) improves the mental health of people with BPD and/or improves social and occupational functioning, quality of life and/or reduces the incidence of suicidal behaviour; ii) To compare the incidence of side-effects, between quetiapine and placebo; iii) To examine the cost, cost-effectiveness and cost-utility of adding quetiapine to TAU for adults with BPD.

Methods - A multi-centre, two-arm, parallel group, double-blind, placebo-controlled, trial. The trial will undertake a clinical and economic evaluation and examine the impact of adding quetiapine to TAU for adults with BPD over a twelve-month period. There will be an internal pilot phase, with pre-defined Stop/Go criteria.

Double-blinded assessments will take place at 3, 6, 9 and 12 months. Participants will be recruited from in-patient and out-patient secondary care mental health services across six NHS Mental Health Trusts and to maximise generalisability of study findings we have kept our inclusion criteria broad and limited our exclusion criteria.

Trial medication will be generic quetiapine (slow release) at a target dose of 150 mg, with higher or lower doses allowed according to clinical response and tolerability. No restrictions will be imposed on the use of other treatments, except that those who remain in the trial will not be prescribed antipsychotics (aside from trial medication).

The primary outcome is symptoms of BPD measured at 12 months and we aim to recruit 270 participants.

Timelines for delivery - Trial duration 53 months. Study set-up 8 months; recruitment and follow-up 42 months duration (average rate of 10 participants per month); analysis and write-up 3 months.

Anticipated impact and dissemination - Obtaining high quality evidence for the clinical and cost-effectiveness of quetiapine for BPD will provide clinicians and patients with long-term information based on a pragmatic trial design. We will publish in high impact journals and use NIHR platforms with PPIE input and present at service user regional meetings and events.